Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial
Christina Brennan, Sandeep Nadella, Xiang Zhao, Richard Dima, Nicole Jordan–Martin, Breanna R. Demestichas, Sam O. Kleeman, Miriam Ferrer, Eva Gablenz, Nicholas Mourikis, Michael E Rubin, Harsha Adnani, Hassal Lee, Taehoon Ha, Soma Prum, Cheryl B. Schleicher, Sharon S. Fox, Michael Ryan, Christina Pili, Gary L. Goldberg, James M. Crawford, Sara Goodwin, Xiaoyue Zhang, Jonathan Preall, Ana S.H. Costa, Joseph Conigliaro, Joseph Masci, Jie Yang, David A. Tuveson, Kevin J. Tracey, Tobias Janowitz
Abstract
OBJECTIVE: We assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19. DESIGN: Randomised, double-blind, placebo-controlled, fully remote, phase 2 clinical trial (NCT04724720) enrolling symptomatic unvaccinated adult outpatients with confirmed COVID-19 between January 2021 and April 2021 from two US centres. Patients self-administered 80 mg famotidine (n=28) or placebo (n=27) orally three times a day for 14 consecutive days. Endpoints were time to (primary) or rate of (secondary) symptom resolution, and resolution of inflammation (exploratory). RESULTS: Of 55 patients in the intention-to-treat group (median age 35 years (IQR: 20); 35 women (64%); 18 African American (33%); 14 Hispanic (26%)), 52 (95%) completed the trial, submitting 1358 electronic symptom surveys. Time to symptom resolution was not statistically improved (p=0.4). Rate of symptom resolution was improved for patients taking famotidine (p<0.0001). Estimated 50% reduction of overall baseline symptom scores were achieved at 8.2 days (95% CI: 7 to 9.8 days) for famotidine and 11.4 days (95% CI: 10.3 to 12.6 days) for placebo treated patients. Differences were independent of patient sex, race or ethnicity. Five self-limiting adverse events occurred (famotidine, n=2 (40%); placebo, n=3 (60%)). On day 7, fewer patients on famotidine had detectable interferon alpha plasma levels (p=0.04). Plasma immunoglobulin type G levels to SARS-CoV-2 nucleocapsid core protein were similar between both arms. CONCLUSIONS: Famotidine was safe and well tolerated in outpatients with mild to moderate COVID-19. Famotidine led to earlier resolution of symptoms and inflammation without reducing anti-SARS-CoV-2 immunity. Additional randomised trials are required.