Abstract
Background
Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.
Methods
In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.
Findings
Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).
Interpretation
In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication.
Funding
UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Introduction
A substantial proportion of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop a respiratory illness requiring hospital care, which can progress to critical illness with hypoxic respiratory failure requiring prolonged ventilatory support. Among patients with COVID-19 admitted to UK hospitals in the first wave of the epidemic, the case fatality rate was greater than 26%, and in excess of 37% in patients requiring invasive mechanical ventilation.1
In patients with severe COVID-19, the host immune response is thought to play a key role in driving an acute pneumonic process with diffuse alveolar damage, inflammatory infiltrates, and microvascular thrombosis.2 The beneficial effects of dexamethasone and other corticosteroids in patients with hypoxic lung damage suggest that other drugs that suppress or modulate the immune system might provide additional improvements in clinical outcomes.3, 4
Macrolide antibiotics, such as azithromycin, clarithromycin, and erythromycin, are widely available and their safety is well established. In addition to antibacterial properties, they are known to have immunomodulatory activity, decreasing production of pro-inflammatory cytokines and inhibiting neutrophil activation.5, 6, 7 They are widely used both in bacterial pneumonia due to their antimicrobial activity and in chronic inflammatory lung disease due to their immunomodulatory effects.8, 9, 10 In addition, azithromycin has in-vitro antiviral activity against a range of viruses and has been reported to inhibit SARS-CoV-2 replication in Vero cells and human epithelial cells at concentrations (50% effective concentration 2·12 μM) that are achieved in lung tissue with a dose of 500 mg once per day.11, 12, 13
Research in context.
Evidence before this study
Azithromycin is commonly used in patients with COVID-19 for either its antimicrobial, anti-inflammatory, or purported antiviral activity. We searched MEDLINE, Embase, bioRxiv, medRxiv, and the WHO International Clinical Trials Registry Platform, from Sept 1, 2019, up to Nov 12, 2020, for completed clinical trials published in any language evaluating the effect of azithromycin or other macrolide antibiotics in patients with COVID-19. We used the search terms (“COVID.mp.” OR “COVID-19.mp.” OR “SARS-CoV-2.mp.” OR “2019-nCoV.mp.” OR “coronavirus/” or “CORONAVIRUS.mp.”) AND (“azithromycin.mp.” OR “macrolide.mp.”), filtered by randomised controlled trials according to validated filters. We identified three published randomised clinical trials (two at low risk of bias and one with some concerns due to limited information on the randomisation process) that compared the effect of azithromycin (500 mg once a day) to usual care in patients admitted to hospital with COVID-19. In all three studies, all patients also received hydroxychloroquine. None of the three studies, which in combination included 1223 patients, found differences in mortality or odds of clinical improvement; however, all were underpowered to exclude moderate but clinically relevant treatment effects.
Added value of this study
The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial is a large, randomised trial evaluating the effect of azithromycin monotherapy on mortality in patients admitted to hospital with COVID-19. We found no significant difference between the azithromycin group and the usual care group in 28-day all-cause mortality, the probability of discharge alive within 28 days, or, among the patients who were not receiving invasive mechanical ventilation at randomisation, the probability of progressing to the composite outcome of invasive mechanical ventilation or death. We saw no evidence of clinical benefit of azithromycin in any patient subgroup.
Implications of all the available evidence
Azithromycin should not be used to treat patients admitted to hospital with COVID-19 unless there is a clear antimicrobial indication.
The use of macrolides in influenza-associated pneumonia has been associated with a faster reduction in inflammatory cytokines and, in combination with naproxen, decreased mortality.14, 15, 16 However, randomised trials have so far not shown convincing clinical benefit of macrolides in COVID-19.17, 18, 19 Here, we report the results of a randomised controlled trial of azithromycin in which we aimed to assess whether azithromycin improves clinical outcomes in patients admitted to hospital with COVID-19.
Methods
Study design and participants
The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial is an investigator-initiated, individually randomised, controlled, open-label, adaptive platform trial to evaluate the effects of potential treatments in patients admitted to hospital with COVID-19. Details of the trial design and results for other possible treatments (dexamethasone, hydroxychloroquine, and lopinavir–ritonavir) have been published previously.3, 20, 21 The trial is underway at 176 hospitals in the UK (appendix pp 2–22), supported by the National Institute for Health Research (NIHR) Clinical Research Network. The trial is coordinated by the Nuffield Department of Population Health at the University of Oxford (Oxford, UK), the trial sponsor. The trial is done in accordance with the principles of the International Conference on Harmonisation–Good Clinical Practice guidelines and approved by the UK Medicines and Healthcare products Regulatory Agency and the Cambridge East Research Ethics Committee (20/EE/0101). The protocol, statistical analysis plan, and additional information are available on the study website. Although the azithromycin, dexamethasone, hydroxychloroquine, lopinavir–ritonavir, convalescent plasma, and tocilizumab groups have now been stopped, the trial continues to study the effects of REGN-COV2 (a combination of two monoclonal antibodies directed against SARS-CoV-2 spike glycoprotein), aspirin, and colchicine. Other treatments might be studied in future.
Patients admitted to hospital were eligible for the study if they had clinically suspected or laboratory confirmed SARS-CoV-2 infection and no medical history that might, in the opinion of the attending clinician, put the patient at substantial risk if they were to participate in the trial. Initially, recruitment was limited to patients aged at least 18 years, but from May 9, 2020, the age limit was removed. Patients with known prolonged QTc interval or hypersensitivity to a macrolide antibiotic and those already receiving chloroquine or hydroxychloroquine were excluded from random assignment between azithromycin and usual care.
Written informed consent was obtained from all patients, or a legal representative if they were too unwell or unable to provide consent.
Randomisation and masking
Baseline data were collected using a web-based case report form that included demographics, amount of respiratory support, major comorbidities, suitability of the study treatment for a particular patient, and treatment availability at the study site (appendix pp 23–25). Eligible and consenting patients were assigned to either usual standard of care or usual standard of care plus azithromycin or one of the other available RECOVERY treatment groups using web-based simple (unstratified) randomisation with allocation concealed until after randomisation (appendix pp 23–25). Randomisation to usual care was twice that of any of the active treatment groups the patient was eligible for (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). For some patients, azithromycin was unavailable at the hospital at the time of enrolment or a macrolide antibiotic was considered by the managing physician to be either definitely indicated or definitely contraindicated. These patients were excluded from the randomised comparison between azithromycin and usual care. Patients allocated to azithromycin were to receive azithromycin 500 mg by mouth, nasogastric tube, or intravenous injection once a day for 10 days or until discharge, if sooner. Allocated treatment was prescribed by the managing doctor. Azithromycin was supplied from routine National Health Service (NHS) stocks.
For eligible participants, factorial randomisations were introduced such that participants could simultaneously be randomly assigned to convalescent plasma versus REGN-COV2 versus usual care and to aspirin versus usual care (appendix pp 23–25). Within 21 days of initial random assignment, participants with evidence of hypoxia and inflammation could be additionally randomly assigned to tocilizumab versus usual care alone. Participants and local study staff were not masked to the allocated treatment. The steering committee, investigators, and all others involved in the trial were masked to the outcome data during the trial.
Procedures
A single online follow-up form was completed when participants were discharged from hospital, died, or at 28 days after randomisation, whichever occurred earliest (appendix pp 29–35). Information was recorded on adherence to allocated study treatment, receipt of other COVID-19 treatments, duration of admission, receipt of respiratory or renal support, and vital status (including cause of death). In addition, routine health-care and registry data were obtained, including information on vital status (with date and cause of death), discharge from hospital, receipt of respiratory support, or renal replacement therapy. Details of how this information was used to derive baseline characteristics and clinical outcomes are provided in the appendix (pp 112–31).
Outcomes
Outcomes were assessed at 28 days after randomisation, with further analyses specified at 6 months. The primary outcome was 28-day all-cause mortality. Secondary outcomes were time to discharge from hospital and, among patients not on invasive mechanical ventilation at randomisation, invasive mechanical ventilation (including extracorporeal membrane oxygenation) or death. Prespecified subsidiary clinical outcomes were cause-specific mortality, use of haemodialysis or haemofiltration, major cardiac arrhythmia (recorded in a subset), and receipt and duration of ventilation. Among those on invasive mechanical ventilation at randomisation, a subsidiary clinical outcome of successful cessation of invasive mechanical ventilation was defined as cessation within (and survival to) 28 days. Information on suspected serious adverse reactions was collected in an expedited manner to comply with regulatory requirements.
Statistical analysis
An intention-to-treat comparison was made between patients randomly assigned to azithromycin and those randomly assigned to usual care but for whom azithromycin was both available and suitable as a treatment. For the primary outcome of 28-day mortality, the log-rank observed minus expected statistic and its variance were used to both test the null hypothesis of equal survival curves (ie, the log-rank test) and to calculate the one-step estimate of the mortality rate ratio. We constructed Kaplan-Meier survival curves to display cumulative mortality over the 28-day period. We used similar methods to analyse time to hospital discharge and successful cessation of invasive mechanical ventilation, with patients who died in hospital right-censored on day 29. Median time to discharge was derived from Kaplan-Meier estimates. For the prespecified composite secondary outcome of invasive mechanical ventilation or death within 28 days (among those not receiving invasive mechanical ventilation at randomisation) and the subsidiary clinical outcomes of receipt of ventilation and use of haemodialysis or haemofiltration, the precise dates were not available and so the risk ratio was estimated instead.
Prespecified analyses of the primary outcome were done separately in six subgroups defined by characteristics at the time of random assignment: age, sex, ethnicity, days since symptom onset, level of respiratory support, and use of corticosteroids (appendix p 105). Observed effects within subgroup categories were compared using a χ2 test for heterogeneity or trend, in accordance with the prespecified analysis plan.
Estimates of rate and risk ratios are shown with 95% CIs. All p values are two-sided and are shown without adjustment for multiple testing. The full database is held by the study team who collected the data from study sites and did the analyses at the Nuffield Department of Population Health (University of Oxford, Oxford, UK).
As stated in the protocol, appropriate sample sizes could not be estimated when the trial was being planned at the start of the COVID-19 pandemic as it was unknown how large the epidemic would become (appendix p 26). As the trial progressed, the trial steering committee, whose members were unaware of the results of the trial comparisons, determined that sufficient patients should be enrolled to provide at least 90% power at a two-sided p value of 0·01 to detect a clinically relevant proportional reduction in the primary outcome of 20% between the two groups. Consequently, on Nov 27, 2020, the steering committee, masked to the results, closed recruitment to the azithromycin comparison as sufficient patients had been enrolled.
Analyses were done using SAS, version 9.4, and R, version 3.4.0. This trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.
Role of the funding source
The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Results
Between April 7 and Nov 27, 2020, 9433 (57%) of 16 442 patients enrolled in the RECOVERY trial were eligible to be randomly allocated to azithromycin (ie, azithromycin was available in the hospital at the time and the attending clinician was of the opinion that the patient had no known indication for or contraindication to azithromycin, figure 1 , appendix p 38). 2582 patients were randomly allocated to azithromycin and 5181 were randomly allocated to usual care, with the remainder being randomly allocated to one of the other treatment groups. The mean age of study participants in this comparison was 65·3 years (SD 15·7) and the median time since symptom onset was 8 days (IQR 5–11; table 1 ; appendix p 38).
Figure 1.
Trial profile
*Number recruited overall during the period that participants could be recruited into the azithromycin comparison. †Some patients were included in both of the below groups. ‡2506 (97%) of those allocated to azithromycin and 5054 (98%) of those allocated to usual care had a complete follow-up at time of analysis. §3993 patients were additionally randomly assigned to convalescent plasma versus REGN-COV2 versus control (1320 [51·1%] patients allocated to azithromycin versus 2673 [51·6%] patients allocated usual care) and 975 patients were additionally randomly assigned to aspirin versus usual care (323 [12·5%] patients allocated to azithromycin versus 652 [12·6%] patients allocated usual care). ¶Includes 198 (7·7%) of 2582 patients in the azithromycin group and 450 (8·7%) of 5181 patients in the usual care group allocated to tocilizumab.
Table 1.
Baseline characteristics
| Azithromycin (n=2582) | Usual care (n=5181) | ||
|---|---|---|---|
| Age, years | 65·4 (15·6) | 65·2 (15·7) | |
| <70* | 1508 (58%) | 3014 (58%) | |
| ≥70 to <80 | 615 (24%) | 1167 (23%) | |
| ≥80 | 459 (18%) | 1000 (19%) | |
| Sex | |||
| Men | 1604 (62%) | 3215 (62%) | |
| Women† | 978 (38%) | 1966 (38%) | |
| Ethnicity | |||
| White | 1961 (76%) | 3978 (77%) | |
| Black, Asian, and minority ethnic | 372 (14%) | 737 (14%) | |
| Unknown | 249 (10%) | 466 (9%) | |
| Number of days since symptom onset | 8 (5–11) | 8 (5–11) | |
| Number of days since admission to hospital | 2 (1–4) | 2 (1–4) | |
| Respiratory support received | |||
| No oxygen received | 490 (19%) | 918 (18%) | |
| Oxygen only‡ | 1940 (75%) | 3963 (76%) | |
| Invasive mechanical ventilation | 152 (6%) | 300 (6%) | |
| Previous diseases | |||
| Diabetes | 700 (27%) | 1433 (28%) | |
| Heart disease | 693 (27%) | 1350 (26%) | |
| Chronic lung disease | 621 (24%) | 1313 (25%) | |
| Tuberculosis | 3 (<1%) | 16 (<1%) | |
| HIV | 7 (<1%) | 22 (<1%) | |
| Severe liver disease§ | 45 (2%) | 65 (1%) | |
| Severe kidney impairment¶ | 155 (6%) | 334 (6%) | |
| Any of the above | 1507 (58%) | 3013 (58%) | |
| Use of corticosteroids | |||
| Yes | 1567 (61%) | 3171 (61%) | |
| No | 182 (7%) | 397 (8%) | |
| Not asked or missing‖ | 833 (32%) | 1613 (31%) | |
| SARS-CoV-2 test result | |||
| Positive | 2350 (91%) | 4743 (92%) | |
| Negative | 202 (8%) | 386 (7%) | |
| Unknown | 30 (1%) | 52 (1%) | |
Data are mean (SD), n (%), or median (IQR). SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.
Includes 26 children (<18 years).
Includes 25 pregnant women.
Includes non-invasive ventilation.
Defined as requiring ongoing specialist care.
Defined as estimated glomerular filtration rate <30 mL/min per 1·73 m2.
Information on use of corticosteroids was collected from June 18, 2020, onwards, following announcement of the results of the dexamethasone comparison from the RECOVERY trial.
The follow-up form was completed for 2506 (97%) patients in the azithromycin group and 5054 (98%) patients in the usual care group. Among patients with a completed follow-up form, 2269 (91%) allocated to azithromycin versus 68 (1%) allocated to usual care received at least one dose, and 2347 (94%) versus 837 (17%) received any macrolide antibiotic (appendix p 39). The median duration of treatment with azithromycin was 6 days (IQR 3–10). Use of other treatments for COVID-19 was similar among patients allocated azithromycin and among those allocated usual care, with more than half receiving a corticosteroid, about a quarter receiving remdesivir, about a fifth receiving convalescent plasma, and about a twelfth receiving tocilizumab or sarilumab (appendix p 39).
We observed no significant difference in the proportion of patients who met the primary outcome of 28-day mortality between the two randomised groups (561 [22%] of 2582 patients in the azithromycin group vs 1162 [22%] of 5181 patients in the usual care group; rate ratio 0·97, 95% CI 0·87–1·07; p=0·50; figure 2 ). We observed similar results across all prespecified subgroups (figure 3 ). In an exploratory analysis restricted to the 7093 (91%) of 7763 patients with a positive SARS-CoV-2 test result, the result was similar (rate ratio 0·95, 95% CI 0·86–1·06; p=0·38).
Figure 2.
Effect of allocation to azithromycin on 28-day mortality
Figure 3.
Effect of allocation to azithromycin on 28-day mortality by baseline characteristics
Subgroup-specific rate ratio estimates are represented by squares (with areas of the squares proportional to the amount of statistical information) and the lines through them correspond to 95% CIs. The ethnicity, days since onset, and use of corticosteroids subgroups exclude those with missing data, but these patients are included in the overall summary diamond. Information on use of corticosteroids was collected from June 18, 2020, onwards following announcement of the results of the dexamethasone comparison from the RECOVERY trial. *Includes patients receiving non-invasive ventilation.
Allocation to azithromycin was associated with a similar time until discharge from hospital alive as usual care (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) and a similar probability of discharge alive within 28 days (69% vs 68%, rate ratio 1·04, 95% CI 0·98–1·10; p=0·19; table 2 ). Among those not on invasive mechanical ventilation at baseline, the number of patients progressing to the prespecified composite secondary outcome of invasive mechanical ventilation or death among those allocated to azithromycin was similar to that among those allocated to usual care (25% vs 26%, risk ratio 0·95, 95% CI 0·87–1·03; p=0·24; table 2). Allowing for multiple testing in interpretation of the results, there was no evidence that the effect of allocation to azithromycin versus usual care on time until discharge from hospital alive or on invasive mechanical ventilation or death differed between prespecified subgroups of patients (appendix pp 43–44).
Table 2.
Effect of allocation to azithromycin on key study outcomes
| Azithromycin (n=2582) | Usual care (n=5181) | RR (95% CI) | p value | ||
|---|---|---|---|---|---|
| Primary outcome | |||||
| 28-day mortality | 561 (22%) | 1162 (22%) | 0·97 (0·87–1·07) | 0·50 | |
| Secondary outcomes | |||||
| Time to being discharged alive, days | 10 (5 to >28) | 11 (5 to >28) | NA | NA | |
| Discharged from hospital within 28 days | 1788 (69%) | 3525 (68%) | 1·04 (0·98–1·10) | 0·19 | |
| Receipt of invasive mechanical ventilation or death* | 603/2430 (25%) | 1273/4881 (26%) | 0·95 (0·87–1·03) | 0·24 | |
| Invasive mechanical ventilation | 211/2430 (9%) | 461/4881 (9%) | 0·92 (0·79–1·07) | 0·29 | |
| Death | 496/2430 (20%) | 1028/4881 (21%) | 0·97 (0·88–1·07) | 0·52 | |
| Subsidiary clinical outcomes | |||||
| Receipt of ventilation† | 226/1368 (17%) | 491/2705 (18%) | 0·91 (0·79–1·05) | 0·20 | |
| Non-invasive ventilation | 214/1368 (16%) | 467/2705 (17%) | 0·91 (0·78–1·05) | 0·19 | |
| Invasive mechanical ventilation | 57/1368 (4%) | 115/2705 (4%) | 0·98 (0·72–1·34) | 0·90 | |
| Successful cessation of invasive mechanical ventilation‡ | 54/152 (36%) | 96/300 (32%) | 1·15 (0·82–1·62) | 0·42 | |
| Use of haemodialysis or haemofiltration§ | 105/2539 (4%) | 224/5102 (4%) | 0·94 (0·75–1·18) | 0·61 | |
Data are n (%), median (IQR), or n/N (%), unless otherwise indicated. RR=rate ratio for the outcomes of 28-day mortality, hospital discharge, and successful cessation of invasive mechanical ventilation, and risk ratio for other outcomes. NA=not applicable.
Analyses exclude those on invasive mechanical ventilation at randomisation.
Analyses exclude those on any form of ventilation at randomisation.
Analyses restricted to those on invasive mechanical ventilation at randomisation.
Analyses exclude those on haemodialysis or haemofiltration at randomisation.
We found no significant differences in the prespecified subsidiary clinical outcomes of cause-specific mortality (appendix p 40), use of ventilation, successful cessation of invasive mechanical ventilation, or need for renal dialysis or haemofiltration (table 2). We observed no significant differences in the frequency of new cardiac arrhythmias (appendix p 41). There was one report of a serious adverse reaction believed to be related to azithromycin: a case of pseudomembranous colitis from which the patient recovered with standard treatment.
Discussion
The results of this large, randomised trial show that azithromycin is not an effective treatment for patients admitted to hospital with COVID-19. Allocation to azithromycin was not associated with reductions in mortality, duration of hospital stay, or the risk of being ventilated or dying for those not on ventilation at baseline. These results were consistent across the prespecified subgroups of age, sex, ethnicity, duration of symptoms before randomisation, level of respiratory support at randomisation, or use of corticosteroids at randomisation.
Azithromycin was proposed as a treatment for COVID-19 on the basis of its immunomodulatory activity.7 Although no major organisation or professional society has recommended the routine use of azithromycin in COVID-19 unless there is evidence of bacterial superinfection, it has nevertheless been used widely in patients with COVID-19, particularly in combination with hydroxychloroquine.22, 23, 24 Macrolides have long been suggested as potential therapies for inflammatory viral pneumonias but this hypothesis has been based on in-vitro, animal, and observational data, with very little evidence of benefit in clinical trials.13, 14, 15 The benefit of dexamethasone in patients with COVID-19 requiring respiratory support suggests that inflammation has a causal role in mortality.3 Noting that the absence of meaningful effect of azithromycin was consistent regardless of whether patients were also being given a corticosteroid or not, we conclude that the immunomodulatory properties of azithromycin are either insufficient in COVID-19.
Macrolides are commonly used to treat bacterial infections of the lower respiratory tract because of their activity against Gram-positive bacteria and atypical pathogens such as Mycoplasma pneumoniae and Legionella spp, as well as their excellent tissue penetration. More than 75% of patients with COVID-19 who were admitted to hospital in the UK during 2020 were prescribed antibiotics and the widespread clinical use of macrolides in COVID-19 is likely to be driven largely by concerns of bacterial superinfection rather than purported immunomodulatory activity.25 It is therefore important to highlight that in patients with moderate or severe COVID-19, who might be expected to have some burden of secondary bacterial lung infection, there was no observed clinical benefit of azithromycin use. This absence of meaningful effect could either reflect the relatively low rate of secondary bacterial infection in COVID-19 or the widespread use of β-lactam or other antibiotics, which might have abrogated any antibacterial benefit of allocation to azithromycin in this trial.26, 27 Our results showed that the addition of azithromycin to routine clinical care of patients admitted to hospital with COVID-19 confers no clinical benefit, whether that be anti-inflammatory or antimicrobial. Although we detected no harm to individual patients given azithromycin, there is a risk of harm at a societal level from widespread use of antimicrobial agents. Azithromycin is classified within the WHO Watch Group of Antibiotics (ie, antibiotics that have higher resistance potential and should be prioritised as key targets of antimicrobial stewardship programmes).28 In light of the new evidence from the RECOVERY trial, the widespread use of macrolides in particular and antibiotics in general in patients with COVID-19 should be questioned.29
Strengths of this trial included that it was randomised, had a large sample size, broad eligibility criteria, and more than 98% of patients were followed up for the primary outcome. The trial also had some limitations. Detailed information on laboratory markers of viral load, inflammatory status, immune response, coexistent bacterial infection, or use of non-macrolide antibiotics was not collected, nor was information on radiological or physiological outcomes. Following random assignment, 17% of patients in the usual care group were given azithromycin or another macrolide antibiotic. Although this randomised trial is open label (ie, participants and local hospital staff are aware of the assigned treatment), the outcomes are unambiguous and were ascertained through linkage to routine health data systems (regardless of treatment allocation).
Three other randomised controlled trials have assessed the efficacy of azithromycin for the treatment of COVID-19 in patients admitted to hospital, all of which additionally treated patients with hydroxychloroquine.17, 18, 19 The COALITION I and COALITION II trials found that for patients with COVID-19 who had been admitted to hospital, treatment with azithromycin and hydroxychloroquine was not associated with any improvement in mortality, duration of hospital stay, or clinical status as assessed using an ordinal outcome scale.17, 18 A small trial in Iran that randomly assigned patients to hydroxychloroquine and lopinavir–ritonavir with or without azithromycin also found no significant difference in mortality or intensive care unit admission, but suggested a reduction in duration of hospital stay.19 The total number of patients in all three previous trials combined was 1223, with 130 deaths. The RECOVERY trial, with 7763 participants and 1723 deaths in this assessment of azithromycin, is well powered to detect modest treatment benefits; however, none were observed.
At the time of writing, 24 trials evaluating the use of macrolides in patients with COVID-19 were registered in the WHO International Clinical Trials Registry Platform, of which three (COALITION I and COALITION II, and Q-PROTECT, a study in patients who had not been admitted to hospital) have published results.17, 18, 30 Of the remaining 21, 16 are studying macrolides in inpatients either alone or in combination with other putative treatments, while five are studying macrolides in patients who had not been admitted to hospital with suspected or confirmed COVID-19.
Although our findings do not address the use of macrolides for the treatment of patients with COVID-19 who had not been admitted to hospital with early, mild disease, the results do show that azithromycin is not an effective treatment for patients admitted to hospital with COVID-19.
Data sharing
The protocol, consent form, statistical analysis plan, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, and other relevant study materials are available online. As described in the protocol, the trial steering committee will facilitate the use of the study data and approval will not be unreasonably withheld. De-identified participant data will be made available to bona fide researchers registered with an appropriate institution within 3 months of publication. However, the steering committee will need to be satisfied that any proposed publication is of high quality, honours the commitments made to the study participants in the consent documentation and ethical approvals, and is compliant with relevant legal and regulatory requirements (eg, relating to data protection and privacy). The steering committee will have the right to review and comment on any draft manuscripts before publication. Data will be made available in line with the policy and procedures described on the Nuffield Department of Population Health website Those wishing to request access should complete the online form and e-mail data.access@ndph.ox.ac.uk.
Acknowledgments
Acknowledgments
Above all, we would like to thank the thousands of patients who participated in this study. We would also like to thank the many doctors, nurses, pharmacists, other allied health professionals, and research administrators at 176 NHS hospital organisations across the UK, supported by staff at the NIHR Clinical Research Network, NHS DigiTrials, Public Health England, UK Department of Health and Social Care, Intensive Care National Audit and Research Centre, Public Health Scotland, National Records Service of Scotland, Secure Anonymised Information Linkage at University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland. The RECOVERY trial is supported by a grant to the University of Oxford from UK Research and Innovation (Medical Research Council) and NIHR (MC_PC_19056) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill & Melinda Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_0002/14) and an NIHR Senior Research Fellowship (NIHR-SRF-2015-08-001). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. AbbVie contributed some supplies of lopinavir–ritonavir for use in this study. Tocilizumab was provided free of charge for this study by Roche Products. REGN-COV2 was provided free of charge for this study by Regeneron. The views expressed in this publication are those of the authors and not necessarily those of the NHS, UK Research and Innovation, the NIHR, or the UK Department of Health and Social Care. The authors have no conflict of interest or financial relationships relevant to the submitted work to disclose. No form of payment was given to anyone to produce the manuscript. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The Nuffield Department of Population Health at the University of Oxford has a staff policy of not accepting honoraria or consultancy fees directly or indirectly from industry.
Contributors
This manuscript was initially drafted by PWH and MJL, further developed by the writing committee, and approved by all members of the trial steering committee. PWH and MJL vouch for the data and analyses, and for the fidelity of this report to the study protocol and data analysis plan. PWH, MM, JKB, LCC, SNF, TJ, KJ, WSL, AMo, KR, EJ, RH, and MJL designed the trial and study protocol. MM, AR, GP-A, CB, BP, DC, AU, AA, ST, BY, RB, SS, DM, RH, the data linkage team at the RECOVERY coordinating centre, and the health records and local clinical centre staff listed in the appendix collected the data. ES, NS, and JRE verified the data and did the statistical analysis. All authors contributed to data interpretation and critical review and revision of the manuscript. PWH and MJL had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Writing Committee (on behalf of the RECOVERY Collaborative Group)
Peter W Horby, Alistair Roddick, Enti Spata, Natalie Staplin, Jonathan R Emberson, Guilherme Pessoa-Amorim, Leon Peto, Mark Campbell, Christopher Brightling, Benjamin Prudon, David Chadwick, Andrew Ustianowski, Abdul Ashish, Stacy Todd, Bryan Yates, Robert Buttery, Stephen Scott, Diego Maseda, J Kenneth Baillie, Maya H Buch, Lucy C Chappell, Jeremy Day, Saul N Faust, Thomas Jaki, Katie Jeffery, Edmund Juszczak, Wei Shen Lim, Alan Montgomery, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Marion Mafham, Richard Haynes, Martin J Landray. PWH, AR, and ES contributed equally, and MM, RH, and MJL contributed equally.
Data Monitoring Committee
Peter Sandercock, Janet Darbyshire, David DeMets, Robert Fowler, David Lalloo, Ian Roberts, Janet Wittes.
Declaration of interests
We declare no competing interests.
Contributor Information
RECOVERY Collaborative Group:
Eugenia Abaleke, Mustafa Abbas, Sadia Abbasi, Alfie Abbott, Ashraf Abdelaziz, Sherif Abdelbadiee, Mohamed Abdelfattah, Basir Abdul, Althaf Abdul Rasheed, Rezan Abdul-Kadir, Abdulfatahi Abdulmumeen, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer UA Abeer Ul Amna, Adebanke Aboaba, Hani Abo-Leyah, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Hyacinth-John Abu, Ahmad Abu-Arafeh, Syed M Abubacker, Akata Abung, Yaa Aceampong, Devikumar Acharya, Janet Acheson, Andres Acosta, Catherine Acton, Jacqueline Adabie-Ankrah, Fiona Adam, Matthew Adam, Huzaifa Adamali, Carol Adams, Kate Adams, Richard Adams, Tim Adams, Malgorzata Adamus, Kirsty Adcock, Aderonke Adebiyi, Ken Adegoke, Vicki Adell, Aldrin Adeni, Sherna Adenwalla, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Joyce Adeyemi, Elizabeth Adeyeye, Gabrielle Adkins, Adnan Adnan, John Aeron-Thomas, Lynn Afari, Debbie Affleck, Carmel Afnan, Deborah Afolabi, Muhammad Afridi, Rachel Agbeko, Chris Agbo, Sunil Aggarwal, Arameh Aghababaie, Judith Agwada-Akeru, Kwame A Agyapong, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Jonathan Ah-Chuen, Mahin Ahmad, Ashar Ahmed, Bilal Ahmed, Forizuddin Ahmed, Iram Ahmed, Irshad Ahmed, Liban Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sara Ahmed, Syed H Ahmed, Roa Ahmed Ali, Sana Ahmer, Dhiraj Ail, Adam Ainsley, Mark Ainsworth, Myriam Aissa, Lucy Aitchson, Lindianne Aitken, Bini Ajay, Abdulakeem Ajibode, Ayesha Ajmi, Muhammad N Akhtar, Nasim Akhtar, Suha Akili, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Umeh Akudo, Asma Al Balushi, Majd Al Dakhola, Narendra Aladangady, Sajid Alam, Abbas Al-Asadi, Kyriaki Alatzoglou, Lorraine Albon, Stephen Alcorn, Aggie Aldana, David Alderdice, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ana Alegria, Alison Alexander, John Alexander, Peter DG Alexander, Julyan Al-Fori, Bahij Al-Hakim, Shams Al-Hity, Ali Ali, Anyat Ali, Fawzia R Ali, Jawad Ali, Mariam Ali, Mohammad Ali, Oudai Ali, Sakina Ali, Syed Ali, Abid Alina, Katrin Alizaedeh, Maithem Al-Jibury, Moutaz Alkhusheh, Alison Allanson, Robert Allcock, Eireann Allen, Jonathan Allen, Kerry Allen, Louise Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Kathryn Allison, Bethan Allman, Lynne Allsop, Christine Almadenboyle, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Warkaq Al-Shamkhani, Bashar Al-Sheklly, Mary Alvarez, Maysaa Alzetani, Susan Amamou, Sakarai Ambalavanan, Sarah-Jayne Ambler, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Amjad Amjad, Victoria Amosun, Khaled Amsha, Atul Anand, Samantha Anandappa, Julie Anderson, Laura Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rory Anderson, Prematie Andreou, Angela Andrews, Jill 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Oluwadamilola Ebigbola, Martin Ebon, Sinan Eccles, Chloe Eddings, Michael Eddleston, Maureen Edgar, Katharine Edgerley, Mary Edmondson, Tracy Edmunds, Alexandra Edwards, Andrea Edwards, Catherine Edwards, Joy Edwards, Kennedy Edwards, Mandy Edwards, Steven Edwards, Jenny Eedle, Dawn Egginton, Sarah Eisen, Ugochukwu Ekeowa, Mohamed Ekoi, Ayomide Ekunola, Kate El Bouzidi, Ashley Elden, Jennifer Elder, Haifa Eldew, Diana Eleanor, Maysoon Elfadil, Eman Elfar, Mayy M Elgamal, Amr Elgohary, Stellios Elia, Jennifer Elias, Tania Elias, Nadia Elkaram, Amin Elkhawad, Andrew V Elkins, Julie Ellam, Nikki Ellard, Laura Nicola Ellerton, Amy Elliott, Fiona Elliott, Kerry Elliott, Valmai Elliott, Annie Ellis, Hayley Ellis, Kaytie Ellis, Tak-Yan Ellis, Yvette Ellis, Rahma Elmahdi, Einas Elmahi, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Sally El-Sayeh, Hana El-Sbahi, Tarek Elsefi, Karim El-Shakankery, Sarah Elyoussfi, Jonathan Emberson, John Emberton, Julian Emmanuel, Ingrid Emmerson, Charis Emmett, Michael Emms, Marieke Emonts, Angila Engden, Katy English, Nicola Entwistle, Hene Enyi, Ruth Erin Jones, Agota Ermenyi, Hanif Esmail, Ajmal Eusuf, Brynach Evans, Chris Evans, Debra Evans, Gail Evans, Gareth Evans, Jennifer Evans, Lynn Evans, Melanie Evans, Mim Evans, Morgan Evans, Ranoromanana Evans, Teriann Evans, Terry J Evans, Caroline Everden, Lynsey Evison, Jacqueline Faccenda, Leila Fahel, Youstina Fahmay, Sara Fairbairn, Andy Fairclough, Louise Fairlie, Anne Fajardo, Euan Falconer, John Fallon, David Faluyi, Qayyum Farah, Novin Fard, Amr Farg, Adam Farmer, Katie Farmer, Toni Farmery, Frances Farnworth, Samantha Farnworth, Faiyaz Farook, Hadia Farooq, Sidrah Farooq, Fiona Farquhar, Aaron Farrell, Barbara Farrell, James Farthing, Syeda Farzana, Rahmatu Fasina, Azam Fatemi, Mina Fatemi, Nibah Fatimah, Saul N Faust, Joe Fawke, Sinmidele Fawohunre, Alex Feben, Federico Fedel, Christopher Fegan, Mae Felongco, Lynsey Felton, Tim Felton, Kate Fenlon, Andrea Fenn, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Lisa Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil Fernandes, Candida Fernandez, Eduardo Fernandez, Sonia Fernandez Lopez, Ahmed Feroz, Pietro Ferranti, Thais Ferrari, Catarina Ferreira-De Almeida, Alexandra Ferrera, Emma Ferriman, Nicholas Fethers, Ben Field, Janet Field, Andra Fielding, Julie Fielding, Sarah Fielding, Asma Fikree, Sarah Ann Filson, Joanne Finch, Laurie Finch, Natalie Fineman, Adam Finn, Joanne Finn, Sofia Fiouni, Jo Fiquet, James Fisher, Neil Fisher, Daniel Fishman, Krystofer Fishwick, Marie Fisk, Jan Flaherty, Michael Flanagan, Charles Flanders, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Lucy Fletcher, Sophie Fletcher, Christopher Flood, Jonathan Flor, Vincent Florence, Sharon Floyd, Adama Fofana, Georgina Fogarty, Linda Folkes, Aiwyne Foo, Andrew Foot, Jayne Foot, Jane Forbes, Kathryn Forcer, Jamie Ford, Jennifer Foreman, Caroline Fornolles, Adam Forrest, Ellie Forsey, Thomas Forshall, Elliot Forster, Julian Forton, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Angela Foulds, Ian Foulds, Folakemi Fowe, Emily Fowler, Robert Fowler, Stephen Fowler, Caroline Fox, Claire Fox, Heather Fox, Jonathan Fox, Lauren Fox, Natalie Fox, Simon Fox, Sarah-Jane Foxton, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Theodora Francis-Bacon, Victoria Francois, Sharon Frayling, Martyn Fredlund, Michael Freeborn, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Eleanor French, Anastasia Fries, Matthew Frise, Renate Fromson, Claire Froneman, John Frost, Victoria Frost, Rachel Frowd, Arun Fryatt, Bridget Fuller, Elizabeth Fuller, Tracy Fuller, Duncan Fullerton, Sarah Funnell, John Furness, Hassina Furreed, Waqas Gaba, Elizabeth Gabbitas, Claire Gabriel, Joshua Gahir, Katarzyna Gajewska-Knapik, Christopher Gale, Hugo Gale, Swetha Gali, Bernadette Gallagher, Edith Gallagher, Jude Gallagher, William Gallagher, Catherine Galloway, Emma Galloway, Jacqui Galloway, James Galloway, Laura Gamble, Liz Gamble, Brian Gammon, Jaikumar Ganapathi, Ramesh Ganapathy, Kaminiben Gandhi, Sarah Gandhi, Usha Ganesh, Abrar Gani, Iris Garcia Deniz, Antoni D Gardener, Danielle Gardiner, Emma Gardiner, Kirsty Gardiner, Siobhan Gardiner, Caroline Gardiner-Hill, Jonathan Gardner, Mark Garfield, Atul Garg, Nathan Garlick, Lucie Garner, Zoe Garner, Rosaline Garr, Mark Garton, Florence Garty, Rachel Gascoyne, Hyeriju Gashau, Aoife Gatenby, Erin Gaughan, Alok Gaurav, Mariana Gavrila, Jane Gaylard, Emma Gaywood, Catherine Geddie, Sarah Gee, Gemma Genato, Neil Gent, Susan Gent, Natalie Geoghegan, Nithin George, Sam George, Tina George, Simon Georges, Domonique Georgiou, Leigh Gerdes, Louise Germain, Helen Gerrish, Abel Getachew, Hisham Ghanayem, Auns Ghazanfar, Anca Gherman, Alison Ghosh, Arjun Ghosh, Justin Ghosh, Sudhamay Ghosh, Sarra Giannopoulou, Malick Gibani, Ben Gibbison, Kerry Gibbons, Bethan Gibson, Henry Gibson, Kimberley Gibson, Kirsty Gibson, Sian Gibson, Cat Gilbert, Jeanette Gilbert, Kayleigh Gilbert, Benjamin Giles, Mandy Gill, Lynne Gill, Paul Gillen, Annelies Gillesen, Deborah Gilliland, Robert Gillott, Jemma Gilmore, Danielle Gilmour, Kate Gilmour, Theodora Giokanini-Royal, Anna Gipson, Joanna Girling, Rhian Gisby, Angelena Gkioni, Effrossyni Gkrania-Klotsas, Amy Gladwell, James Glanville, Susannah Glasgow, Jon Glass, Lynn Glass, Lisa Gledhill, Ana Glennon, John Glover, Kyle Glover, Jan Glover Bengtsson, Chevanthy Gnanalingam, Julie Goddard, Wendy Goddard, Emily Godden, Jo Godden, Emma Godson, Aiky Goh, Sunita Gohil, Rebeca Goiriz, Sriya Gokaraju, Raphael Goldacre, Arthur Goldsmith, Portia Goldsmith, Darren Gomersall, Lucia Gomez, Raquel Gomez-Marcos, Ali Gondal, Jack Goodall, Bob Goodenough, Camelia Goodwin, Elizabeth Goodwin, Jayne Goodwin, Paula Goodyear, Rajiv Gooentilleke, Michelle Goonasekara, Sheila Gooseman, Shameer Gopal, Sally Gordon, Hugh Gorick, Stuart Gormley, Michelle Gorst, Thomas Gorsuch, Rebecca Gosling, Henry Goss, Naomi Gott, Elizabeth Goudie, Susan Gould, Melonie Gouldbourne, Lysander Gourbault, Abha Govind, Sharon Gowans, Girish Gowda, Rohit Gowda, Hannah Gower, Thomas Gower, Diana Grabowska, Clive Graham, Donald Graham, Jonathan Graham, Justin Graham, Sharon Graham, Matthew Graham-Brown, Julia Grahamslaw, Gianluca Grana, Tracyanne Grandison, Louis Grandjean, Alison Grant, David Grant, Matthew Grant, Pauleen Grant, Rhys Gravell, Jenny Graves, Alasdair Gray, Catherine Gray, Emily Gray, Georgina Gray, Glaxy Gray, Jackie Gray, Karen Gray, Sebastian Gray, Alan Grayson, Fiona Greaves, Paul Greaves, Charlotte Green, Christopher Green, Frederick Green, Joel Green, Marie Green, Stacey Green, Diarra Greene, Lawrence Greenfield, Philippa Greenfield, Alan Greenhalgh, Daniel Greenwood, Sandra Greer, James Gregory, Jane Gregory, Katie Gregory, Tamsin Gregory, Jill Greig, Julia Greig, Rebecca Grenfell, Teena Grenier, Susan Grevatt, Glaxy Grey, Andrew Gribbin, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Nicola Griffiths, Oliver Griffiths, Sofia Grigoriadou, Steph Grigsby, Russell Gritton, Evelina Grobovaite, Clarissa Grondin, Rachel Groome, Liliana Grosu, Jenny Grounds, Jayne Groves, Neil Grubb, Julie Grundy, Francesca Guarino, Sharada Gudur, Shivang Gulati, Vikas Gulia, Pumali Gunasekera, Kirun Gunganah, Jessica Gunn, Emma Gunter, Alok Gupta, Atul Gupta, Rajeev Gupta, Richa Gupta, Tarun Gupta, Vineet Gupta, Ankur Gupta-Wright, Sambasivarao Gurram, Ishy Gurung, Shraddha Gurung, Hazel Guth, Ruth Habibi, Pamela Hackney, Christian Hacon, Aiman Haddad, Denise Hadfield, Michalis Hadjiandreou, Anna Haestier, Nauman Hafiz, Rana Hafiz-Ur-Rehman, Samantha Hagan, Jack W Hague, Rosemary Hague, Andrew Haigh, Kate Haigh, Christina Haines, Scott Hainey, Morton Hair, Brigid Hairsine, Juraj Hajnik, Anne Haldeos, Carmel Halevy, William Halford, Alistair Hall, Anthony Hall, Chloe Hall, Claire Hall, Emily Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Toni Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Heather Halls, Maryam Hamdollah-Zadeh, Bilal Hameed, Imran Hamid, Mohamad Hamie, Bethany Hamilton, Fergus Hamilton, Leigh Hamilton, Ruth Hamlin, Eleanor Hamlyn, Shirley Hammersley, Kate Hammerton, Bev Hammond, Leah Hammond, Rachel Hammond-Hall, Fiona Hammonds, Nidal Hammoud, Ibrahim Hamoodi, Karen Hampshire, Jude Hampson, Shi Han Lee, Ozan Hanci, James Hand, Soran Handrean, Georgina Hands, Sheharyar Hanif, Amy Hannington, Merhej Hannun, Aidan Hanrath, Jane Hanson, Kathryn Hanson, Mazhar U Haq, Ala Haqiqi, Monjurul Haque, Zoe Harding, Simon Hardman, Kumar Haresh, Rachel Harford, Beverley Hargadon, Carolyn Hargreaves, James Hargreaves, Alice Harin, Mohammed Haris, Helen Harizaj, Edward Harlock, Paula Harman, Tracy Harman, Mark Harmer, Muhammad A Haroon, Charlie H Harper, Heather Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Sian Harrington, Yasmin Harrington-Davies, Claire Harris, Jade Harris, Julie Harris, Laura Harris, Marie-Clare Harris, Nichola Harris, David Harrison, Laura Harrison, Melanie Harrison, Rowan Harrison, Susie Harrison, Tom Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Hans Hartung, Alice Harvey, Angela Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Neda Hasan, Brigitte Haselden, Mohammed Hashimm, Imranullah Hashmi, Zena Haslam, Abdulhakim Hassan, Adil Hassan, Ali Hassan, Waqar Ul Hassan, Philip Hassell, Alex Hastings, Bethany Hastings, Jonathan Hatton, Jennifer Haugh, May Havinden-Williams, Stefan Havlik, Dan Hawcutt, Liz Hawes, Nicola Hawes, Annie Hawkins, Nancy Hawkins, Daniel Hawley, Edward Haworth, Cathy Hay, Jamal Hayat, Anne Hayes, Melony Hayes, Fiona Hayes, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard Haynes, Rachel Hayre, Patrick Haywood, Tracy Hazelton, Phoebe Hazenberg, Zhengmai He, Elizabeth Headon, Carrie Heal, Brendan Healy, Amy Hearn, Angela Heath, Rowan Heath, Diane Heaton, Kerry Hebbron, Neil Hedger, Katrine Hedges, Cheryl Heeley, Elaine Heeney, Rajdeep Heire, David Helm, Ulla Hemmila, Scott Hemphill, Deborah Hemsley, Alistair Henderson, Jennifer Henderson, Steven Henderson, Joanne Henry, Karol Henry, Lavinia Henry, Margo Henry, David Henshall, Gillian Herdman, Rosaleen Herdmangrant, William Herrington, Emilia Heselden, Peta Heslop, Simon Hester, Emily Hetherington, Joseph Hetherington, Andrew Hetreed, Chamila Hettiarachchi, Gihan Hettiarachchi, Hayley Hewer, John Hewertson, Anna Hewetson, Sue Hewins, Claire Hewitt, Davina Hewitt, Richard Hewitt, Robert S Heyderman, Matthis Heydtmann, Joseph Heys, Jonathan Heywood, Meg Hibbert, Naomi Hickey, Alexander Hicks, Jenny Hicks, Scott R Hicks, Daniel Higbee, Jennifer Higgins, Lucy Higgins, Andrew Higham, Martin Highcock, Judith Highgate, Mondy Hikmat, Amanda Hill, Helen Hill, Joanne Hill, Phoebe Hill, Annette Hilldrith, Catherine Hillman-Cooper, Zoe Hilton, Alice Hindmarsh, Paul Hine, Kim Hinshaw, Clare Hird, Jemma Hives, Benson Ho, David Hobden, Gill Hobden, Maria Hobrok, Simon Hobson, Simon Hodge, Lesley Hodgen, Holly Hodgkins, Sally Hodgkinson, David Hodgson, Helen Hodgson, Luke Hodgson, Sheila Hodgson, Gemma Hodkinson, Kenneth Hodson, Matthew Hogben, Lucy Hogg, Lee Hoggett, Abigail Holborow, Becky Holbrook, Catherine Holbrook, Catherine Holden, Jill Holden, Melinda Holden, Thomas Holder, Hannah Holdsworth, Lisa Holland, Maureen Holland, Nicky Holland, Marie Hollands, Elizabeth Holliday, Nina Holling, Nigel Hollister, Laszlo Hollos, Evelyn Holmes, Megan Holmes, Raphael Holmes, Rebecca Holmes, Kelly Holroyd, Lyndsey Holt, Siobhan Holt, Alexandra Holyome, Marie Home, Kate Hong, Andrew Hood, Clare Hooper, Samantha Hope, Susan Hope, Bridget Hopkins, Peter W Horby, Stephanie Horler, Anil Hormis, Rachel Horn, Nicola Hornby, Sophie Horrocks, Latoya Horsford, Megan Horsford, Valana Horsham, Alex Horsley, Ashley Horsley, Elizabeth Horsley, Sarah Horton, Jane Hosea, Toby Hoskins, Ejaz Hossain, Muhammad S Hossain, Rashed Hossain, Maxine Hough, Sarah Hough, Kathryn Houghton, Rebecca Houlihan, Gordon Houston, Hamish Houston, Eleanor Hoverd, Roseanna Hovvels, Lee How, Laura Howaniec, Laura Howard, Linda Howard, Lucy Howard, Sarah Howard, Richard Howard-Griffin, Serena Howe, Mark Howells, Lyn Howie, Alex Howlett, Sophie Howlett, Josh Hrycaiczuk, Desmond Hsu, Hein Htet, Zaw Htet, Naing Z Htoon, Su Htwe, Ying Hu, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Heather Hudson, Alison Hufton, Conor Huggins, Alistair Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Rachel Hughes, Rhian Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Robert Hull, Amanda Hulme, Peter Hulme, Wendy Hulse, George Hulston, Ryan Hum, Charlotte Humphrey, Alasdair Humphries, Joanne Humphries, David Hunt, Fiona Hunt, Jane Hunt, Kristen Hunt, Luke Hunt, Karl Hunter, Neil Hunter, Elizabeth Hurditch, Cian Hurley, Katrina Hurley, Mohammed A Husain, Syeda Y Husaini, Coralie Huson, Ibraar Hussain, Mohammad Hussain, Muhammad Hussain, Reda Hussain, Sajid Hussain, Samia Hussain, Sanniah Hussain, Yasmin Hussain, Mohammed Hussam El-Din, Rebecca Hussey, Christopher Hutchcroft, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Daniella Hydes, Jamie Hyde-Wyatt, Niamh Hynes, Megan Hyslop, Ahmed Ibrahim, Asil Ibrahim, Kamal Ibrahim, Mohamed Ibrahim, Wadah Ibrahim, Muhammad Idrees, Hina Iftikhar, Chukwuemeka Igwe, Mohammad Ijaz, Amaju Ikomi, Clare Iles, Stamatina Iliodromiti, Lorna Ilves, La'ali Imam-Gutierrez, Christopher Imray, Haider Imtiaz, Jack Ingham, Julie Ingham, Rory Ingham, Tejas Ingle, Anne Ingram, Luke Ingram, Peter Inns, Ken Inweregbu, Andreea A Ionescu, Ana 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Sabrina Jansz, Deepa Japp, Catherine Jardine, Ellie Jarvie, Rosina Jarvis, Patrycja Jastrzebska, Hafsa Javed, Lona Jawaheer, Dinakaran Jayachandran, Deepak Jayaram, Geeshath Jayasekera, Lalith Jayasekera, Saman Jeddi, Mohammad S Jeelani, Katie Jeffery, Rachel Jeffrey, Nathan Jeffreys, Benjamin Jeffs, Debbie Jegede, Taylor Jemima, Ifan Jenkin, Alison Jenkins, David Jenkins, Elinor Jenkins, Sarah Jenkins, Sian Jenkins, Stephen Jenkins, Edward Jenner, David Jennings, Jacqui Jennings, Louise Jennings, Virginia Jennings, Ellen Jerome, Douglas Jerry, Ellen Jessup-Dunton, Jorge A Jesus Silva, Kishan Jethwa, Abi Jeyabalan, Akhilesh Jha, Shaman Jhanji, Khoo Jian, Zhixin Jiao, Ana Jimenez Gil, Jithin Jith, Teishel Joefield, Navraj Johal, Karine Johannessen, Aisyah Johari, Annie John, Anu John, Emma Johns, Margaret Johns, Antoinette Johnson, Gillian Johnson, Kathryn Johnson, Luke Johnson, Mark Johnson, Claire Johnston, Janet Johnston, Susan Johnston, Victoria Johnston, Dawn Johnstone, Ed Johnstone, Janet Johnstone, Manohar Joishy, Adam Jones, Annabel Jones, Bryony Jones, Chrissie E Jones, Carys Jones, Charlotte Jones, Gareth Jones, Geraldine Jones, Jac Jones, James Jones, Julie Jones, June Jones, Kate E Jones, Laura Jones, Laura M Jones, Louise Jones, Mathew Jones, Nicola Jones, Paul Jones, Prudence Jones, Quentin Jones, Samantha Jones, Sophie Jones, Steve Jones, Taya Jones, Tim Jones, Tracey Jones, Ramya Jonnalagadda, Rebecca Jordache, Sara Jorgensen, Sanal Jose, Anna Joseph, Rosane Joseph, Sibet Joseph, Mehul Joshi, Pratichi Joshi, Benz Josiah, Tiffany Joyce, Martin Juan, Edward Jude, Parminder Judge, Jessica Juhl, Sirisha Jujjavarapu, Julie Julie Melville, Edmund Juszczak, Deepthi Jyothish, Kasamu Kabiru Dawa, Mark Kacar, Gail Kakoullis, Azad Kala Bhushan, Richard J Kalayi, Roobala Kaliannan Periyasami, Seika Kalsoom, Elisa Kam, Mohamed Kamara, Ajay Kamath, Prakash Kamath, Siddharth A Kamerkar, Nick Kametas, Musaiwale Kamfose, Amin Kanish, Osei Kankam, Thogulava 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Muhammad U Khalid, Amir Khalil, Asma Khalil, Sijjad Khalil, Ali Khan, Al-Imran Khan, Asad Khan, Burhan Khan, Fatimah Khan, Kausik Khan, Lubna Khan, Malik A Khan, Marria Khan, Mohammad Khan, Mohammed R Khan, Nayeem Khan, Omar Khan, Rahila Khan, Shabana Khan, Shahul Khan, Tasaduksultan Khan, Waseem Khan, Usman F Khatana, Jibran Khatri, Jyoti Khatri, Sagira Khatun, Taslima Khatun, Chuen R Khaw, Htet HE Khin, Kiran Khokhar, Najaf Khota, Chloe Khurana, Shruti Khurana, Faith Kibutu, Andrew Kidd, Michelle Kidd, Joe Kidney, Shane Kidney, Will Kieffer, Caroline Kilby, Eliz Kilich, Jee Whang Kim, Sarah Kimber, Andy King, Barbara King, Jennifer King, Kirsten King, Rachel King, Sam King, Victoria King, Emily King-Oakley, Laura Kingsmore, Fiona Kinney, Jeremy Kirk, Amy Kirkby, Emily Kirkham, Gemma Kirkman, Ursula Kirwan, Toby Kitching, Laura Kitto, Lauren Kittridge, Sarah Klaczek, Susan Kmachia, Christopher Knapp, Lucy Knibbs, Alicia Knight, Fraser Knight, Marian Knight, Sarah Knight, Steven 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MacDonald, Sheila MacFadyen, James G MacFarlane, Jill Macfarlane, Laura Macfarlane, Lisa MacInnes, Jill MacIntyre, Kirsten Mack, Callum Mackay, Euan Mackay, Alexander Mackenzie, Matt Mackenzie, Robert MacKenzie Ross, Ami Mackey, Fiona Mackie, Robert Mackie, Carolyn Mackinlay, Claire Mackintosh, Katherine Mackintosh, Colin MacLeod, Mary J MacLeod, Michael Macmahon, Andrew MacNair, Catherine Macphee, Iain Macpherson, Allan MacRaild, Alannah Madden, Mary Madden, Norman Madeja, Paula Madgwick, Madhavi Madhusudhana, Alpha Madu, Lorraine Madziva, Marion Mafham, Emma Magavern, Negar Maghsoodi, Christopher Magier, Marios Magriplis, Natasha Mahabir, Subramanian Mahadevan-Bava, Anjanie Maharajh, Ajit Mahaveer, Bal Mahay, Hibo Mahdi, Thushika Mahendiran, Siva Mahendran, Sarah Maher, Shameera Maheswaran, Parisa Mahjoob-Afag, Ahmed Mahmood, Farhana Mahmood, Hager Mahmoud, Mian Mahmood, Waheed Mahmood, Ewan Mahony, Luke Mair, James Maitland, Rupert Major, Jaydip Majumdar, Mohammad KH Majumder, Stephen Makin, Marius Malanca, Hannah Malcolm, Neeraj Malhan, Gulshan Malik, Mohammed Maljk, Petrina Mallinder, Louise Mallon, Edward Malone, Gracie Maloney, Madhu Mamman, Irene Man, Marco Mancuso-Marcello, Aritri Mandal, Tracy Manders, Lauren Manderson, Justin Mandeville, Roope Manhas, Carmen Maniero, Bobby Mann, Baranitharan Manoharan, Katherine Mansi, Dina Mansour, Isheunesu T Mapfunde, Predeesh Mappa, Hemant Maraj, Gemma Marayan, Clare Marchand, Neil Marcus, Maria Marecka, Gomathi Margabanthu, Jordi Margalef, Lavinia Margarit, Georgios Margaritopoulos, Mike Margarson, Fernandez M Maria del Rocio, Victor Mariano, Ashleigh Maric, Arran Marriott, Nemonie Marriott, Karen Marsden, Paul Marsden, Tracy Marsden, Robyn Marsh, Adam Marshall, Andrew Marshall, Gail Marshall, Henry Marshall, Jaimie Marshall, Jenna Marshall, Nicola Marshall, Emmeline Martin, Hayley Martin, Hope Martin, Jane Martin, Karen Martin, Laila Martin, Michael Martin, Sarah Martin, Winston Martin, Tim Martindale, Marcus 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Shurmer, Loria Siamia, Seshnag Siddavaram, Nasir Siddique, Sohail Siddique, Nyma Sikondari, Malcolm Sim, Robert Sime, Oliver Simmons, Richard Simms, Angela Simpson, Anna Simpson, Danny Simpson, Georgina Simpson, Kathryn Simpson, Kerry Simpson, Phillip Simpson, Thomas Simpson, Janet Sinclair, Ankita Singh, Claire Singh, Jayaprakash Singh, Jyoti Singh, Manjeet Singh, Nadira Singh, Pankaj Singh, Prabhsimran Singh, Salil Singh, Parag Singhal, Surendra Singham, Bryan Singizi, Manas Sinha, Sharad Sinha, Utkarsh Sinha, Guy Sisson, Karthikadevi Sivakumar, Shanmugasundaram Sivakumar, Darshi Sivakumaran, Sivanthi Sivanadarajah, Nicole Skehan, Robert Skelly, Jill Skelton, Orlagh Skelton, Imogen Skene, Denise Skinner, Tabitha Skinner, Victoria Skinner, Agnieszka Skorko, Iwona Skorupinska, Mariola Skorupinska, Amy Slack, Katie Slack, Heather Slade, Mark Slade, Holly Slater, Lynda Slater, Nicola Slawson, Andrew Sloan, Brendan Sloan, Derek Sloan, Grace Sluga, Ellen Small, Samuel Small, Karen D Smallshaw, Andy Smallwood, Carien Smit, Aileen Smith, Amanda Smith, Amy Smith, Andrew Smith, Catherine Smith, Chris Smith, Christopher Smith, Dominic Smith, Eleanor Smith, Hazel Smith, Helen Smith, Jacky Smith, Jeannette Smith, Jessica Smith, John Smith, Kate Smith, Kerry Smith, Lara Smith, Lesley Smith, Linda Smith, Lisa Smith, Loren Smith, Lucy Smith, Matthew Smith, Mel Smith, Rachel Smith, Rebecca Smith, Richard Smith, Sally Smith, Stacey Smith, Stephanie Smith, Susan Smith, Sue Smolen, Sara Smuts, Jennifer Smyth, Naoise Smyth, Anette Snell, Alfred So, Beng So, Michelle Soan, Toluleyi Sobande, Alberto Sobrino Diaz, Basit Sohail, Bina Sohail, Roy Soiza, Olajumoke Solademi, Babak Soleimani, Amanda Solesbury, Louise Solomon, Subash Somalanka, Chandrashekaraiah Somashekar, Raj Sonia, Shiu-Ching Soo, Jennifer Soren, Vittoria Sorice, Apina Sothinathan, Pragalathan Sothirajah, Carmen Soto, Najwa Soussi, Donna Southam, David Southern, Iain Southern, Louise Southern, Sara M Southin, Thomas Southworth, Jason Sowter, Claudia Spalding, Enti Spata, Katie Spears, Mark Spears, Branwell Spencer, Gisele Spencer, Sue Spencer, Helen Spickett, Jennifer Spillane, William Spiller, Kerry Spinks, Michelle Spinks, Nick Spittle, Johanna Sporrer, Oliver Spring, Gemma Squires, Jack Squires, Rebecca Squires, Ram Sreenivasan, Ramesh Srinivasan, Asha Srirajamadhuveeti, Vino Srirathan, Sybil Stacpoole, Louise Stadon, Jennifer Stahle, Nikki Staines, Roxana Stanciu, Grazyna Stanczuk, Simon Stapley, Natalie Staplin, Michelle Starr, Rachael Stead, Conor Steele, Paula Stefanowska, Alison Stephens, David Stephensen, Courtney Stephenson, Elaine Stephenson, Monique Sterrenburg, Will Stevens, Amy Stevenson, Andrew Stevenson, Daniel Stevenson, Lesley Stevenson, Sarah Stevenson, Claire Stewart, Grant Stewart, Richard Stewart, Jo Stickley, Beverley Stidolph, Gemma Stiller, Sarah Stirrup, Sarah Stock, Alexander Stockdale, Lynne Stockham, Emma Stoddard, Chris Stokes, Ben Stone, Sarah Stone, Sophia Stone, Imogen Storey, Kim Storton, Frederick Stourton, Angela Strachan, Emma Stratton, Jane Stratton, Sam Straw, Dieter Streit, Emma Stride, Sally Stringer, Sophia Strong-Sheldrake, Siske Struik, Carmel Stuart, Anna Stubbs, Harrison Stubbs, Ann Sturdy, Sharon Sturney, Matt Stuttard, Cristina Suarez, Karuna Subba, Chris Subbe, Manjula Subramanian, Vaidyanathan Subramanian, Venkatram Subramanian, Chinari Subudhi, Rebecca Suckling, Srivatsan Sudershan, Taku Sugai, Peter Sugden, Rudresh Sukla, Ali Suliman, Fatimah Suliman, Sugrah Sultan, Alasdair Summers, Samyukta Sundar, Reka Sundhar, Nadia Sunni, Jay Suntharalingam, Amitava Sur, Dharmic Suresh, Shilpa Suresh, Michael Surtees, Danielle Suter, Helen Sutherland, Rebecca Sutherland, Dovile Sutinyte, Deborah Sutton, Sam Sutton, Amy Sutton-Cole, Mihaela Sutu, Marie-Louise Svensson, Sima Svirpliene, Andrew Swain, Thomas Swaine, Keshav Swarnkar, Tirion Swart, Ealish Swift, Pauline Swift, Rachael Swift, Rachel Swingler, Sophie Swinhoe, Katarzyna Swist-Szulik, Luke Swithenbank, Yasir Syed, Catriona Sykes, Daisy Sykes, Dominic Symon, Lesley Symon, Jen Syson, Gemma Szabo, Tamas Szakmany, Megan Szekely, Matthew Szeto, Maria Tadros, Lucy Tague, Hasan Tahir, Abigail Takyi, James Talbot-Ponsonby, Bradley Tallon, Bee TT Tan, Hock Tan, Huey Tan, WeiTeen Tan, Anand Tana, Rebecca Tangney, Christina Tanney, Tabitha Tanqueray, Emma Tanton, Hayley Tarft, Syed Tariq, David Tarpey, Antonia Tasiou, Elizabeth Tatam, Margaret Louise Tate, Paul Tate, Kate Tatham, Vera Tavoukjian, Alexander Taylor, Andrew Taylor, Beverley Taylor, Claire Taylor, David Taylor, Jennifer Taylor, Joanne Taylor, Julie Taylor, Karen Taylor, Leanne Taylor, Margaret Taylor, Matthew Taylor, Melanie Taylor, Natalie Taylor, Rachael Taylor, Rachel Taylor, Samantha Taylor, Suzanne Taylor, Tracey Taylor, Vicky Taylor, Michelle Taylor-Siddons, Thomas Taynton, Amelia Te, Jessica Teasdale, Julie Tebbutt, Caroline Tee, Adam Telfer, Vibha Teli, Jennifer Tempany, Julie Temple, Natalie Temple, Helen Tench, Yi He Teoh, Lynne Terrett, Louise Terry, Louise Terry, Dariusz Tetla, Daniel Tewkesbury, Manish Thakker, Mini Thankachen, Dushen Tharmaratnam, Hilary Thatcher, Andrew Thayanandan, Krishna Thazhatheyil, Eaint Thein, Byron Theron, Phyu Thet, Kapeendran Thevarajah, Brinda Thillainathan, Yvette Thirlwall, Muthu Thirumaran, Alice Thomas, Amy Thomas, Andrew Thomas, Emma Thomas, Enson Thomas, Esther Thomas, Helen Thomas, James Thomas, Karen Thomas, Koshy Thomas, Lucy Thomas, Megan Thomas, Rachel Thomas, Rebecca Thomas, Rhys Thomas, Ruth Thomas, Sarah Thomas, Sherine Thomas, Tessy Thomas, Vicky Thomas, Rhian Thomas-Turner, Catherine Thompson, Christopher Thompson, Clara Thompson, Fiona Thompson, Katharine Thompson, Laura Thompson, Liz Thompson, Orla Thompson, Roger Thompson, Jason Thomson, Nicola Thomson, Natasha Thorn, Charlotte Thorne, Nicola Thorne, Jim Thornton, Richard Thornton, Sarah Thornton, Susan Thornton, Thomas Thornton, Christopher Thorpe, Sarah Thorpe, Paradeep Thozthumparambil, Laura Thrasyvoulou, Hannah Thraves, Guy Thwaites, Simon Tiberi, Serena Tieger, Carey Tierney, Caroline Tierney, Mark Tighe, Sorrell Tilbey, Amanda Tiller, Elizabeth Timlick, Hayley Timms, Anne-Marie Timoroksa, Samakomva Tinashe, Heather Tinkler, Marianne Tinkler, Jacqui Tipper, Sophie Tisi, Helen Tivenan, Suzy Tluk, Helen T-Michael, Anne Todd, Jackie Todd, Stacy Todd, Mohamed Tohfa, Melanie Tolson, Ana L Tomas, Natalia Tomasova, Sharon Tomlin, Simon Tomlins, Ivan Tonna, Kirsty Topham, Mathew Topping, Parisa Torabi, M Estee Torok, Mark Toshner, Ruhaif Tousis, Peter Tovey, Gareth Towersey, Jill Townley, Richard Tozer, Myat T Trafford, Helen Tranter, Christopher Travill, Sarah Traynor, Ascanio Tridente, Sanchia Triggs, Fiona Trim, Alex Trimmings, Tom Trinick, Maria Tripouki, Ashifa Trivedi, Dawn Trodd, Amy Trotter, Madeleine Trowsdale Stannard, Nigel Trudgill, Daniel Trushell-Pottinger, Maria Truslove, Shaun Trussell, Tariq Trussell, Kyriaki Tsakiridou, Christine Tsang, Peter Tsang, Kyriaki K Tsilimpari, Georgios Tsinaslanidis, Simon Tso, Sally Tucker, Aisha Tufail, Redmond Tully, Killian Turbitt, Rezon Turel, Tolga Turgut, Claudia Turley, Alison Turnbull, Aine Turner, Ash Turner, Charlotte Turner, Gail Turner, Kate Turner, Kelly Turner, Lucy Turner, Mark Turner, Patricia Turner, Sally Turner, Samantha Turner, Victoria Turner, Sharon Turney, Jon Turvey, Emma Twohey, Bhavya Tyagi, Vedang Tyagi, Abigail Tyer, Jayne Tyler, Jennifer Tyler, Alison Tyzack, Petros Tzavaras, Mohammad S Uddin, Ruhama Uddin, Waqar Ul Hassan, Salamat Ullah, Sanda Ullah, Athavan Umaipalan, Judith Umeadi, Akudo Umeh, Wilfred Umeojiako, Lizzie Undrell, Adam Unsworth, Veerpal SU Uppal, Gerry Upson, Alison Uriel, Sebastian Urruela, Hiromi Uru, Miranda Usher, Rebecca Usher, Andrew Ustianowski, Linda C Vaccari, Abhay Vaidya, Erika Vainieri, Bernardas Valecka, Jennifer Valentine, Balan Valeria, Luke Vamplew, Ekaterini Vamvakiti, Joannis Vamvakopoulos, Maud van de Venne, Alex van der Meer, Nora van der Stelt, Lynne Van Koutrik, Joseph Vance-Daniel, Rama Vancheeswaran, Samuel I Vandeyoon, Padma Vankayalapati, Chloe Vansomeren, William Van't Hoff, Sejal Vara, Anu Varghese, Maria Varghese, Teena Varghese, William Varney, Giulia Varnier, Valeria Vasadi, Vimal Vasu, Vasanthi Vasudevan, Ramu Vathenen, Manu Vatish, Heloyes Vayalaman, Christopher Vaz, Niki Veale, Bar Velan, Swati Velankar, Luxmi Velauthar, Neyme Veli, Nicola Vella, Anitha Velusamy, Ian Venables, Mavi Venditti, Ramya Venkataramakrishnan, Richard Venn, Robert Venn, Lyn Ventilacion, Mark Veres, Stefania Vergnano, Will Verling, Amit Verma, Britney Vernon, Nathan Vernon, Mark Vertue, Natalie Vethanayagam, Lucy Veys, Jennifer Vidler, Denise Vigni, Vinod W Vijayaraghavan Nalini, Enric Vilar, Neringa Vilimiene, Joseph Villiers, Sylvia Vinay, Latha Vinayakarao, Rachel Vincent, Rosie Vincent, Lisa Vincent Smith, Emma Virgilio, Abdullah M Virk, Elisa Visentin, Karunakaran Vithian, Alain Vuylsteke, Eleftheria Vyras, Richard Wach, Beverley Wadams, Susan Wadd, Natalia Waddington, Kirsten Wadsworth, Syed EI Wafa, Daniel Wagstaff, Lynda Wagstaff, Dalia Wahab, Zaroug Wahbi, Khalilullah Wahdati, Sawan Waidyanatha, Rachel Wake, Alice Wakefield, Emma Wakefield, Harry Wakefield, William Wakeford, Fiona Wakinshaw, Andrew Walden, Lorna Walding, Claire Walker, Ian Walker, Kevin Walker, Kim Walker, Linda Walker, Marie Walker, Rachel Walker, Susan Walker, Elaine Wall, Rebecca Wallbutton, Jessica Wallen, Karl Wallendszus, Arabella Waller, Michael Waller, Rosemary Waller, Gabriel Wallis, Louise Wallis, Donna Walsh, Elizabeth Walsh, Lani Walshaw, Daniel Walter, Holt Walters, Jocelyn Walters, Eileen Walton, Maggie Walton, Michael Walton, Olivia Walton, Susan Walton, Mandy Wan, Thin Wan, Mary Wands, Rachel Wane, Frank Wang, Nick Wang, Ran Wang, Deborah Warbrick, Samantha Warburton, Deborah Ward, Emma Ward, Katie Ward, Luke Ward, Rachael Ward, Thomas Ward, Scott A Warden, Steve Wardle, Hassan Wardy, Tobias Wareham, Scott Waring, Jenny Warmington, Ben Warner, Christian Warner, Lewis Warnock, Sarah Warran, Lisa Warren, Yolanda Warren, Hannah Warren-Miell, Hazel J Watchorn, Holly Waterfall, Abby Waters, Donald Waters, Mark Waterstone, Catherine Watkins, Catrin Watkins, Eleanor Watkins, Karen Watkins, Lynn Watkins, Adam JR Watson, Ekaterina Watson, Eleanor Watson, Paul Watson, Robert Watson, Malcolm Watters, Donna Watterson, Daniel Watts, John Watts, Merlin Watts, Victoria Waugh, Emma Wayman, Akhlaq Wazir, Nick Weatherly, Hayley Webb, Kathryn Webb, Stephen Webb, Ian Webster, Tim Webster, Ling Wee, Thanuja Weerasinghe, Janaka Weeratunga, Maria Weetman, Shuying Wei, Freshtah Weidi, Hugh Welch, James Welch, Leanne Welch, Steven Welch, Samantha Weller, Claire Wells, Susan Wellstead, Berni Welsh, RIchard Welsh, Ingeborg Welters, Rachael Welton, Lauren Wentworth, Kate Wesseldine, Magdelena West, Raha West, Ruth West, Sophie West, Heather Weston, Alice Westwood, Bill Wetherall, Helen Wheeler, Matthew Whelband, Amanda Whileman, Jenny Whitbread, Benjamin White, Catherine White, Christopher White, Duncan White, James White, Jonathan White, Katie White, Marie White, Nick White, Sarah White, Sonia White, Tracey White, Catherine Whitehead, Anne Whitehouse, Claire Whitehouse, Tony Whitehouse, Sophie Whiteley, Gabriel Whitlingum, Elizabeth Whittaker, Lindsay Whittam, Ashley Whittington, Helen Whittle, Eunice Wiafe, Lou Wiblin, John Widdrington, Jason Wieboldt, Hannah Wieringa, Cornelia Wiesender, Laura Wiffen, Andrew Wight, Christopher Wignall, Danielle Wilcock, Emma Wilcock, Louise Wilcox, Karen Wild, Laura Wild, Stephen Wild, Michael Wilde, Peter Wilding, Tracey Wildsmith, Joe Wileman, Joy Wiles, Kate Wiles, Elva Wilhelmsen, Thomas Wiliams, David Wilkin, Hannah Wilkins, Joy Wilkins, Suzanne Wilkins, Iain Wilkinson, Lesley Wilkinson, Nicola Wilkinson, Sophia Wilkinson, Susan Wilkinson, Tim Wilkinson, Sylvia Willetts, Alexandra Williams, Alison Williams, Angharad Williams, Ava Williams, Carl Williams, Caroline V Williams, Claire Williams, Dewi Williams, Felicity Williams, Gail Williams, Hannah Williams, James Williams, Jennie Williams, John Williams, Joseph JR Williams, Karen Williams, Kathryn Williams, Marie Williams, Matthew Williams, Patricia Williams, Penny Williams, Samson Williams, Sarah Williams, Sophie Williams, Tamanna Williams, Annie Williamson, Cath Williamson, Catherine Williamson, Dawn Williamson, James D Williamson, Elizabeth Willis, Emily Willis, Heather Willis, Herika Willis, Joanna Willis, Louise Wills, Lucy Willsher, Francesca Willson, Alison Wilson, Andrea Wilson, Antoinette Wilson, Debbie Wilson, James Wilson, Kate Wilson, Lucinda Wilson, Mark Wilson, Toni Wilson, Tim Wilson, Marlar Win, Tin T Win, Lucinda Winckworth, Laura Winder, Piers Winder, Nicola Window, Simon Winn, Carmen Winpenny, Helen Winslow, Martin Winstanley, Helen Winter, Jonathan Winter, Barbara Winter-Goodwin, Stephen Wisdom, Martin Wiselka, Sophie Wiseman, Steven Wishart, Eric Witele, Nicholas Withers, Janet Wittes, Donna Wixted, Nicola Wolff, Kirsten Wolffsohn, Rebecca Wolf-Roberts, Elena Wolodimeroff, Chi-Hung Wong, Edwin Wong, Jessica SY Wong, Kit Y Wong, Nick Wong, Sam Wong, Caroline Wood, Dianne Wood, Fiona Wood, Hannah Wood, Jennifer Wood, Joe Wood, Lisa Wood, Louise Wood, Michelle Wood, Stephen Wood, Tracy Wood, Katharine Woodall, Rebecca Woodfield, Christopher Woodford, Jill Woodford, Louise Woodhead, Timothy Woodhead, Philip Woodland, Marc Woodman, Jane Woods, Katherine Woods, Sarah Woods, Elizabeth Woodward, Zoe Woodward, Megan Woolcock, Gemma Wooldridge, Rebecca Woolf, Chris Woollard, Louisa Woollen, Emma Woolley, Jade Woolley, Daniel Woosey, Dan Wootton, Joanne Wootton, Stephy Worton, Jonathan Wraight, Lynn Wren, Caroline Wrey Brown, Demi Wright, Francesca Wright, Imogen Wright, Lianne Wright, Rachel Wright, Caroline Wroe, Henry Wu, Peishan Wu, Pensee Wu, Johnathan Wubetu, Retno Wulandari, Kim Wyness, Frederick Wyn-Griffiths, Inez Wynter, Bindhu Xavier, Zhongyang Xia, Masseh Yakubi, May Yan, Michael Yanney, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Mark Yates, Charlotte Yearwood Martin, Khin Yein, Robert Yellon, Fiona Yelnoorkar, Peter Yew, Kawai Yip, Laura Ylquimiche Melly, Inez Ynter, Cissy Yong, Jemma Yorke, Abdel Younes Ibrahim, Gail Young, Louise Young, Sajeda Youssouf, Ahmed Yousuf, Chrissie Yu, Bernard Yung, Daniel Yusef, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Ausra Zdanaviciene, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Xiaobei Zhao, Dongling Zheng, Jane Zhixin, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei T Zin, Vivian Zinyemba, Christos Zipitis, Arkadiusz Zmierczak, Azam Zubir, Naz Zuhra, Rasha Zulaikha, Carol Zullo, and Ana Zuriaga-Alvaro
Supplementary Material
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The protocol, consent form, statistical analysis plan, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, and other relevant study materials are available online. As described in the protocol, the trial steering committee will facilitate the use of the study data and approval will not be unreasonably withheld. De-identified participant data will be made available to bona fide researchers registered with an appropriate institution within 3 months of publication. However, the steering committee will need to be satisfied that any proposed publication is of high quality, honours the commitments made to the study participants in the consent documentation and ethical approvals, and is compliant with relevant legal and regulatory requirements (eg, relating to data protection and privacy). The steering committee will have the right to review and comment on any draft manuscripts before publication. Data will be made available in line with the policy and procedures described on the Nuffield Department of Population Health website Those wishing to request access should complete the online form and e-mail data.access@ndph.ox.ac.uk.