Relevent papers
| Author, date, country | Patient group | Study type | Outcomes measured | Results found | Study weaknesses |
| Mahevas et al, 2020, France1 | Adult patients from four French hospitals with confirmed COVID-19 pneumonia infection and requiring at least 2 L/min of oxygen. 181 patients recruited: 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). HCQ was used at a dose of 600 mg/day. | Multicentre, observational data collection | Transfer to ICU within 7 days of inclusion. Death from any cause. Occurrence of ARDS as secondary outcome. | HCQ (raw 19%, weighted proportion 20.5% to non-HCQ (21.6% and 2.1%, respectively). RR 0.93 (95% CI 0.48 to 1.81). HCQ (3.6% and 2.8%) to non-HCQ (4.1% and 4.6%). RR 0.61 (95% CI 0.13 to 2.90). HCQ (28.6% and 27.7%) to non-HCQ (24.2% and 24.1%). RR 1.15 (95% CI 0.66 to 2.01). Eight patients (9.5%) developed long QTs on their ECG requiring HCQ discontinuation. | Examined hospital admissions during a short period only (end of March 2020). Treatment not randomly assigned to groups. Some patients in the HCQ group received concomitant antibiotics. |
| Wei Tang et al, 2020, China2 | 150 patients with laboratory confirmed COVID-19 infection. 75 were assigned to HCQ plus stand-alone care group and 75 to stand-alone care group only. 148 patients deemed moderate/mild disease and only 2 with severe disease. A loading dose of HCQ was given followed by a maintenance dose. | Multicentre, open-label randomised clinical trial | Negative conversion by 28 days. Adverse events. | Negative seroconversion probability in HCQ/SOC group was 85.4% (95% CI 73.8 to 93.8) and 81.3% (95% CI 71.2 to 89.6). The difference between the groups was 4.1% (95% CI 10.3 to 18.5). Diarrhoea 10%. One patient had HCQ discontinued and readjusted in lower dose due to blurred vision. | Underpowered open-label trial. Only included mild and moderately ill patients. 60% patients received concomitant medication before randomisation. Clinically not relevant outcome. HCQ administered late in course of illness. |
| Mingxing et al, 2020, China3 | 22 patients with laboratory confirmed COVID-19. The intervention was HCQ (500 mg two times daily) with 10 patients and the control was lopinavir/ritonavir with 12. | Single-centre open-label randomised clinical trial | Negative swab at 14 days. CT thorax—lung improvement. Discharge at 14 days. Adverse event rate. | RR 1.09 (95% CI 1.00 to 1.33). RR 1.33 (95% CI 1.00 to 2.00). RR 2.00 (95% CI1.33 to 4.00). 90% in the HCQ group. | Unblinded. Very small sample size. |
| Barba et al, 2020, Brazil4 | 81 suspected patients with COVID-19 were randomised to high-dose (HD) or low-dose (LD) HCQ. Either 600 mg two times daily for 10 days or 450 mg once daily for 4 days. | Phase 2 RCT | Lethality. Prolonged QTc | 39% HD (16 of 41) versus 15% LD (6 of 40). OR 3.6 (95% CI 1.2 to 10.6). HD 7 of 37 (18.9%) versus LD 4 of 36 (11.1%). | Double blinded. The trial was interrupted due to safety concerns and all patients were unmasked and reverted to the low dose arm. |
| Gautret et al, 2020, France5 | 80 patients with mild confirmed COVID-19. Dose was 200 mg HCQ three times daily for 10 days with azithromycin. | Single-centre, single-arm interventional study |
| 18.8%. 83% negative at day 7. Median length of stay 4.6 days. | No control arm to compare results, without this context the results are difficult to interpret. Negative nasopharyngeal swabs as an outcome is confounded by disease progression to LRTI or poor technique. |
| Gautret et al, 2020, France6 | 42 patients were enrolled. One hospital gave the intervention of HCQ to patients (n=26), while the other continued normal care (n=10). | Two-centre, non-randomised intervention trial | Negative nasopharyngeal swab. PCR negative. | At day 6, post-enrolment 70% (HCQ) versus 12.5% (control), p=0.001. | This is a non-patient-centred outcome. The treatment the control arm received is not reported. Decreasing titres of virus from the swabs may be affected by technique and disease progression rather than resolution. 3/6 HCQ patients lost to follow-up were not included in the analysis because they were transferred to ICU. One patient was excluded from analysis due to fatality and another due to an adverse reaction to treatment. 6/26 HCQ patients received azithromycin at the treating clinician’s decision. Patients in the control arm were only tested every other day and presumed positive on days not tested. |
| Katheron et al, 2020, Canada7 | This is a reanalysis of the study done by Gautret et al. Using published data, an intention-to-treat analysis was conducted. This included patients that the original authors excluded as lost to follow-up. Reallocated outcomes included one death, three transfers to ITU and an adverse effect to treatment. | The original study is a non-randomised intervention trial | Negative nasopharyngeal swab. PCR negative. | No statistically significant difference in virological clearance rates between the control and HCQ group. | This is a reanalysis based on an original article. |
| Huang et al, 2020, China8 | Enrolled adult patients with confirmed COVID-19 infection in 12 different hospitals. 197 patients allocated to LD (500 mg once daily) or HD (500 mg two times daily) chloroquine phosphate. 176 patients not receiving HCQ used as control. Excluded critical care patients. | Multicentre prospective observational study | Time to undetectable RNA. Proportion of patients with undetectable RNA at day 14. Length of hospital stay. Cessation of fever. Adverse events. | Median number of days IQR 3.0 versus 9.0 difference −6.0 (95% CI −6.0 to − 4.0) with p<0.0001. 57.4% vs 79.6% with p<0.0001. 19 vs 20 days, difference −1 (95% CI −3 to 0.00) with p=0.25. Geometric mean ratio 0.6 (95% CI 0.5 to 0.8) with p=0.0029. 26.9% vs 32.4%. Fewer adverse events were observed in patients with half dose of chloroquine than full dose (absolute difference in proportions −40, 95% CI −60 to −29). | Not a patient-centred outcome. Included mostly mild and moderate cases. |
| Horby and Landray, 2020, UK9 | Ongoing prospective RCT, enrolling adult patients with confirmed COVID-19. 10 infections in 175 hospitals in the UK. 1542 patients recruited to HCQ treatment. 3132 patients randomised to standard care alone. | Multicentre prospective RCT | 28-day mortality. Hospital stay duration. | No significant difference in mortality 25.7% vs 23.5% with p=0.10. HR 1.11 (95% CI 0.98 to 1.26). No evidence of benefit (no further detail available). | Interim analysis. Full trial still ongoing. Results not fully published for critical appraisal yet. |
ARDS, acute respiratory distress syndrome; HCQ, hydroxychloroquine; ICU, intensive care unit; RCT, randomised controlled trial.