{Reference Type}: Randomized Controlled Trial
{Title}: Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial.
{Author}: Fragoso-Saavedra S;Núñez I;Audelo-Cruz BM;Arias-Martínez S;Manzur-Sandoval D;Quintero-Villegas A;Benjamín García-González H;Carbajal-Morelos SL;PoncedeLeón-Rosales S;Gotés-Palazuelos J;Maza-Larrea JA;Rosales-de la Rosa JJ;Diaz-Rivera D;Luna-García E;Piten-Isidro E;Del Río-Estrada PM;Fragoso-Saavedra M;Caro-Vega Y;Batina I;Islas-Weinstein L;Iruegas-Nunez DA;Calva JJ;Belaunzarán-Zamudio PF;Sierra-Madero J;Crispín JC;Valdés-Ferrer SI;
{Journal}: Mol Med
{Volume}: 28
{Issue}: 1
{Year}: 11 2022 8
{Factor}: 6.376
{DOI}: 10.1186/s10020-022-00553-x
{Abstract}: 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.<BR>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.<BR>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).<BR>Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.