Two new clinical trials to test potential treatments foris now ready to launch, the National Institutes of Health said Monday, opening enrollment for the first of a series of federally funded studies aimed at evaluating treatments for long-term symptoms that many COVID-19 survivors still face.
They will begin with a study of the use of Pfizer’s Paxlovid antiviral pills, the NIH announcedwhich is currently only approved by the Food and Drug Administration to treat COVID-19 early in an infection.
Up to 900 patients will be enrolled in the study, which will be named RECOVER-VITAL – a smaller number than previously planned. The trial design has also been adjusted to test taking the pills for 25 days, a difference from another recent Stanford University study that was stopped early. That study had found no evidence that the drug benefited patients, MedPage Today reported earlier this year.
“We were able to get some great feedback from the Food and Drug Administration, as well as others, to really improve the design and make sure we got the answers we needed,” Zimmerman said.
Another part of the trials, titled RECOVER-NEURO, will soon test three approaches aimed at helping problems such as brain fog and memory problems. These include a unit designed to deliver low-level electrical currents into the brain, as well as two web-based “training program” options. Additional trials are set to begin within the next three months.
About 5% of Americans say they continue to do so survey results from the Centers for Disease Control and Prevention.as a result of prolonged COVID, according to
Some of mostincludes extreme fatigue; post-exertional malaise (incapacitating fatigue that worsens after physical or mental activity); brain fog; dizziness; gastrointestinal symptoms; palpitations; chronic cough; chest pain; abnormal movements; and loss of, among other things, smell or taste, which can seriously disrupt patients’ lives for months or years.
“Our hope is that these treatments will work. However, we may learn that some interventions do not provide measurable relief, and this will also inform patient care,” said Dr. Larry Tabak, acting director of the National Institutes of Health, told reporters Monday. .
“A Long Period”
The announcements come months after officials said they hoped to start the trials, which were previously scheduled to begin enrolling in early 2023.
“This trial today, this launch today, is definitely a step in the right direction. It’s a little too late and I wish it was bigger and more comprehensive, but it definitely helps us move the ball forward,” said Washington University clinical epidemiologist Dr. Ziyad Al-Aly.
As head of research at VA St. Louis Healthcare System has Al-Aly led several articles studying the risk factors for prolonged COVID and the toll it can take on patients.
“I wish they had the sense of urgency to get us to this stage two years ago,” he said.
Duke University Medical Center’s Dr. Kanecia Zimmerman, the principal investigator overseeing the studies’ infrastructure, said it had taken time to understand long-term COVID well enough to design the trials and isolate specific measures to determine whether the treatments had succeeded.
The study designs then had to be vetted through a series of governing bodies tasked with overseeing the trials. That process took “a long time,” she said.
After RECOVER-VITAL, the RECOVER-SLEEP research, which will test a range of interventions to improve sleep and wakefulness, is expected to formally launch “within the next few weeks,” she said. The others will launch “in probably two to three months.”
“We’re building the ship as we sail it in some ways. So certainly we’re trying to track those trials, but we know there’s a lot of things that have to happen before trials can start,” Zimmerman said.
NIH officials have for months defended the pace of their research after advocates and Congress questioned how the agency has spent billions that had been earmarked to speed long-standing COVID research.
“The NIH was late to start the clinical trial planning process, and once it started in the fall of 2022, there was so much pressure to get these trials up and running quickly that patient input was often sidelined,” Lauren Stiles, president of the patient advocacy organization Dysautonomia International, told CBS News in an email.
Stiles, who has also served on one of RECOVER’s trial design committees, said she was pleased that the NIH was “finally funding much-needed clinical trials” for long-term COVID. However, she expressed frustration that patient input has been “largely ignored.”
In a announcement, the Long COVID Alliance — an umbrella organization that spans several groups, including Dysautonomia International — praised the “much-needed and long-awaited” launch. But they said “many important questions remain unanswered” about the research.
“Furthermore, the Alliance is concerned that the NIH has not presented a timeline for results: They have highlighted that enrollment will begin over the next several months, which likely means that results to benefit many millions with Long COVID are still at least a year away,” they said.
“The most promising to test”
So far, officials said current plans for the upcoming RECOVER-SLEEP arm will include trials of melatonin, a supplement used to promote sleep, the stimulants modafinil and solriamfetol for patients who struggle to stay awake during day, and “an educational coaching system” to help people improve the quality of their sleep.
Separately, a RECOVER-AUTONOMIC arm will examine treatments for problems in the autonomic nervous system, which controls the body’s involuntary processes. Potential treatments include intravenous immunoglobulin, which is designed to suppress the immune system, and ivabradine, which has been used in chronic heart failure.
Stiles expressed frustration with the two Internet-based “training program” options to be tested in RECOVER-NEURO — one developed by Posit Science Corporation and another by Mount Sinai Health System — as a “huge letdown for patients.”
“The NIH chose to study what is essentially a computer game, not a treatment that actually addresses the underlying biology that causes cognitive impairment,” she said.
Officials said the studies are designed to be an “adaptive platform study” that makes it easy for them to adjust how they test the treatments or add new ones. They said the first tranche of treatments were selected by panels as “the most promising to test.”
“Each of the potential treatments came in with preliminary data and a rationale. And then we had an expert group that formed around each of those platforms,” said NIH’s Dr. Walter Koroshetz.
Al-Aly said the NIH’s announced studies still so far leave out some classes of treatments that have been reported as potentially effective in treating more chronic COVID cases.
A “glaring omission” is the possibility of blood thinners for the so-called “microprop hypothesis,” which suggests that underlying long COVID may be small blood clots that develop in the body’s organs.
“One would hope that there may be more in the future, they are still considering and they may come in the next few months,” he said.