Multiple clinical trials have demonstrated that hydroxychloroquine is ineffective for both preventing and treating COVID-19. These findings contradict earlier hopes that the drug, commonly used for malaria and rheumatic conditions, might offer a solution against SARS-CoV-2.
Prophylactic Use in Healthcare Workers
A randomized, placebo-controlled trial conducted by the University of Minnesota Medical School assessed hydroxychloroquine as a pre-exposure prophylactic for healthcare workers at high risk of COVID-19 exposure. The trial, published in Clinical Infectious Diseases, involved 1,483 participants across the U.S. and Canada who were randomly assigned to receive either once-weekly hydroxychloroquine, twice-weekly hydroxychloroquine, or a placebo. Participants were monitored for a minimum of four weeks, and up to twelve weeks.
The results indicated that hydroxychloroquine did not prevent COVID-19 infection more effectively than the placebo. Specifically, 5.9% of participants in the hydroxychloroquine group developed COVID-19, compared to 7.9% in the placebo group. This difference was not statistically significant. Principal investigator Dr. Radha Rajasingham noted the trial's objective was to rigorously evaluate hydroxychloroquine's potential as a preventative measure in high-risk healthcare workers.
Side effects were reported more frequently in the hydroxychloroquine groups (31% in the once-weekly group and 36% in the twice-weekly group) compared to the placebo group (21%). The most common side effects included nausea, upset stomach, and diarrhea. Importantly, the trial found no increased risk of serious side effects or cardiac complications associated with hydroxychloroquine compared to the placebo.
Treatment of Hospitalized Patients
Further evidence against the use of hydroxychloroquine comes from the National Institutes of Health (NIH) Outcomes Related to COVID-19 treated with Hydroxychloroquine among Inpatients with symptomatic Disease (ORCHID) trial. This trial, which enrolled 479 hospitalized adults with COVID-19 across 34 hospitals in the United States, was halted early when preliminary data suggested no benefit from hydroxychloroquine.
The final data, published in the Journal of the American Medical Association, confirmed that hydroxychloroquine provided no clinical benefit to hospitalized COVID-19 patients. Participants were randomly assigned to receive either hydroxychloroquine or a placebo over five days, and their clinical status was assessed after 14 days using a seven-category scale. The study found similar health status at day 14 between the two groups, with most participants discharged from the hospital and able to perform a range of activities. Mortality rates were also similar, with 25 of 241 patients in the hydroxychloroquine group and 25 of 236 patients in the placebo group dying by day 28.
Dr. Wesley Self, who led the ORCHID trial, emphasized that the lack of effectiveness of hydroxychloroquine was consistent across patient subgroups and for all evaluated outcomes, including clinical status, mortality, organ failures, duration of oxygen use, and hospital length of stay. Dr. James P. Kiley, director of the Division of Lung Diseases at NHLBI, highlighted the importance of the rigorously designed trial in reaching definitive conclusions about hydroxychloroquine's use in COVID-19.
These findings, consistent with other trials conducted in the United Kingdom and Brazil, provide strong evidence against the use of hydroxychloroquine for either preventing or treating COVID-19. Researchers continue to focus on identifying safe and effective therapies for patients suffering from this disease.
