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.