A parallel-group, multicenter randomized, double-blinded, placebo-controlled, phase 2/3, clinical trial to test the efficacy of pyridostigmine bromide at low doses to reduce mortality or invasive mechanical ventilation in adults with severe SARS-CoV-2 infection: the Pyridostigmine In Severe COvid-19 (PISCO) trial protocol

BMC Infectious Diseases

Yanink Caro-Vega¹  Juan Sierra-Madero¹  Verónica Luqueño-Martínez¹  Juan José Calva¹  Brenda Crabtree-Ramírez¹  Pablo F. Belaunzarán-Zamudio²  Sarahi Arias-Martínez³  Belem M. Audelo-Cruz³  Alejandra González-Duarte³  Sergio I. Valdés-Ferrer⁴  David A. Iruegas-Nunez⁵  José C. Crispín⁶  Sergio L. Carbajal-Morelos⁷  H. Benjamín García-González⁷  Isaac Nuñez⁷  Alejandro Quintero-Villegas⁷  Sergio Fragoso-Saavedra⁸ 

[1] Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA;Departamento de Neurología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;Departamento de Neurología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;Center for Biomedical Science, Feinstein Institute for Medical Research, Manhasset, NY, USA;Departamento de Neurología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;Escuela Nacional de Medicina y Ciencias de la Salud, Instituto Tecnológico y de Destudios Superiores de Monterrey, Monterrey, Mexico;Departamento de e Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;Internal Medicine Residency Training Program, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;Programa de Estudios Combinados en Medicina (MD/PhD program), Universidad Nacional Autónoma de Mexico, Mexico City, Mexico;Departamento de Neurología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;

关键词: COVID-19;    SARS-Cov-2;    Mortality;    Invasive mechanical ventilation;    Immunomodulation;    Pyridostigmine;    ACh;    Inflammatory reflex;    Placebo-controlled trial;   

DOI  :  10.1186/s12879-020-05485-7

来源: Springer

【 摘 要 】

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic inflammatory response, pulmonary damage, and even acute respiratory distress syndrome (ARDS). This in turn may result in respiratory failure and in death. Experimentally, acetylcholine (ACh) modulates the acute inflammatory response, a neuro-immune mechanism known as the inflammatory reflex. Recent clinical evidence suggest that electrical and chemical stimulation of the inflammatory reflex may reduce the burden of inflammation in chronic inflammatory diseases. Pyridostigmine (PDG), an ACh-esterase inhibitor (i-ACh-e), increases the half-life of endogenous ACh, therefore mimicking the inflammatory reflex. This clinical trial is aimed at evaluating if add-on of PDG leads to a decrease of invasive mechanical ventilation and death among patients with severe COVID-19.MethodsA parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19.DiscussionThis study will provide preliminary evidence of whether or not -by decreasing systemic inflammation- add-on PDG can improve clinical outcomes in patients with severe COVID-19.Trial registrationClinicalTrials.gov NCT04343963 (registered on April 14, 2020).

【 授权许可】

CC BY