Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial

• Main Authors: Sergio Fragoso-Saavedra (Author), Isaac Núñez (Author), Belem M. Audelo-Cruz (Author), Sarahi Arias-Martínez (Author), Daniel Manzur-Sandoval (Author), Alejandro Quintero-Villegas (Author), H. Benjamín García-González (Author), Sergio L. Carbajal-Morelos (Author), Sergio PoncedeLeón-Rosales (Author), José Gotés-Palazuelos (Author), José A. Maza-Larrea (Author), J. Javier Rosales-de la Rosa (Author), Dafne Diaz-Rivera (Author), Edgar Luna-García (Author), Elvira Piten-Isidro (Author), Perla M. Del Río-Estrada (Author), Mario Fragoso-Saavedra (Author), Yanink Caro-Vega (Author), Isabella Batina (Author), León Islas-Weinstein (Author), David A. Iruegas-Nunez (Author), Juan J. Calva (Author), Pablo F. Belaunzarán-Zamudio (Author), Juan Sierra-Madero (Author), José C. Crispín (Author), Sergio Iván Valdés-Ferrer (Author)
• Format: Book
• Published: BMC, 2022-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

10.1186/s10020-022-00553-x
1076-1551
1528-3658