Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, emerged from a zoonotic source in China in late 2019. Its transmission has been ineffectively controlled and the world has been immersed in a COVID-19 pandemic since early 1st quarter of 2020. While most COVID-19 infections do not require hospitalization, a not insubstantial number of patients develop a respiratory illness that requires hospital care, with a smaller percentage requiring sustained ventilator care. With the growing pandemic, hospitals have been strained beyond capacity and ventilator use has reached near-rationing status. Evidence-based treatments for the disease are needed. This clinical trial sought to add to that evidence base.
In a randomized, controlled, open-label trial of 4,600 patients with COVID-19, hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. Hydroxychloroquine had been proposed as treatment for coronavirus based on in vitro activity SARS-CoV-2 antiviral activity and on data from observational studies reporting effective reduction in viral loads.
In a global trial, 1561 patients were randomized to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality.
The enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P = 0.15). Consistent results were seen in all prespecified subgroups of patients.
The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine.
In their conclusion, the authors note that hydroxychloroquine is not an effective treatment for hospitalized patients with COVID-19.
Source: Effect of hydroxychloroquine in hospitalized patients with COVID-19. The RECOVERY Collaborative Group. N Eng J Med. 2020;383;2030-2040.