June 20, 2020
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has stopped enrollment in its clinical trial evaluating whether hydroxychloroquine and azithromycin can prevent hospitalization and death from coronavirus disease 2019 (COVID-19). This action was taken because NIAID, the study leadership and the independent data and safety monitoring board (DSMB) overseeing the trial determined that the rate of participant enrollment has been inadequate for the trial to meet its objectives in a timely manner. No safety concerns were associated with the trial.
Launched in May 2020, the NIAID-sponsored Phase 2b trial aimed to determine whether a short course of hydroxychloroquine and azithromycin could safely and effectively prevent disease progression among adults with mild-to-moderate COVID-19. Hydroxychloroquine is approved by the Food and Drug Administration to treat autoimmune diseases and to prevent and treat malaria. Preliminary evidence had suggested that the drug, alone or in combination with the FDA-approved antibiotic azithromycin, might benefit people with COVID-19.
Although recent research suggests that hydroxychloroquine may not be an effective treatment for patients hospitalized with COVID-19, the question of whether it offers benefit when given early in the course of the disease remains unanswered. The NIAID study, conducted by the AIDS Clinical Trials Group (ACTG), sought to fill this knowledge gap by testing it in a randomized, placebo-controlled trial—considered the gold standard for determining whether an intervention can benefit patients.
The study, conducted at ACTG sites across the United States, planned to rapidly enroll approximately 2,000 adults who had laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, and were experiencing symptoms consistent with COVID-19. Participants were randomly assigned to receive either hydroxychloroquine and azithromycin or matching placebo pills to take at home for seven days.
Since its launch in May, however, the study had enrolled only 20 participants, despite efforts by the study sites to enhance recruitment, raising concerns that it would not be feasible to continue the trial to full enrollment. On June 15, FDA revoked an Emergency Use Authorization that had allowed hydroxychloroquine and the related drug chloroquine to be prescribed to hospitalized adolescents and adults with COVID-19. This revocation does not apply to clinical trials and is specific to hospitalized individuals rather than outpatients. However, the decision could further dampen enthusiasm for enrollment in studies evaluating these drugs.
Based on these considerations and in close consultation with the study team, NIAID determined that it is highly unlikely that the ACTG trial, known as A5395, would be able to enroll to completion and meet its intended objectives. The DSMB concurred with this assessment and agreed it would be best to close the trial. Participants, site investigators, institutional review boards and regulators are being notified of this decision. The study team is working with the clinical trial sites to ensure that participants in the trial receive appropriate care.
NIAID remains committed to identifying safe and highly effective treatments for COVID-19. The Institute recently launched a trial evaluating remdesivir plus the anti-inflammatory drug baricitinib for treatment of hospitalized adults with COVID-19. Additional studies, including outpatient studies, are in the planning stages.
For more information about A5395, visit ClinicalTrials.gov and search identifier NCT04358068.