Table 2.
Characteristics of HCQ therapeutic regimes and their outcomes in key comprehensive clinical studies.
| Investigation/Reference | Investigation Type/Design | Patients (Total No) | Regimes | Severity of COVID-19 Disease | Results/Key Findings | Comment | Location | Limitation | |
|---|---|---|---|---|---|---|---|---|---|
| Con | HCQ | ||||||||
| Chen J et al. (2020) | Randomized and controlled trial | 15 | 15 | HCQ- 400 mg for 5 days | 6–7 days symptomatic patients, unclear severity | Indifferent outcomes in groups. By day 7, no significant change in conversion rate (86.7% vs 93.3%) observed. | Patients were tested negative for COVID-19 at 2 weeks | Shanghai, China | Smaller sample size. Not peer-reviewed, availability in Chinese language |
| Gautret P et al. (2020a) | Open-label trail, Non-randomized, Non-blinded | 16 | 26 | HCQ- 600 mg for 10 days | Asymptomatic patients-17%, Patients with respiratory symptoms- 61%, Chest CT pneumonia +ve patients- 22% | Unadjusted results showed significantly reduced viral titer at day 6 (HCQ-70% vs. con 12.5%, PCR based, p < 0.01) | Exclusion of 6 patients from data (1- died, 1- withdrew, 3 needed ICU admission, 1- lost follow-up) | Marseille, France | Study design, Smaller sample-size, Exclusion of 6 patients, inconclusive long-term outcomes |
| Molina JM et al. (2020) | Prospective open-label investigation | 0 | 10 | HCQ- 600 mg for 5 days + AZM 500 mg × 1, then 250 mg | 10 patients out of 11 were on supplemental oxygen | 8 patients out of 10 were positive at day 5–6 (nasopharyngeal swab) (80%, 95% CI: 49–94) | Patient died-1, Patient transferred to ICU-2, Patient had no further HCQ post prolongation of QTc-1 | Paris, France | Smaller sample size. Not peer-reviewed. |
| Chen Z et al. (2020) | Parallel-group trail Randomized | 31 | 31 | HCQ- 400 mg for 5 days | Mild illness was observed in CT confirmed pneumonia cases | - Clinical recovery and cough remission time reduced in HCQ group, while resolution of pneumonia was higher (80.60% vs. 54.8%) in the HCQ group. | Undefined status, 4 patients developed severe illness in the control group | Wuhan, China | Smaller sample size. Not peer-reviewed. |
| Gautret P et al. (2020b) | Open-label trail, Non-randomized, Non-blinded | 0 | 80 | HCQ- 600 mg for 10 days + 500 mg, followed by 250 mg AZM | Asymptomatic- 5%, Pneumonia cases- 54%, Patients with low national early warning score (NEWS) and mild disease- 92% | Decreased nasopharyngeal viral load at 7th (83% negative) and 8th (93%) days | Patients discharged from hospital - 65 (81.3%), Patients needed ICU admission- 1, Deceased- 1 | Marseille, France | Design of the study, Smaller sample size. Not peer-reviewed. Short follow-up time period |
| Tang W et al. (2020) | Open-label, Multi-centric, Randomized, Controlled trial | 75 | 75 | HCQ- 200 mg for first 3 days, 800 mg for remaining days (total 2–3 weeks) | Patients with mild-moderate disease- 148. Patients with severe illness-2 | HCQ showed no significantly higher negative conversion probability (85.4%) than control (81.3%) patients. Adverse effects were reported in HCQ group | Adverse events in control and HCQ group were reported in 7 and 21 patients respectively | Shanghai, Anhui, Hubei, China | Smaller sample size. Not peer-reviewed. |
| Million M et al. (2020) | Open-label trail, Non-randomized, Non-blinded | 0 | 1061 | HCQ- 200 mg (3 X/day) for 10 days + 500 mg AZM (day-1), followed by 250 mg for next 4 days | Patients had 20.5% and 2.2% moderate and severity scores respectively | In 10 day regime, good clinical results and virological cure were reported in 973 patients (91.7%). HCQ+AZM treatment before COVID-19 illness is safe and has low fatality rate in patients | Majority of patients had relatively mild symptoms at start (95%), therefore, only 10 patients (0.9%) transferred to the ICU, & 8 (0.75%) patients died | Marseille, France | Study design. Incomplete data on some patients. Unsynchronized diagnostic reports |
| Mahevas M et al. (2020) | Multi-centric, Non-Randomized, aim to emulate a target trial | 97 | 84 | HCQ- 600 mg for about ~7–8 days | Most patients had bilateral pneumonia, and 75% moderate or severe illness | No significant relief was observed in HCQ group as compared to control at day 7 in hospitalized patients. All comorbidities were less frequent in the HCQ group. | 17 (20%) patients in the HCQ group, received concomitant AZM, while 64 (76%) received amoxicillin and clavulanic acid. | Créteil, Suresnes, Evry, and Paris, France | Not peer-reviewed. No randomization, Unbalanced prognostic variables across hospitals. |
| Magagnoli J et al. (2020) | Retrospective analysis, Non-randomized | 158 | 97 (HCQ), 113 (HCQ+AZ) | - | All confirmed COVID-19 patients. No severity was specified | No evidence of HCQ either with or without AZM, lessen the risk of mechanical support in patients | Study comprises only men aged over 65 years, most black population | Virginia, and South Carolina, USA |
Study design. Not peer-reviewed. Possibility of selection bias. |
| Mathies D et al. (2020) -Case report | Case report | 0 | 1 | HCQ- 400 mg for 1st day, then 200 mg for remaining 11 days | 77-year-old COVID-19 positive patient with a heart transplant, moderate symptoms | Patient with existing dyspnea and dry cough, showed no further deterioration of the clinical state post HCQ medication. After 12 days, all negative | Patients survived and discharged from hospital after 12 days and had symptoms | Koblenz, Germany | - |
| Lane JCE et al. (2020) -Case series | A multinational, network cohort and self-controlled case series study | 310, 350 (SSZ) | HCQ-956374 HCQ+AZM- 323122, HCQ+ AMX- 351956 | - (variable) | 16 patients had severe adverse events | No excess risk of severe events was identified when 30-day HCQ and SSZ (sulfasalazine) were compare. While, AZM + HCQ increased risk CVD and morality | cardiovascular complications in HCQ+AZM group are likely due to synergistic effects on QT length | Germany, Japan, USA Netherlands, Spain, & UK. | Not peer-reviewed. Potential risk of overlapping in patient datasets, variance in data |
Abbreviations: HCQ, Hydroxychloroquine; CQ, Chloroquine; EC50, Effective Concentration; AZM, Azithromycin; SSZ, Sulfasalazine; AMX, Amoxicillin; CT, Computed tomography; NEWS, National early warning score; PCR, Polymerase chain reaction; ICU, Intensive care unit; QTc, Corrected Q and T wave. ** Last 2 rows in the dark enlist details of clinical case report/series.