Version 1 du 08 Juin 2020
Adjusting series of patients for trial comparisons for COVID-19 treatments
Audrey GIRAUD-GATINEAU, Jean-Christophe LAGIER, Yolande OBADIA, Hervé CHAUDET, Didier RAOULT

Abstract :

Background: SARS-COV-2 has emerged and spread around the world since December 2019. Studies initiated in Marseille by our hospital centre have suggested significant clinical effectiveness of treatment by combining hydroxychloroquine and azithromycin (HCQ+AZ). However, due to the urgency of responding to the pandemic, they were not obtained through randomized controlled trials. Alternative assessment methods are therefore needed.

Methods: We compared our data in silico with those published by two studies comparing other antiviral drugs. For this purpose, random sampling was performed in our cohort to obtain similar groups for disease severity, gender, age and comorbidities associated with chronic diseases with patients included in the remdesivir and lopinavir-ritonavir trials.

Findings: Dual HCQ+AZ therapy was associated with 3 times fewer deaths than similar groups treated either with lopinavir-ritonavir (9% vs 20%, p-value = 0·03) or standard care (8% vs 25·2%, p-value = 0·001). Compared with patients included in the remdesivir study by Wang et al., we also showed a significant difference in the clinical outcome (proportion of cured patients with negative viral load) in favour of HCQ+AZ (77.8% versus 58·2% p = 0·0001).

Interpretation: Although comparison of HCQ+AZ with other antiviral drugs has limitations due to aggregated data, this study provides additional evidence showing that HCQ+AZ should be the systematic treatment of choice after diagnosis of COVID-19-positive cases.

Funding: This work was supported by the French Government under the “Investments for the Future” programme managed by the National Agency for Research (ANR), Méditerranée-Infection 10-IAHU-03, and was also supported by Région Provence Alpes Côte d’Azur and European funding FEDER PRIMMI (Fonds Européen de Développement Régional – Plateformes de Recherche et d’Innovation Mutualisées Méditerranée Infection).

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