Table 1.
Main studies of HCQ in COVID-19 (retrospective observational studies of > 1000 patients, or randomized controlled trial) regarding efficacy
| Authors/journal/date | Study type | N patients (N HCQ) | Severity | HCQ dosage | Outcome | Toxicity | Comment |
|---|---|---|---|---|---|---|---|
| Bernaola et al. MedRxiv Jul 2020 [21] | Retrosp. multic. (Madrid) | 1645 (1498) | Hospit. | Unspecified | Decrease in mortality before and after propensity matching | Not reported | |
| Million et al.Travel Med Infect Dis May–Jun 2020 [22] | Retrosp. monoc. | 1061 (1061) | Hospit. and “day-care” | 600 mg/day 10 days | 4.6% poor clinical outcome (ICU transfer, death, hosp > 10 days) | 25 mild AE, not serious | + AZM |
| Sbidian et al. MedRxiv Jun 2020 [23] | Retrosp. multic. | 2738 (623) | Hospit. | Unspecified | Discharge rates higher in HCQ group but no difference in mortality after regression analysis | Not reported | |
| Yu et al.Sci Ch Life Sci Aug 2020 [24] | Retrosp. monoc. | 2882 (278) | Hospit. | 400 mg/day 7–10 days | Biological improvement (IL6, troponin), decreased mortality in patient with cardiac injury | Not reported | |
| Catteau et al.Int J Antimicrob Ag Aug 2020 [25] | Retrosp. multic. nationwide | 8075 (4542) | Hospit. | 2400 mg over 5 days | Lower mortality in HCQ group | Not reported | |
| Di Castelnuovo et al. CORIST study Europ J Int Med Aug 2020 [26] | Retrosp. multic. observ. | 3451 (2634) | Hospit. | 400 mg/days 5–15 days | 30% reduction in the risk of death in patient HCQ | Not reported | |
| Arshad et al. Int J of Inf Dis Jun 2020 [27] | Retrosp. multic. observ. | 2541 (1202) | Hospit. | 2800 mg (400 mg ×2 d1, 200 mg ×2 d2–d5) | 13.5% mortality HCQ group vs 26% usual care | No torsade de pointes, but QTc prolonged | |
| Lagier et al.Travel Med Infect Dis Jun 2020 [28] | Retrosp. monoc. | 3737 (3119) | Hospit. and “day-care” | 600 mg/day 10 days | Association decreased risk of ICU transfer, risk of extended hospitalization and risk of death | No torsade de pointes, no sudden death, 25 patients QTc prolongation, 12 discontinuation (3 patients > 500 ms) | + AZM |
| Ayerbe et al.Int and Emerg Medicine Sept 2020 [29] | Retrosp. multic. observ. | 2075 (1857) | Hospit. | 400 mg ×2 d1, 200 mg ×2 d2–d6 | Decreased mortality after adjustment for confounding values | Not reported | |
| Lammers et al.Int J Inf Diseases Sept 2020 [30] | Retrosp. multic. observ. | 1046 (189) | Hospit. | Mean cumulative 1800 mg | No effect on mortality, significant decreased risk of ICU (− 53%) | Not reported | |
| Ip et al.Plos One Aug 2020 [31] | Retrosp. observ. cohort study | 2512 (1914) | Hospit. | Majority 400 mg ×2 d1, 200 mg ×2 d2–d5 | No significant difference in survival between groups | Prolonged QTc leading to discontinuation of HCQ in 4%, arrhythmias leading to discontinuation in 2%, but arrhythmia reported in 5% HCQ vs 4% non HCQ; 1% cardiomyopathy in both groups | |
| Rosenberg et al. JAMA May 2020 [32] | Retrosp. multic. cohort study | 1438 (271) | Hospit. | Unspecified | No significant difference in mortality between groups | 14.4% prolonged QTc vs 5.9% neither drug, 16.2% arrhythmias vs 10.4%, more cardiac arrest in HCQ + AZM (15.5%) and in HCQ group (13.7%) vs 6.8% | |
| Singh et al. Medrxiv May 2020 [33] | Retrosp. multic. cohort study | 3372 (1125) | Hospit. | Unspecified | No significant differences after propensity score matching | Not reported | +AZM in 799 |
| Geleris et al. NEJM Jun 2020 [34] | Retrosp. monoc. observ. | 1376 (811) | Hospit. | 600 mg ×2 d1, 400 mg ×2 d2–d5 | No differences in terms of death and intubation | Not reported | |
| Rivera et al. (CCC19) Cancer DiscJul 20 [35] | Retrosp. multic. observ. cohort study | 2186 (538) | Hospit. | Unspecified | No difference in mortality after multivariable logistic regression; in combination with other drugs, associated with increased mortality | Not reported |
+AZM cancer |
| Mehra et al. LancetMay 2020 [35] | Retrosp. multic. observ. | 90,032 (3016) | Hospit. | Unspecified | Increased mortality (HR 1,335) | Independently associated with increased de novo ventricular arrhythmia during hospitalization | Retracted |
| Horby et al. (RECOVERY) Oct 2020 [36] |
Prosp. RCT blinded |
4716 (1430) | Hospit. | 800 mg h0, 800 mg h + 6, 400 mg h + 12, 400 mg ×2 until d9 | No difference in mortality, worse discharge and ventilation rates for HCQ group; stop enrolment in HCQ arm | 1 case of torsade de pointes, no differences in supraventricular tachycardia frequency, ventricular fibrillation or AV block requiring intervention | |
| Cavalcanti et al. NEJMJul 2020 [37] |
Prosp. RCT open label |
504 (221) | Hospit. | 400 mg ×2 d1–d7 | No effect on mortality, or clinical status at day 15 | 33.7% AE reported in HCQ vs 22% neither group, serious AE in 1% HCQ vs 1.1% in neither group, 14.7% QTc prolonged in HCQ | |
| Hongchao et al. (SOLIDARITY) MedRixvOct 2020 [38] |
Prosp. RCT blinded |
954 (11,266) | Hospit. | 800 mg h0, 800 mg h + 6, 400 mg h + 12, 400 mg ×2 until d10 | No difference in mortality, initiation of ventilation, and duration of stay | Not reported | |
| Self et al. ORCHID JAMA Nov 2020 [39] |
Prosp. RCT blinded |
242 (433) | Hospit. | 400 mg ×2 d1, 200 mg d2–d5 | No difference in survival, or time to discharge, stopped for futility | No significant difference in SAE |
Abbreviation: AZM azithromycin, AV atrioventricular, d day, hospit. hospitalized, ICU intensive care unit, multic. multicentric, monoc. monocentric, observ. observational, prosp. prospective, RCT randomized controlled trial, (S)AE (serious) adverse effect