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Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19

Our take —

While prior in vitro studies suggested hydroxychloroquine has antiviral activity against SARS-CoV-2, this large randomized controlled trial found that the use of hydroxychloroquine in hospitalized patients with COVID-19 does not confer a mortality benefit. Some bias is possible, as 10% of patients did not have confirmed COVID-19 disease, and the study was open-label and not blinded.

Study design

Randomized Controlled Trial

Study population and setting

This study is a subset of the broader Randomized Evaluation of Covid-19 Therapy (RECOVERY) trial, which compares various therapies for the treatment of hospitalized COVID-19 patients. The study described in this article is an open label randomized controlled trial of 4716 hospitalized patients with suspected or confirmed COVID-19 infection across 167 hospitals in the United Kingdom. The study compared the 28-day mortality of patients receiving usual care (n=3155) to patients receiving hydroxychloroquine in addition to usual care (n=1561). Hydroxychloroquine was given via 800 mg loading dose, followed by 400 mg every 12 hours for 9 days or until discharge. In addition to the primary outcome of 28-day mortality, the study measured secondary outcomes including time to discharge, need for invasive mechanical ventilation or extracorporeal membrane oxygenation, or death among patients not receiving invasive mechanical ventilation.

Summary of Main Findings

There was no difference in all-cause mortality at 28 days between patients who received hydroxychloroquine and patients who did not (27.0% in the hydroxychloroquine group vs. 25.0% in the control group; rate ratio 1.09; P=0.15). Of the patients enrolled in the study, 90.5% of them had confirmed COVID-19; in a post hoc analysis of these patients, the rate ratio was the same (1.09). Patients receiving hydroxychloroquine had longer hospital stays on average (16 vs. 13 days). Patients who were given hydroxychloroquine were significantly less likely to be discharged alive within 28 days (59.6% vs. 62.9%; rate ratio=0.90), and significantly more likely to progress to needing invasive ventilation if they did not need it at baseline (risk ratio=1.14; 95CI: 1.03-1.27). Mortality due to COVID-19 was the same between the two groups (24.0% for hydroxychloroquine vs. 23.5% for usual care), but mortality from cardiac causes was slightly higher (by 0.4%) in the hydroxychloroquine group. Rates of various cardiac arrythmias and need for renal dialysis or hemofiltration were comparable between the two groups. There was one case of torsades de pointes as an adverse reaction to hydroxychloroquine.

Study Strengths

The sample size of the study was large, allowing for close matching of participants in the control and intervention arms. 18% of the patients in the study had a Black, Asian, or other minority ethnic background, which is representative of population demographics in the UK.

Limitations

The study is open label and not blinded. As a result, bias is possible. 10% of patients in the trial did not have confirmed COVID-19. While post hoc analysis suggested mortality outcomes in patients with and without confirmed COVID were similar, it is possible the treatment given to these patients may have been affected. Lastly, 6% of recruited patients were not enrolled because of lack of access to hydroxychloroquine at their hospital.

Value added

This well-conducted RCT (part of the RECOVERY trial) provides high quality evidence that the use of hydroxychloroquine does not improve mortality among 4716 hospitalized patients with COVID-19, and is consistent with preliminary findings from the WHO’s SOLIDARITY trial for hydroxychloroquine effectiveness in hospitalized COVID-19 patients.

This review was posted on: 16 November 2020