- The National Institutes of Health has stopped two trials of the malaria drug hydroxychloroquine in patients infected with the new coronavirus. One trial was studying patients hospitalized with severe infections, and the other was in people who had symptoms but hadn't yet been admitted to a hospital.
- The oversight board of the trial in hospitalized patients determined hydroxychloroquine wasn't preventing death or the need for more invasive treatment like mechanical ventilation. The trial in non-hospitalized individuals, meanwhile, had enrolled only 20 of a planned 2,000 people, prompting its monitoring board to conclude it couldn't "meet its objectives in a timely manner."
- Hydroxychloroquine gained early attention as a potential COVID-19 treatment because of a few small trials conducted in the early stages of the pandemic, prompting the Food and Drug Administration to grant a since-rescinded authorization for emergency use. Subsequent larger trials comparing the pill to placebo, however, have found no benefit.
Announcement of the trial stops came over the weekend, with the NIH issuing two statements on Saturday. Neither disclosure included safety or effectiveness data.
It's not uncommon for a data monitoring panel to stop a study if the drug being tested isn't showing a benefit, or if patient enrollment is too slow. Rules for halting a trial are drafted before testing begins.
The NIH's decision follows the high-profile halt of a U.K. trial run by the University of Oxford which, like the one of the NIH's studies, was testing hydroxychloroquine in hospitalized patients. Oxford investigators found no evidence of patient benefit.
The NIH study of hydroxychloroquine in hospitalized patients, dubbed ORCHID, began in April when the first patient was treated at Vanderbilt University Medical Center. At the time of the decision to close the trial, 470 of a targeted 500 patients had been enrolled.
ORCHID sought to determine if treatment with hydroxychloroquine kept patients from dying or needing mechanical ventilation, oxygen supplementation or other interventions better than treatment with a placebo.
In an email to BioPharma Dive, the NIH said it plans "expeditious publication" of the ORCHID trial results. Investigators are still following patients to the study’s 15-day endpoint, following which they can conduct the data analysis necessary to submit the trial results for publication, the agency said.
The other study stopped by NIH, known as the A5395 trial, was testing whether hydroxychloroquine, together with the antibiotic azithromycin, could help symptomatic, non-hospitalized patients. Its cancellation blocks one path to obtaining a definitive answer to this question.
The FDA's emergency use authorization, which was issued March 28 and withdrawn on June 15, may have lowered potential participant's incentive to join a clinical trial in which they might have been randomized to receive a placebo instead. The contentious political debate over hydroxychloroquine's potential benefits or harms could have also played a role in the slow enrollment.
Walid Gellad, head of the University of Pittsburgh's Center for Pharmaceutical Policy and Prescribing, called the decision to cancel the trial "a failure of U.S. government response" to the pandemic.
Another trial of hydroxychloroquine in people exposed to SARS-CoV-2 but without symptoms has also shown no benefit. Trials in this post-exposure, pre-symptomatic population being conducted at the University of Washington and Columbia University could shed further light on outpatient use of the drug.
Meanwhile, pre-exposure prevention studies being conducted among health-care workers by Henry Ford Health System and Cambridge University Hospitals in the UK could provide evidence of whether or not hydroxycholoriquine has any use in the pandemic.