Efficacy and safety outcomes in randomized controlled trials
investigating hydroxychloroquine for COVID-19
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.