Rationale and Design of the COVID-19 Outpatient Prevention Evaluation (COPE - Coalition V) Randomized Clinical Trial: Hydroxychloroquine vs. Placebo in Non-Hospitalized Patients

Abstract

Background: Despite the need for targeting specific therapeutic options for coronavirus disease 2019 (COVID-19), there has been no evidence of effectiveness of any specific treatment for the outpatient clinical setting. There are few randomized studies evaluating hydroxychloroquine (HCQ) in non-hospitalized patients. These studies indicate no benefit from the use of HCQ, but they assessed different primary outcomes and presented important biases for outcome evaluation.

Objective: To evaluate if HCQ may prevent hospitalization due to COVID-19 compared to a matching placebo.

Methods: The COVID-19 Outpatient Prevention Evaluation (COPE) study is a pragmatic, randomized, double-blind, placebo-controlled clinical trial evaluating the use of HCQ (800 mg on day 1 and 400 mg from day 2 to day 7) or matching placebo for the prevention of hospitalization due to COVID-19 in early non-hospitalized confirmed or suspected cases. Inclusion criteria are adults (≥ 18 years) seeking medical care with mild symptoms of COVID-19, with randomization ≤ 7 days after symptom onset, without indication of hospitalization at study screening, and with at least one risk factor for complication (> 65 years; hypertension; diabetes mellitus; asthma; chronic obstructive pulmonary disease or other chronic lung diseases; smoking; immunosuppression; or obesity). All hypothesis tests will be two-sided. A p-value < 0.05 will be considered statistically significant in all analyses. Clinicaltrials.gov: NCT04466540.

Results: Clinical outcomes will be centrally adjudicated by an independent clinical event committee blinded to the assigned treatment groups. The primary efficacy endpoint will be assessed following the intention-to-treat principle.

Conclusion: This study has the potential to reliably answer the scientific question of HCQ use in outpatients with COVID-19. To our knowledge, this is the largest trial evaluating HCQ in non-hospitalized individuals with COVID-19.

Figures

Figura 1. –Diagrama CONSORT mostrando o fluxo de trabalho e o recrutamento planejado para o estudo. ITT: intenção de tratar; mITT: intenção de tratar modificada.

Figura 2. Esquema de coleta de dados e seguimento dos participantes.

Figure 1. CONSORT diagram showing the study workflow and planned recruitment.

Figure 2. Data gathering and participant follow-up scheme.