New York clinical trial quietly tests heartburn remedy against coronavirus
By Brendan BorrellApr. 26, 2020 , 12:00 PM
Science’s COVID-19 reporting is supported by the Pulitzer Center.
The fast-growing list of possible treatments for the novel coronavirus includes an unlikely candidate: famotidine, the active compound in the over-the-counter heartburn drug Pepcid. On 7 April, the first COVID-19 patients at Northwell Health in the New York City area began to receive famotidine intravenously, at nine times the heartburn dose. Unlike other drugs the 23-hospital system is testing, including Regeneron’s sarilumab and Gilead Sciences’s remdesivir, Northwell kept the famotidine study under wraps to secure a research stockpile before other hospitals, or even the federal government, started to buy it. “If we talked about this to the wrong people or too soon, the drug supply would be gone,” says Kevin Tracey, a former neurosurgeon in charge of the hospital system’s research.
As of Saturday, 187 COVID-19 patients in critical status, including many on ventilators, have been enrolled in the trial, which aims for a total of 1174 people. Reports from China and molecular modeling results suggest the drug, which seems to bind to a key enzyme in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), could make a difference. But the hype surrounding hydroxychloroquine and chloroquine—the unproven antimalarial drugs touted by President Donald Trump and some physicians and scientists—has made Tracey wary of sparking premature enthusiasm. He is tight-lipped about famotidine’s prospects, at least until interim results from the first 391 patients are in. “If it does work, we’ll know in a few weeks,” he says.
A globe-trotting infectious disease doctor named Michael Callahan was the first to call attention to the drug in the United States. Callahan, who is based at Massachusetts General Hospital and has extensive connections in the biodefense world, has spent time in disease hot zones around the world, including the 2003 outbreak of another coronavirus disease, SARS, in Hong Kong. In mid-January, he was in Nanjing, China, working on an avian flu project. As the COVID-19 epidemic began to explode in Wuhan, he followed his Chinese colleagues to the increasingly desperate city.
The virus was killing as many as one out of five patients older than 80. Patients of all ages with hypertension and chronic obstructive pulmonary disease were faring poorly. Callahan and his Chinese colleagues got curious about why many of the survivors tended to be poor. “Why are these elderly peasants not dying?” he asks.
In reviewing 6212 COVID-19 patient records, the doctors noticed that many survivors had been suffering from chronic heartburn and were on famotidine rather than more-expensive omeprazole (Prilosec), the medicine of choice both in the United States and among wealthier Chinese. Hospitalized COVID-19 patients on famotidine appeared to be dying at a rate of about 14% compared with 27% for those not on the drug, although the analysis was crude and the result was not statistically significant.
…
“If it does work, we’ll know in a few weeks,” says Northwell Health’s Kevin Tracey, who leads the famotidine study. NORTHWELL HEALTH
With both the tantalizing Chinese data and the modeling pointing toward famotidine, a low-cost, generally safe drug, Callahan contacted Tracey about running a double-blind randomized study. COVID-19 patients with decreased kidney function would be excluded because high doses of famotidine can cause heart problems in them.
After getting FDA approval, Northwell used its own funds to launch the effort. Just getting half of the needed famotidine in sterile vials took weeks, because the injectable version is not widely used. On 14 April, the U.S. Biomedical Advanced Research and Development Authority (BARDA), which operates under Kadlec, gave Alchem a $20.7 million contract for the trial, most of which paid Northwell’s costs.
The study’s draft protocol was aimed only at evaluating famotidine’s efficacy, but Trump’s “game-changer” antimalarial drug was rapidly becoming the standard of care for hospitalized COVID-19 patients. That meant investigators would only be able to recruit enough subjects for a trial that tested a combination of famotidine and hydroxychloroquine. Those patients would be compared with a hydroxychloroquine-only arm and a historic control arm made up of hundreds of patients treated earlier in the outbreak. “Is it good science? No,” Tracey says. “It’s the real world.”
Michael Callahan during a medical evacuation of COVID-19 patients from a cruise ship MICHAEL CALLAHAN
…
https://www.sciencemag.org/news/2020/04/new-york-clinical-trial-quietly-tests-heartburn-remedy-against-coronavirus
https://en.wikipedia.org/wiki/Famotidine