Chloroquine and hydroxychloroquine for the treatment of COVID-19: A living systematic review protocol

Abstract

ObjectiveTo determine the relative impact of the use of chloroquine and hydroxychloroquine on outcomes important to patients with COVID 19. DesignThis is the protocol of a living systematic review.We will follow a common protocol for multiple parallel systematic reviews, already published and submitted to PROSPERO (awaiting ID allocation). We will include randomised controlled trials evaluating the effect of chloroquine and hydroxychloroquine -as monotherapy or in combination with other drugs -versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating chloroquine and hydroxychloroquine in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low-or very low-certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

“…We did not review individual trials, nor did we stratify results according to patient characteristics, and we have not collected information on other outcomes than mortality. Such analyses are planned in future publications using in-depth details disclosed in individual trial publications to come [36][37][38] . The exploratory subgroup analyses did not support the hypothesis that blinding/use of placebo is associated with the observed effect (the test for an interaction gives p = 0.15 and the OR is 0.88 with wide CIs 0.55-1.41, compatible with the overall effect); moreover, attrition was negligible (median 0%, IQR 0-0%; range 0-19.5%).…”

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials

“…Such analyses are planned in future publications using in-depth details disclosed in individual trial publications to come. [38][39][40] However, consistent findings in placebo-controlled, double-blinded and open-label trials indicate an overall low risk of bias across trials; moreover, attrition was negligible (median 0%, IQR 0% to 0%; range 0 to19.5%). Meta-epidemiological work shows that mortality results are least affected by lack of blinding, or problems in randomization and allocation concealment as compared with other outcomes.…”

“…Such analyses are planned in future publications using in-depth details disclosed in individual trial publications to come. [44][45][46] The exploratory subgroup analyses did not support the hypothesis that blinding/use of placebo is associated with the observed effect (the test for an interaction gives p=0.15 and the OR is 0.88 with wide CIs [0.55 to 1.41], compatible with the overall effect); moreover, attrition was negligible (median 0%, IQR 0% to 0%; range 0 to 19.5%). A meta-epidemiological study shows little evidence that mortality results would be affected by lack of blinding, or problems in randomization and allocation concealment, in contrast to less objective outcomes.…”

La maladie à coronavirus (COVID-19) : portrait des connaissances actuelles

“…Toutefois, la grande majorité de ces études sont de faible qualité, souvent exemptes de groupes contrôles, et dont la méthode et les résultats n'ont pas été publiés et n'ont pas fait l'objet d'une évaluation scientifique externe [45]. Plusieurs études avec répartition aléatoire présentement en cours visent à évaluer l'efficacité de différents traitements pharmacologiques et permettront certainement d'apporter des données scientifiques claires pour le traitement de la COVID-19 [46]. Inhibiteurs de l'enzyme de conversion de l'angiotensine (IECA) et antagonistes des récepteurs de l'angiotensine (ARA)…”