Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients
Matthieu MILLION, Jean-Christophe LAGIER, Hervé TISSOT-DUPONT, Isabelle RAVAUX, Catherine DHIVER, Christelle TOMEI, Nadim CASSIR, Léa DELORME, Sébastien CORTAREDONA, Sophie AMRANE, Camille AUBRY, Karim BENDAMARDJI, Cyril BERENGER, Barbara DOUDIER, Sophie EDOUARD, Marie HOCQUART, Morgane MAILHE, Coralie PORCHETO, Piseth SENG, Catherine TRIQUET, Stéphanie GENTILE, Elisabeth JOUVE, Audrey GIRAUD-GATINEAU, Herve CHAUDET, Laurence CAMOIN-JAU, Philippe COLSON, Philippe GAUTRET, Pierre-Edouard FOURNIER, Baptiste MAILLE, Jean-Claude DEHARO, Paul HABERT, Jean-Yves GAUBERT, Alexis JACQUIER, Stéphane HONORE, Katell GUILLON-LORVELLEC, Yolande OBADIA, Philippe PAROLA, Philippe BROUQUI, Didier RAOULT
Table 3. Studies evaluating ambulatory treatments to prevent COVID-19 mortalitya.
Study Country Treatment Total sample size Treated Not treated Overall mortality/1000 Odds ratio (95% CI) p-value
95% CI
Studies controlling for age
Mokhtari et al., 2021 [5] Iran HCQ 22,784b 5964b 16,820b 7.0 aOR 0.33 (0.21–0.55) 0.0000082c
Present Study France HCQ+AZ 10,429 1495d 520d 1.5 aOR 0.17 (0.06–0.48) 0.0007
Sulaiman et al., 2020 [6] Saudi Arabia HCQ 5541 1817 3724 11.0 aOR 0.36 (0.16–0.80) 0.012
Ip et al., 2021 [25] USA HCQ 1274 97e 970e 40.0 aOR 0.44 (0.11–1.86) 0.38
Lima-Morales et al., 2021 [26] Mexico IVM+AZ+Montelukast+Acetylsalicylic acid 768 481 287 87.2 aOR 0.19 (0.10–0.36) <0.0001
Reis et al., 2021 (RCT) [27] Brazil HCQ 606 198 408 5.0 Only 3 deaths in untreated 0.30
Studies not controlling for age
Szente Fonseca et al., 2020 [28] Brazil HCQ 717 334 383 15.3 Unadj. OR 0.25 (0.05–1.17) 0.10f
Seftel et al., 2021 [29] USA Fluvoxamine 113 65 48 8.8 Only 1 death in untreated 0.85f
HCQ, hydroxychloroquine; AZ, azithromycin; IVM, ivermectin; RCT; randomized controlled trial; aOR, adjusted Odds ratio; 95% CI, 95% confidence interval.
aOnly community studies are included. Studies in nursing homes are detailed in Supplementary Table 8. bAfter exclusion of 5975 without positive PCR. cCalculated from 95% confidence interval using the formula provided in Altman et al., 2011 [30]. dOnly 2015 patients 60 years are included in the analysis because no death was observed in those younger than 60 years. ePropensity-score-matched patients. fFisher exact test (calculated based on number provided in each article). Excluded studies (no death, absence of systematic PCR diagnosis) are listed in Supplementary Table 9.