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Efficacy and safety outcomes in randomized controlled trials investigating hydroxychloroquine for COVID-19
  • Daniela Junqueira,
  • Brian Rowe
Daniela Junqueira
University of Alberta
Author Profile
Brian Rowe
University of Alberta
Author Profile

Abstract

Aims: To assess whether randomized clinical trials (RCTs) proposed to evaluate treatment of COVID-19 with HQ or chloroquine include outcome definitions and data collection plans to produce meaningful efficacy/effectiveness and safety outcomes. Methods: We searched the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) database for registers of RCTs evaluating HQ or chloroquine, alone or in any combination, to treat patients diagnosed with COVID-19 compared with any other treatment option. The final search was performed on April 8th, 2020. Results: Among 51 registered RCTs (median sample size of 262; IQR: 100, 520), 34 (67%) reported a clinical outcome, 12 (24%) a surrogate outcome, and five (10%) a combination of clinical and surrogate outcomes as primary endpoints. Clinical status/recovery and all-cause mortality/mortality accounted for 49% of the unique domains among 20 different clinical outcome domains of efficacy. Twenty-four (47%) RCTs did not describe plans to assess safety outcomes; when assessed, safety outcomes were determined in generic terms of total, severe or serious adverse events. Conclusions: The RCTs investigating HQ or chloroquine include heterogenous and insufficient approaches to measure efficacy/effectiveness and safety that are relevant to patients and clinical practice. These findings provide important insights to inform clinical and regulatory decisions that can be drawn about the efficacy/effectiveness and safety of these agents in patients with COVID-19.

Peer review status:UNDER REVIEW

19 May 2020Submitted to British Journal of Clinical Pharmacology
20 May 2020Submission Checks Completed
20 May 2020Assigned to Editor
23 May 2020Reviewer(s) Assigned
12 Aug 2020Review(s) Completed, Editorial Evaluation Pending
17 Aug 2020Editorial Decision: Revise Minor
14 Sep 20201st Revision Received
15 Sep 2020Submission Checks Completed
15 Sep 2020Assigned to Editor
15 Sep 2020Review(s) Completed, Editorial Evaluation Pending