Evidence mapPaperPMID 36348276Full record

Trial reportMolecular medicine (Cambridge, Mass.)2022

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

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 and 16 more

Open access · goldAbstract readRandomized Controlled TrialClinical Trial, Phase IIClinical Trial, Phase III
In one paragraph

Trial report in Molecular medicine (Cambridge, Mass.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Links between COVID-19 and Alzheimer's Disease-What Do We Already Know?International journal of environmental research and public health · 2023
    Review
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 5 institutions in 1 country.

Sergio Fragoso-SaavedraPlan de Estudios Combinados en Medicina (MD/PhD Program), Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Isaac NúñezPrograma de Residencia en Medicina Interna, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Belem M Audelo-CruzEscuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, BM, Mexico.
Sarahi Arias-MartínezDepartamento de Neurología y Psiquiatría, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Daniel Manzur-SandovalInstituto Nacional de Cardiología Ignacio Chávez (INCICh), Mexico City, Mexico.
Alejandro Quintero-VillegasPrograma de Residencia en Medicina Interna, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
H Benjamín García-GonzálezPrograma de Residencia en Medicina Interna, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Sergio L Carbajal-MorelosPrograma de Residencia en Medicina Interna, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Sergio PoncedeLeón-RosalesDepartamento de Educación Médica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, Mexico.
José Gotés-PalazuelosPlan de Estudios Combinados en Medicina (MD/PhD Program), Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
José A Maza-LarreaInstituto Nacional de Cardiología Ignacio Chávez (INCICh), Mexico City, Mexico.
J Javier Rosales-de la RosaFacultad de Medicina, Universidad Autónoma de Coahuila, Torreón, Mexico.
Dafne Diaz-RiveraPlan de Estudios Combinados en Medicina (MD/PhD Program), Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Edgar Luna-GarcíaDepartamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
Elvira Piten-IsidroDepartamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
Perla M Del Río-EstradaDepartamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
Mario Fragoso-SaavedraCentro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Departamento de Infectómica y Patogénesis Molecular, Mexico City, Mexico.
Yanink Caro-VegaDepartamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Isabella BatinaDepartamento de Neurología y Psiquiatría, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
León Islas-WeinsteinDepartamento de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
David A Iruegas-NunezDepartamento de Neurología y Psiquiatría, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Juan J CalvaDepartamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Pablo F Belaunzarán-ZamudioDepartamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Juan Sierra-MaderoDepartamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
José C CrispínDepartamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Sergio Iván Valdés-FerrerPlan de Estudios Combinados en Medicina (MD/PhD Program), Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico. sergio.valdesf@incmnsz.mx.ORCID 0000-0002-4863-6484
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán · MXInstituto Nacional de Enfermedades Respiratorias · MXInstituto Nacional de Cardiología · MXInstituto Politécnico Nacional · MXUniversidad Autónoma de Coahuila · MX

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRespiratory 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.

methodsWe 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.

resultsWe 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).

conclusionOur data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.

Indexed as

COVID-19 Drug TreatmentAdultFemaleHumansInflammationMaleMiddle AgedPyridostigmine BromideRespiration, ArtificialSARS-CoV-2Treatment OutcomePyridostigmine BromideAChCOVID-19ImmunomodulationInflammatory reflexInvasive mechanical ventilationMortalityPlacebo-controlled trialPyridostigmineSARS-CoV-2

Identifiers

PMID36348276
PMCPMC9644007
OpenAlexW4308572692

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.