Hydroxychloroquine, a well-known drug used for malaria and rheumatologic conditions, has been authorized for emergency use by the FDA to treat COVID-19 at some U.S. hospitals. However, the agency has just released a new cautionary statement about using hydroxychloroquine outside the hospital or clinical trial setting, and preliminary data from a Veterans Administration study found no evidence that use of hydroxychloroquine reduced the risk of mechanical ventilation in patients hospitalized with COVID-19.
Vanderbilt University Medical Center is one site leading a clinical trial to determine if hydroxychloroquine is a safe and effective treatment against the virus.
“Laboratory studies have suggested that hydroxychloroquine may be a useful drug to treat COVID-19,” said lead investigator Wesley Self, M.D., associate professor of emergency medicine at Vanderbilt. “However, high-quality clinical trial data are urgently needed to understand the safety and effectiveness of this drug in COVID-19.”
“High-quality clinical trial data are urgently needed to understand the safety and effectiveness of this drug in COVID-19.”
The ORCHID trial (Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease), will be conducted at multiple locations within the Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network, funded by the National Heart, Lung and Blood Institute. The trial enrolled its first patient on April 2 at Vanderbilt and is anticipated to enroll over 500 patients.
Weighing Benefits and Side Effects
Hydroxychloroquine is an antimicrobial agent with immunomodulatory and antiviral properties that has demonstrated in vitro activity against SARS-CoV-2, the virus that causes COVID-19. Preliminary reports suggest potential efficacy in small human studies.
When used for short periods, hydroxychloroquine is generally well tolerated, Self says, with the most common side effects including nausea, vomiting and diarrhea. However, it can also cause more serious side effects including seizures and cardiac arrhythmia, and it is unknown whether patients acutely ill with COVID-19 are more susceptible to these serious side effects.
While most adults with COVID-19 recover without complications, patients who require hospitalization experience high rates of complications, with up to 31 percent becoming critically ill and requiring ICU admission. The ORCHID trial will help answer whether hydroxychloroquine helps patients recover faster from COVID-19 and, if so, whether the drug’s benefits outweigh its potential side effects.
Isolating Hydroxychloroquine’s Effects
In the blinded, placebo-controlled trial, half of the participants will be treated with hydroxychloroquine, half with a placebo. “This is extremely important so we can isolate the effects of the drug,” Self said.
The intervention group will receive 400 mg of hydroxychloroquine twice daily on the day of enrollment, and then 200 mg twice daily for four subsequent days. The control group is administered a matched placebo twice daily for five days.
Self said the study could be completed within several months, depending on the number of COVID-19 cases at hospitals participating in the trial.
“This study along with other studies planned or ongoing around the world will answer a crucial question. If this drug does not improve outcomes, we need to move on quickly and find treatments that do,” said B. Taylor Thompson, M.D. of Massachusetts General Hospital, which is serving as the coordinating center for the ORCHID trial.
Vanderbilt will also be participating in The Healthcare Worker Exposure Response & Outcomes trial (HERO-HCQ) to research hydroxychloroquine’s effectiveness in preventing COVID-19 in health care workers.