UPMC and University of Pittsburgh School of Medicine physician-scientists—including McGowan Institute for Regenerative Medicine affiliated faculty member Derek Angus, MD, MPH, UPMC chief healthcare innovation officer, chair of the UPP Department of Critical Care Medicine and physician director of the UPMC ICU Service Center, University of Pittsburgh’s inaugural associate vice chancellor for health care innovation, and Distinguished Professor and the Mitchell P. Fink Endowed Chair in Critical Care Medicine at the University of Pittsburgh School of Medicine—contributed to a national study published in the Journal of the American Medical Association (JAMA) reporting findings that “do not support” the use of hydroxychloroquine for the treatment of adult patients hospitalized with COVID-19.
The Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease (ORCHID) study found that, when compared to inactive placebo, hydroxychloroquine did not significantly improve clinical outcomes of patients hospitalized for respiratory illness related to COVID-19.
The study, which was funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, was conducted at 34 hospitals in the Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network, which includes UPMC hospitals.
“Our study—which is supported by the gold-standard in medical research: a blinded, randomized clinical trial—puts to rest any lingering hope that hydroxychloroquine is an effective treatment against COVID-19,” said study co-author Donald Yealy, MD, UPMC’s senior medical director and chair of emergency medicine at Pitt and UPMC. “This allows us to focus our research and funding toward other, more promising treatments while reinforcing the public health tenants of mask-wearing, physical distancing and hand hygiene to prevent the spread of this disease.”
Some laboratory studies suggested hydroxychloroquine can inhibit replication of SARS-CoV-2, the virus that causes COVID-19. Observational studies early in the COVID-19 pandemic suggested that the drug may have beneficial effects for patients with the disease, which sparked great enthusiasm for hydroxychloroquine as a potential treatment.
However, clinical trials, which are considered the highest quality research studies for understanding the effect of a drug in patients, have failed to show beneficial effects of hydroxychloroquine for patients with COVID-19, the researchers said.
“Hydroxychloroquine became a very commonly used medication for COVID-19 in the spring of 2020 without strong evidence that it would be beneficial,” said the study’s lead investigator, Wesley H. Self, MD, MPH, an emergency medicine physician and vice president for Clinical Research Networks and Strategy at Vanderbilt University Medical Center.
“Therefore, we conducted a clinical trial with the strongest methods possible to provide high-quality information on whether hospitalized patients with COVID-19 should be treated with hydroxychloroquine,” Dr. Self said. “Combined with other studies that showed similar findings, we believe this trial provides compelling data for clinicians to stop using hydroxychloroquine for hospitalized adults with COVID-19.”
Between April and June 2020, 479 patients hospitalized for respiratory illness from COVID-19 were enrolled in the ORCHID study, a blinded, placebo-controlled randomized clinical trial.
Patients who were acutely ill and hospitalized with COVID-19 were treated with 10 doses of hydroxychloroquine or placebo over five days. The patient’s clinical status, including hospital discharge, oxygen use, mechanical ventilator use and death, was followed for a month after the medication was started.
The study showed no evidence that hydroxychloroquine prevented death or helped patients recover from COVID-19 more quickly. One month after starting the study, 10.4% of patients treated with hydroxychloroquine and 10.6% of patients treated with placebo had died.
In June, the NHLBI halted the study after determining that hydroxychloroquine was not likely to be of benefit to hospitalized patients with COVID-19.
Additional study author from Pitt and UPMC is Alexandra Weissman, MD, MPH. Other institutions contributing to this research are Intermountain Medical Center, University of Utah, Johns Hopkins University, University of California Los Angeles, Duke University, Massachusetts General Hospital, Wake Forest, University of Colorado, Montefiore Medical Center, Oregon Health and Sciences University, University of Washington, University of California San Francisco, University of Michigan, Harvard University, Beth Israel Deaconess Medical Center and University of Massachusetts.
This research was supported by NHLBI grants 3U01HL123009-06S1, U01HL123009, U01HL122998, U01HL123018, U01HL123023, U01HL123008, U01HL123031, U01HL123004, U01HL123027, U01HL123010, U01HL123033, U01HL122989, U01HL123022 and U01HL123020, as well as National Center for Advancing Translational Sciences grant 5UL1TR002243 and UL1TR001102. Sandoz, a Novartis division, supplied the hydroxychloroquine and placebo used in this trial.
Abstract (Effect of hydroxychloroquine on clinical status at 14 days in hospitalized patients with COVID-19–a randomized clinical trial. Wesley H. Self, MD, MPH; Matthew W. Semler, MD; Lindsay M. Leither, DO; Jonathan D. Casey, MD, MSc; Derek C. Angus, MD, MPH; Roy G. Brower, MD; Steven Y. Chang, MD, PhD; Sean P. Collins, MD; John C. Eppensteiner, MD; Michael R. Filbin, MD; D. Clark Files, MD1; Kevin W. Gibbs, MD; Adit A. Ginde, MD, MPH; Michelle N. Gong, MD, MS; Frank E. Harrell Jr, PhD; Douglas L. Hayden, PhD; Catherine L. Hough, MD, MSc; Nicholas J. Johnson, MD; Akram Khan, MD; Christopher J. Lindsell, PhD; Michael A. Matthay, MD; Marc Moss, MD; Pauline K. Park, MD; Todd W. Rice, MD; Bryce R. H. Robinson, MD, MS; David A. Schoenfeld, PhD; Nathan I. Shapiro, MD, MPH; Jay S. Steingrub, MD; Christine A. Ulysse, MS; Alexandra Weissman, MD, MPH; Donald M. Yealy, MD; B. Taylor Thompson, MD; Samuel M. Brown, MD, MS; for the National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. JAMA, published online November 9, 2020.)