Infectious Diseases and Hospital Medicine Act Swiftly to Launch Clinical Trials for Remdesivir
Less than two months after the World Health Organization characterized COVID-19 as a pandemic, the U.S. Food and Drug Administration (FDA) approved emergency use of remdesivir for the treatment of the virulent disease. Later, the FDA gave full approval to remdesivir, which remains the standard of care for hospitalized patients with COVID-19.
Clinical trials, which took place at Stanford and dozens of other sites, yielded convincing data that led to the FDA’s emergency use authorization.
Department of Medicine researchers began recruiting participants for the trials in early March 2020. One pair of trials was sponsored by Gilead Sciences, a company based in Foster City, California, that makes the drug. The other was by the National Institutes of Health (NIH) and one of its institutes, the National Institute of Allergy and Infectious Diseases (NIAID).
The Gilead Trials
Aruna Subramanian, MD, clinical professor of infectious diseases, was the principal investigator of the Gilead trials at Stanford. Subramanian was joined by co-principal investigator Philip Grant, MD, assistant professor of infectious diseases, who helped enroll 46 participants at Stanford and execute these studies. Results were published in the New England Journal of Medicine and the Journal of the American Medical Association.
In results reported April 29, Gilead announced that a five-day treatment course with remdesivir was potentially as effective as 10 days of treatment in its trial of severely ill patients. Later that same day, the NIH reported that early data from its remdesivir trial indicated that the drug helps to accelerate the time to recovery in severely ill patients.
On June 1, results from the remdesivir trial for people with moderate disease stated that a five-day treatment course of remdesivir resulted in a significant clinical improvement over standard of care.
Subramanian says the results from both trials were reassuring to her, both as a scientist and as a doctor who treats patients in the hospital with COVID-19.
“To at least have something that we can potentially use as a treatment for this virus was very assuring,” she says. “In the early course of the pandemic, we were all so scared and disheartened by patients going downhill and needing to be on a ventilator for so long. To see that even those people could potentially be turned around was very encouraging.”
“To at least have something that we can potentially use as a treatment for this virus was very assuring”
The NIH Trial
The process of setting up an infrastructure for clinical trials, slow-moving and deeply complicated under normal circumstances, was accelerated with the outbreak of COVID-19. A team of researchers needs to be assembled, patients need to be recruited, and sites need to be established.
But in a matter of weeks, the division of hospital medicine organized an infrastructure at both Stanford Hospital and Stanford Health Care – ValleyCare and implemented Phase 1 of their first trial—to explore the effectiveness of remdesivir—with impressive results.
Neera Ahuja, MD, chief of the division of hospital medicine, was the principal investigator for the global NIH/NIAID Adaptive COVID-19 Treatment Trial (ACTT) at Stanford. The work was greatly facilitated by Kari Nadeau, MD, PhD, the Naddisy Foundation Endowed Professor of Medicine and Pediatrics and hospital medicine’s senior director of clinical research.
Stanford Hospital and SHC – ValleyCare were among the more than 65 sites around the world hosting the ACTT, a randomized, double-blind, placebo-controlled study that included 1,063 patients for its first phase.
Ahuja and Nadeau worked with clinical associate professor Nidhi Rohatgi, MD, MS; associate professor Sharon Chinthrajah, MD; and clinical assistant professor Rita Pandya, MD, to enroll patients quickly at the Stanford Hospital location. At the other location, David Svec, MD, MBA, clinical associate professor of medicine and chief medical officer at SHC – ValleyCare, was instrumental to the process, along with Minjoung Go, MD, clinical assistant professor of medicine, and Evelyn Ling, MD, MS, clinical assistant professor of medicine and SHC – ValleyCare physician research co-champion.
From left: Evelyn Ling, MD, MS; David Svec, MD, MBA; Minjoung Go, MD
The intense time frame put a great deal of pressure on everyone at Stanford Hospital and SHC – ValleyCare, from the physicians to the staff to the lab workers. When the first trial began, there was no real infrastructure for clinical trials.
As physician research champions, both Go and Ling were leaders on the ground at SHC – ValleyCare, although this was the first clinical trial that either of them had taken such a large part in.
“I was on the night shift, so trying to attend all the daily meetings was a little bit challenging,” Go admits. “It felt a little like trying to fly a plane while you’re building it. But it was a really, really rewarding experience. I got to learn a lot of the process of clinical trials and how to operationalize them.”
That study’s trials showed that recovery time for patients infected with COVID-19 was reduced from 15 days to 11 days with the use of intravenous (IV) remdesivir.
“Data shows remdesivir has a clear-cut positive effect in diminishing the time to recovery,” said Anthony Fauci, MD, director of the NIAID, in a televised meeting at the White House on April 29, the day the results were announced. “What this has proven is that a drug can block this virus,” he said.
“This trial represents the fusion of the Stanford mission, bringing the kind of research that’s typically only at academic centers to a community center, but still being able to use our local nurses, pharmacists, and lab"
“I was very excited by the trial results,” says Ahuja. “Still, this is not a panacea. We don’t know if this is the best treatment. We still need to look for the most effective drug. Here we are in May 2021, a year later. We have the benefit of vaccines, but we still do not have the ideal combination of treatments to rapidly abate the virus.”
Ling says that “this trial represents the fusion of the Stanford mission, bringing the kind of research that’s typically only at academic centers to a community center, but still being able to use our local nurses, pharmacists, and lab. It was a really meaningful first trial. ”