Faced with a global pandemic of a virus previously unknown to humans, the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health has launched a clinical trial to understand if hydroxychloroquine, a well-known drug used for malaria and rheumatologic conditions, is safe and effective in treating hospitalized adults with COVID-19.

The ORCHID trial (Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease), led by Vanderbilt University Medical Center (VUMC), enrolled its first patient on April 2 and will include hundreds of patients to determine if hydroxychloroquine is an effective treatment against the virus projected to hospitalize thousands of U.S. residents in the coming weeks.

The trial is being conducted within the Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network, which is a network of approximately 50 medical centers in the U.S. that collaborate to run large research studies. The PETAL Network is funded by NHLBI.

"Laboratory studies have suggested that hydroxychloroquine may be a useful drug to treat COVID-19," said ORCHID trial lead investigator Wesley H. Self, MD, MPH, an emergency physician at VUMC. "However, we have limited human data to understand if hydroxychloroquine helps patients recover from COVID-19. High-quality clinical trial data are urgently needed to understand the safety and effectiveness of this drug in COVID-19."

While most adults with COVID-19 recover without complications, patients who require hospitalization experience high rates of complications, with up to 26% becoming critically ill and requiring ICU admission.

Despite limited clinical data, hydroxychloroquine has been adopted into treatment guidelines at some hospitals in China and the U.S. because there are no proven medications to help prevent patients from getting worse.

The ORCHID trial is designed to answer the question of whether giving hydroxychloroquine to these patients in the hospital with COVID-19 helps them recover faster without complications, like lung failure requiring assisted breathing with a ventilator.

When used for short periods, hydroxychloroquine is generally well-tolerated, with the most common side effects including nausea, vomiting and diarrhea. However, it can also cause more serious side effects including seizures and a heart conditions (cardiac arrhythmia), which can cause sudden death. It is unknown whether patients acutely ill with COVID-19 are more susceptible to these serious side effects. The ORCHID trial will help answer whether hydroxychloroquine helps patients recover from COVID-19, and if so, whether those benefits outweigh the potential side effects of the drug.

Self said the study could be completed within several months, depending on the number of COVID-19 cases at hospitals participating in the trial. The intervention group in the trial is receiving 400 mg of hydroxychloroquine twice daily for two doses, and then 200 mg twice daily for the subsequent eight doses. The control group is administered matched placebo twice daily for 5 days.

"This is a blinded, placebo-controlled trial, meaning patients, clinicians and the study investigators do not know which patients are receiving the active drug and which are receiving placebo," Self said. "This is extremely important so we can isolate the effects of the drug."

"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 of Massachusetts General Hospital, which is serving as the coordinating center for the ORCHID trial.