Famotidine is a selective histamine H2 receptor antagonist that has been shown to reduce type-I interferon release from SARS-CoV-2-infected epithelial cells.
The small phase II study included 55 non-hospitalised patients with a laboratory-confirmed diagnosis of COVID-19 within the previous 72 hours and a minimum of three symptoms of moderate severity for one to seven days.
Patients were randomised to receive famotidine 80mg three times a day (n=27) or placebo (n=28) for 14 days, with a further 14 days of continued daily monitoring and a final symptom review on day 60.
The time to symptom resolution by day 28 (primary endpoint) was not significantly different between the two study arms (p=0.4), although from day 14 onwards almost twice as many patients in the placebo group remained symptomatic compared with the famotidine group.
However, a comparison of the linear change rate in total symptom score, using data collected from 1,358 patient-submitted longitudinal symptom scores, showed highly significant changing patterns between the two arms, in favour of the famotidine arm (p<0.0001).
The estimated time to 50% symptom resolution was lower for the famotidine group compared with the placebo group (8.2 days versus 11.4 days). Overall, patients in the famotidine group reported earlier resolution for 14 out of 16 assessesd symptoms (87.5%) compared with two out of 16 symptoms for patients in the placebo group (12.5%).
On day 1, most patients had detectable plasma levels of interferon alfa. However, by day 7, significantly fewer patients in the famotidine group had measurable levels (p=0.039). The researchers report that the type I interferon score was correlated with the total symptom score, suggesting that patient-reported symptom severity is linked to sustained interferon-mediated inflammation.
Levels of plasma immunoglobulin type G to the SARS-CoV-2 nucleocapsid core protein were similar in both groups, indicating that famotidine had no effect on adaptive immunity.
Famotidine was shown to be safe and well tolerated with no severe adverse effects observed in either group.
The researchers conclude that their findings show that famotidine is well tolerated and accelerates the resolution of symptoms and inflammation without compromising immunity, thereby supporting its use for COVID-19.
Famotidine is licensed for the treatment of duodenal and benign gastric ulcers, the prevention of relapse of duodenal ulceration, Zollinger-Ellison (Z-E) syndrome and the prevention and treatment of gastro-oesophageal reflux disease. The recommended doses for the licensed indications are lower than those used in the study, with the exception of those for Z-E syndrome.