Table 2.
Randomized controlled trials evaluating antimalarials ± azithromycin for the treatment of COVID-19.
| Study | Country | Sample size, population | Antimalarial dosing | Comparator | Primary Outcome | Secondary Outcomes | Main Results |
|---|---|---|---|---|---|---|---|
| Zhaowei Chen et al. | China | 62 hospitalized with pneumonia on chest CT | HCQ 200 mg twice daily for 5 days | Supportive treatment | Time to clinical recoverya - Clinical status |
Radiological demonstration of pulmonary recovery on chest CT | There was a significant difference in time to clinical recovery between the HCQ group (80.6%) and the control (54.8%) (p = 0.05) |
| Huang et al. | China | 22 hospitalized | CQ 500 mg twice daily for 10 days | Antiviral and supportive therapy (Placebo-controlled) | Conversion to negative PCR | - Chest imaging - Length of hospitalization |
There was no significant difference in conversion to negative PCR at 10 days between the CQ group (90%) and the control (75%) (p > 0.05) |
| Lan Chen et al. | China | 48 patients with moderate severity | CQ 1000 mg for one day, then 500 mg daily for nine days OR HCQ 200 mg twice daily for ten days |
Supportive treatment | Clinical recovery | Negative PCR conversion | There was a significant difference in time to clinical recovery between CQ group and the control (CQ shorter, p = 0.019). (HCQ p = 0.049) |
| Tang et al. | China | 150 hospitalized | HCQ 1200 mg for 3 days then 800 mg daily |
Unknown | Conversion to negative PCR of respiratory tract specimens at day 28 | - Negative PCR conversion at 4, 7,10, 14, and 21 days - Clinical status - Laboratory examinations (CRP and lymphocyte count) - Chest imaging |
There was not a significant difference in conversion to negative PCR at 23 days between the HCQ group (70.7%) and the control (74%) (p > 0.05) |
| Jun Chen et al. | China | 30 hospitalized | HCQ 400 mg daily for 5 days | Supportive treatment | Conversion to negative PCR on day 7 - Death within 2 weeks |
- Serious adverse drug event - Clinical status within 2 weeks |
There was not a significant difference in conversion to PCR negativity at 7 days between the HCQ group (86.7%) and the control (93.3%) (p > 0.05) |
| Borba et al. | Brazil | 81 (62 with confirmed COVID-19 infection) | 600 mg HCQ twice daily for 10 days (AZT 500 mg daily for 5 days in ARDS) |
450 mg HCQ twice on day 1 followed by 450 mg daily for 4 days (AZT 500 mg daily for 5 days in ARDS) |
Reduction in mortality by at least 50% | - Mortality on day 13 - Clinical status - Laboratory examinations - ECG on days 13 and 28 - Duration of mechanical ventilation |
There was not a significant difference in mortality at 13 days between the high dose CQ group (39%) and the low dose CQ group (18.9%) (p = 0.03) |
| Horby et al. | UK | 1561 hospitalized | HCQ 1600 mg twice first day, then 400 mg twice daily for 9 days |
Supportive treatment | Mortality at 28 days | - Duration of hospital stay - Intubation |
There was not a significant difference in mortality at 28 days between the HCQ group and the control (RR 1.09, 95% CI 0.96–1.23) |
| Mitja et al. | Spain | 293 non-hospitalized | HCQ 800 mg first day, then 400 mg daily for 6 days |
No treatment | Conversion to negative PCR at 7 days | - Disease progression - Time to symptom resolution |
There was not a significant difference in conversion to negative PCR at 7 days between the HCQ group and the no treatment group |
| Skipper et al. | USA and Canada | 491 non-hospitalized | HCQ 800 mg once, then 600 mg daily for 4 days | Supportive treatment (Placebo-controlled) | Change in symptom severity over 14 days | There was not a significant difference in change in symptom severity at 14 days between the HCQ group and the control (p = 0.21) | |
| Cavalcanti et al. | Brazil | 504 hospitalized | HCQ 400 mg twice daily for 7 days OR HCQ 400 mg twice daily for 7 days + AZT 500 mg daily for 7 days |
Supportive treatment | - Clinical status at 15 days | - Clinical status at 7 days - Intubation - Oxygen requirement - Hospital stay duration - Death |
There was not a significant difference in clinical status at 10 days between the HCQ group and the control (OR 1.21, 95% CI 0.69–2.11; p > 0.05) |
| Boulware. et al. | USA and Canada | 821 asymptomatic participants with exposure to sick contacts with COVID-19 | HCQ 1200 mg twice daily on day 1, then 600 mg daily for 4 days |
Supportive treatment | PCR confirmed COVID-19 or COVID-19-like illness within 14 days | - Hospitalization - Mortality |
There was not a significant difference in COVID-19 with PCR positivity between HCQ group and the control (11.8% vs. 14.3%) (p = 0.35) |
| Mitja et al. | Spain | 2314 asymptomatic participants with exposure to sick contacts with COVID-19 | HCQ 800 mg daily then 400 mg daily for 6 days |
No specific treatment | PCR positivity in 14 days | There was not a significant difference in COVID-19 with PCR positivity between HCQ group and the control (5.7% vs. 6.2%; RR 0.89) (95% CI: 0.54–1.46) |
Abbreviations: HCQ: Hydroxychloroquine; CQ: Chloroquine; AZT: Azithromycin; RR: Relative Risk; OR: Odds Ratio; HR: Hazard Ratio; CI: Confidence Interval; ICU: intensive care unit; PCR: polymerase chain reaction; ARDS: acute respiratory distress syndrome.
a
The definition of clinical recovery in this study is the resolution of fever and cough that is maintained for at least 72 h.