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More data from observational studies, this time in hospitalized patients, indicated that famotidine (Pepcid AC), which is used to treat heartburn, was associated with improved clinical outcomes in COVID-19 patients.

Use of famotidine in a small group of 83 patients was associated with a lower risk of in-hospital mortality and a combined outcome of death and intubation, reported Jeffrey Mather, MS, of Hartford Hospital in Connecticut, and colleagues.

Moreover, famotidine use was also associated with lower levels of serum markers indicating severe disease, the authors wrote in the .

Famotidine is a histamine-2 receptor antagonist. The authors noted the mechanism by which famotidine might improve COVID-19 outcomes is currently unknown, but hypothesized it might work via "inverse-agonism" of the histamine-2 receptor, which implies SARS-CoV-2 is "at least partially mediated by pathological histamine release," the authors said.

The drug was tied to significant reductions in in-hospital death and a combined death and intubation outcome in hospitalized patients in China, as well as an improvement in symptoms in a small case series of non-hospitalized patients, mostly in the U.S.

Researchers performed a propensity-matched analysis using electronic data from patients testing positive for SARS-CoV-2 from February 24 to May 13 in a single medical center. "Use of famotidine" was defined as either oral or intravenous famotidine, at any dose, within 7 days of COVID-19 screening and/or hospital admission.

Primary outcomes were in-hospital death, requirement for mechanical ventilation, and a composite of death or requirement for ventilation. Secondary outcomes included serum markers of disease severity.

Of 878 total patients, about 10% received famotidine. Mean age of the whole group was 67, and 55% were men. About 22% of patients died during hospitalization, 27% required mechanical ventilation, and 12% met criteria for "combined death and intubation."

About two-thirds of patients receiving famotidine received it only as an inpatient, while 29% took the drug prior to admission and received it as an inpatient. Oral famotidine was administered in the large majority of cases versus intravenous famotidine (83% vs 17%, respectively). Patients who received famotidine tended to be younger, but there were no other significant differences in baseline characteristics or pre-existing comorbidities, the authors noted.

Among the matched study group of 772 patients, 51% received hydroxychloroquine, 51% received azithromycin, 49% received corticosteroids, and about 4% received remdesivir.

Use of famotidine was associated with reduced risk of hospital mortality (OR 0.366, 95% CI 0.155-0.862, P=0.021), as well as a lower risk of the combined death or intubation endpoint (OR 0.495, 95% CI 0.228-0.965, P=0.04).

Intubation occurred in 22% of the famotidine group compared with 32% of the non-famotidine group.

Examining secondary outcomes, use of famotidine was associated with significantly lower median peak C-reactive protein levels and lower median procalcitonin levels. There was also a non-significant trend towards lower median ferritin levels in the famotidine group, the authors noted.

A sensitivity analysis found that the drug seemed to work especially well in patients with the highest national early warning scores (NEWS).

Researchers cautioned that this is a retrospective, observational, single-center study, whose findings should be interpreted with caution. They suggested further research into the effect of famotidine on COVID-19, including dose, route of administration, and timing.

Currently, famotidine is being under an investigational new drug waiver in combination with either hydroxychloroquine or remdesivir.

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