Trial NCT04343963
Publication Fragoso-Saavedra S, medRxiv, 2021 (preprint)
Dates: 2020-05-05 to 2021-01-30
Funding: Public/non profit (Consejo Nacional de Ciencia y Tecnología, Mexico)
Conflict of interest: No
| Methods | |
| RCT Blinding: double blinding | |
| Location :
Multicenter / Mexico Follow-up duration (days): 28 | |
| Inclusion criteria | Hospitalized adults (≥18-year-old) patients with confirmed SARS-CoV-2 infection based on a positive RT-PCR test for SARS-CoV-2 RNA in a respiratory specimen (nasopharyngeal or nasal swab); an imaging study compatible with pneumonia; at least one high-risk criteria of death. |
| Exclusion criteria | Allergy to pyridostigmine; pregnancy or breastfeeding status; concomitant autoimmune disease; diagnosed immunodeficiencies (including HIV infection); need for mechanical ventilation, admission to the ICU, or meeting criteria for septic shock before providing signed, informed consent; inability to receive orally or enterally administered drugs; use of immunosuppressants or immune-modulators (including chemotherapy and corticosteroids) in the preceding 28-day period unless recommended by the treatment medical team as part of the therapeutic approach for SARS-CoV-2 infection; participation in clinical trials of any kind in the previous 28 days. |
| Interventions | |
| Treatment
Pyridostigmine 60 mg orally once a day for 14 days or discharge, mechanical ventilation or death. |
|
| Control
Placebo | |
| Participants | |
| Randomized 188 participants (n1=94 / n2= 94) | |
| Characteristics of participants N=188 Mean age : NR 112 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=188 Critical: n=0 | |
| Primary outcome | |
| In the register Critical condition or death [ Time Frame: 28 days ] Composite of death, Need for mechanical ventilation, or an increase of 2 or more points in the SOFA score ; IL-6 [ Time Frame: 14 days in-hospital, hospital discharge, or death ] Kinetics of circulating IL-6. | |
| In the report A composite of invasive mechanical ventilation (IMV) or death in the 28 days following randomization | |
| Documents available |
Protocol Yes. In English Statistical plan NR Data-sharing stated
|
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment | In addition to the pre-print article, the trial registry and published protocol were used in data extraction and assessment of risk of bias. The study did not achieve the target sample size specified in the trial registry because of the observed difference in the primary outcome between groups after the interim analyses and the difficulty in recruiting new participants. There is no change from the trial registration in the intervention and control treatments. One primary outcome in the registry and protocol (composite of death, Need for mechanical ventilation, or an increase of 2 or more points in the SOFA score) was slightly different in the article (composite of invasive mechanical ventilation or death). |