Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial
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Published:2022-11-08
Issue:1
Volume:28
Page:
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ISSN:1076-1551
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Container-title:Molecular Medicine
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language:en
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Short-container-title:Mol Med
Author:
Fragoso-Saavedra Sergio, Núñez Isaac, Audelo-Cruz Belem M., Arias-Martínez Sarahi, Manzur-Sandoval Daniel, Quintero-Villegas Alejandro, Benjamín García-González H., Carbajal-Morelos Sergio L., PoncedeLeón-Rosales Sergio, Gotés-Palazuelos José, Maza-Larrea José A., Rosales-de la Rosa J. Javier, Diaz-Rivera Dafne, Luna-García Edgar, Piten-Isidro Elvira, Del Río-Estrada Perla M., Fragoso-Saavedra Mario, Caro-Vega Yanink, Batina Isabella, Islas-Weinstein León, Iruegas-Nunez David A., Calva Juan J., Belaunzarán-Zamudio Pablo F., Sierra-Madero Juan, Crispín José C., Valdés-Ferrer Sergio IvánORCID
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.
Funder
Consejo Nacional de Ciencia y Tecnología
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics,Molecular Biology,Molecular Medicine
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