학술논문
Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial
Document Type
article
Author
Sergio Fragoso-Saavedra; Isaac Núñez; Belem M. Audelo-Cruz; Sarahi Arias-Martínez; Daniel Manzur-Sandoval; Alejandro Quintero-Villegas; H. Benjamín García-González; Sergio L. Carbajal-Morelos; Sergio PoncedeLeón-Rosales; José Gotés-Palazuelos; José A. Maza-Larrea; J. Javier Rosales-de la Rosa; Dafne Diaz-Rivera; Edgar Luna-García; Elvira Piten-Isidro; Perla M. Del Río-Estrada; Mario Fragoso-Saavedra; Yanink Caro-Vega; Isabella Batina; León Islas-Weinstein; David A. Iruegas-Nunez; Juan J. Calva; Pablo F. Belaunzarán-Zamudio; Juan Sierra-Madero; José C. Crispín; Sergio Iván Valdés-Ferrer
Source
Molecular Medicine, Vol 28, Iss 1, Pp 1-11 (2022)
Subject
Language
English
ISSN
1076-1551
1528-3658
1528-3658
Abstract
Abstract: Background: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. Methods: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. Results: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44–64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24–0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). Conclusion: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.