ניסוי שלב II של פמוטידין במינון גבוה בחולי COVID-19 שאינם מאושפזים

ממצאים עיקריים

נטילת פמוטידין במינון גבוה (80 מ""ג שלוש פעמים ביום) נמצאה להיות בטוחה ונסבלת היטב בקרב חולים שאינם מאושפזים.

מטופלים עם תסמינים קלים עד בינוניים של COVID-19 אשר נטלו פמוטידין החלימו בקצב מהיר יותר באופן משמעותי.

פמוטידין הוריד את רמות חלבון האינטרפרון מסוג I בדם, דבר שיכול להסביר את מנגנון היעילות שלו נגד COVID-19.

Gut

Publication Date: פברואר 10, 2022
Peer Reviewed: Yes
Publication Type: Original | Clinical Prospective
DOI: https://www.doi.org/10.1136/gutjnl-2022-326952

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, 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.