Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial
Christina M Brennan, Sandeep Nadella, Xiang Zhao, Richard J Dima, Nicole Jordan-Martin, Breanna R Demestichas, Sam O Kleeman, Miriam Ferrer, Eva Carlotta Von Gablenz, Nicholas Mourikis, Michael E Rubin, Harsha Adnani, Hassal Lee, Taehoon Ha, Soma Prum, Cheryl B Schleicher, Sharon S Fox, Michael G Ryan, Christina Pili, Gary Goldberg, James M Crawford, Sara Goodwin, Xiaoyue Zhang, Jonathan B Preall, Ana S H Costa, Joseph Conigliaro, Joseph R Masci, Jie Yang, David A Tuveson, Kevin J Tracey, Dr Tobias Janowitz
Gut, doi:10.1136/gutjnl-2022-326952
Objective We assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19. Design Randomised, double-blind, placebocontrolled, 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.
INTRODUCTION The search for safe, effective and affordable treatments for COVID-19 remains a global health priority. COVID-19 is pandemic, with an estimated 319 M cases and 5.5 M deaths worldwide to date. Restrictive public health measures in response to COVID-19 have led to unprecedented negative impacts on society. 2 COVID-19 is caused by the SARS-CoV-2. On body entry, SARS-CoV-2 docks to the widely expressed ACE2 4 5 and is internalised into the cell. Viral replication causes cell death and engages the immune system. 8 Toll-like receptor 3 (TLR3) binds
Significance of this study What is already known on this subject? ► COVID-19 is caused by the SARS-CoV-2. ► Cytokine release drives inflammation and poor outcome in patients with COVID-19. ► Famotidine is a histamine 2 receptor antagonist that is globally used to reduce gastric reflux symptoms and treat gastric ulcers. ► In laboratory studies, famotidine reduced type-I interferon release from virally infected epithelial cells. ► Famotidine improved the outcome of patients with COVID-19 in some retrospective studies and a case series, but evidence from a clinical trial is lacking.
What are the new findings? ► In this randomised,..
Intestinal inflammation the experimental medicine part of the study. DAT and TJ secured funding. All authors read, edited and approved the final manuscript. Competing interests None declared.
Patient consent for publication Not applicable. Ethics approval This study involves human participants and was approved by The Northwell Health Institutional Review Board IRB#: 20-1155. Participants gave informed consent to participate in the study before taking part. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data are available upon reasonable request. The gene list for assessing type-I interferon response is provided in Table S5 . Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
Open access This is an open access article distributed in accordance with the Creative Commons..
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