Thomas 2013.
| Methods | A multicentre, randomised, double‐blind, placebo‐controlled trial | |
| Participants | 1. Setting:the trial recruited participants from 28 hospitals in the UK and Ireland, either in hospital setting or retrospectively via medical coding in records or poster adverts
2. Number of participants randomised: 274 3. Sex (men/women):109/165 4. Mean age ± SD: treatment group ‐ 58.1 ± 12.6, placebo group ‐ 57.4 ± 14.4 5. Area of body involved: leg 6. Number of episodes of cellulitis prior to intervention: ≥ 2 |
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| Interventions | Study groups:
Concomitant treatment: "normal clinical practice" for predisposing factors such as tinea pedis Duration of treatment‐ 12 months Follow‐up:on‐prophylaxis phase‐ telephone calls from co‐ordinating centre every 3 months, post‐prophylaxis phase‐ phone calls at 6‐month intervals. In addition participants were asked to complete a study diary and to immediately inform the trial staff on a repeat episode |
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| Outcomes |
Primary outcomes: 1. Time to next episode of cellulitis Secondary outcomes: 1. The proportion of participants with repeat episodes of cellulitis at the end of the treatment phase, and at the end of the non‐intervention follow‐up phase 2. The number of repeat episodes of cellulitis 3. The proportion of participants with new oedema and/or ulceration at the end of the treatment phase, and at the end of the non‐intervention follow‐up phase 4. The number of nights in hospital for the treatment of repeat episodes of cellulitis 5. The number of adverse drug reactions and/or adverse events of interest (death, nausea, diarrhoea, thrush, rash, severe skin reactions, sepsis, and renal failure) 6. Cost effectiveness 7. Predictors of response model to explore the impact of known risk factors in predicting the efficacy of prophylaxis |
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| Notes | 1. Criteria for diagnosis of cellulitis: ‐ Criteria for an episode of cellulitis for study eligibility (index episode):a confirmed diagnosis of cellulitis by the recruiting dermatologist; if the patient was not seen by the recruiting clinician, validation of diagnosis was sought from the medical records and interview with the patient. In this case specific criteria were required consistent with clinical signs and symptoms of cellulitis (specified in the report). Any doubt over the certainty of the diagnosis was grounds for exclusion ‐ Criteria for a repeat episode of cellulitis during treatment or follow‐up phases: next episode of cellulitis in either leg that had been reported by the participant and confirmed by a medical practitioner (sensitivity analysis was performed for patient‐reported cases that required antibiotic treatment and were not confirmed as stated). 2. The paper reported good and balanced adherence in both groups: "A total of 214 participants (78%) reported taking at least 75% of the study tablets; the proportion of patients who reported taking at least 75% of the tablets was similar in the two groups". Funding source and Declaration of interest: NC (Action Medical Research‐ medical research charity) and no conflicts of interests The Thomas 2012 and Thomas 2013 report on 2 studies that were led by the same group of researchers under the title of: Prophylactic Antibiotics for the Treatment of Cellulitis at Home ‐ The PATCH trials (The PATCH II and PATCH I studies, respectively). Similar study designs were reported for both trials including randomisation process, allocation, blinding, definitions of outcomes, monitoring and analysis. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "The coordinating center randomly assigned the participants with the use of the Nottingham Clinical Trials Unit (NCTU) Web‐based randomization service". Comment: Investigators used computer‐generated random list |
| Allocation concealment (selection bias) | Low risk | Quote: "The computer‐generated randomization list was produced before the start of recruitment, with the use of randomly varying block sizes, and was held by the NCTU". Comment: Central block randomisation was conducted with varying block sizes |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "Participants and all members of the study team were unaware of the treatment assignments throughout the trial, and the analysis was performed before the breaking of the randomization code". Comment: The trial included placebo, randomisation list was held by the CTU, breaking of the allocation code was allowed according to decisions by the data monitoring committee and as prespecified in the protocol of the trial |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | As detailed for blinding of the participants and personnel: there was blinding, and it was unlikely that the blinding could have been broken |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "A total of 247 patients (90%) underwent at least 18 months of follow‐up (median, 25)" Comment: attrition was low |
| Selective reporting (reporting bias) | Low risk | All the outcomes prespecified in the protocol were reported and any changes to its plan were explained (see Thomas 2013) |
| Similarity of groups at baseline (baseline imbalance bias) | Low risk | Quote: "The baseline characteristics of the participants were well balanced between the groups". Comment: Baseline characteristics were reported and balanced |
| Early termination (early stopping bias) | Low risk | Sample size calculation was stated (a sample of 260 participants), the goal of recruitment was achieved (274 participants randomised), and the study did not terminate prematurely |
| Other bias | Low risk | No other sources of potential bias were found. |
Abbreviations:
d ‐ Day g ‐ Microgram ITT ‐ Intention‐to‐treat (Table 2) NC ‐ Non‐commercial NF ‐ No follow‐up NR ‐ Not reported SD ‐ Standard deviation