A pilot study on intravenous N-Acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome
Abbas Taher, Marjan Lashgari, Ladan Sedighi, Farshid Rahimi-Bashar, Jalal Poorolajal, Maryam Mehrpooya
Pharmacological Reports, doi:10.1007/s43440-021-00296-2
Background We designed this single-centre clinical trial to assess the potential benefits of N-Acetylcysteine (NAC) in patients with COVID19-associated acute respiratory distress syndrome (ARDS). Methods Ninety-two patients with mild-to-moderate COVID19-associated ARDS were allocated to the placebo (45-cases) or NAC groups (47-cases). Besides standard-of-care treatment, the patients received either intravenous NAC at a dose of 40 mg/kg/day or the placebo for three consecutive days. The efficacy outcomes were overall mortality over 28-day, clinical status on day 28, based on the WHO Master Protocol, the proportion of patients requiring mechanical ventilation, changes in ARDS-severity (based on the PaO 2 /FiO 2 ratio), and Sequential Organ Failure Assessment (SOFA) scores 48 and 96 h after intervention, Results No differences were found in the 28-day mortality rate between the two groups (25.5% vs. 31.1% in the NAC and placebo groups, respectively). Although the distribution of the clinical status at day 28 shifted towards better outcomes in the NAC-treated group, it did not reach a statistical significance level (p value = 0.83). Similar results were achieved in terms of the proportion of patients who required invasive ventilator support (38.3% vs. 44.4%), the number of ventilator-free days (17.4 vs. 16.6), and median time of ICU and hospital stay. Results regarding the change in PaO 2 /FiO 2 ratio and SOFA scores also showed no significant differences between the groups. Conclusions Our pilot study did not support the potential benefits of intravenous NAC in treating patients with COVID-19-associated ARDS. More studies are needed to determine which COVID-19 patients benefit from the NAC administration. Trial registration The trial was registered at Clinicaltrials.gov (identifier code: IRCT20120215009014N355). Registration date: 2020-05-18.
Author contributions Conceptualisation: AT, MM; methodology: AT, MM, JP; data acquisition: AT, LS, ML, FR-B; statistical analysis: MM, JP; writing-original draft preparation: LS; writing-review and editing: MM, AT; all authors contributed to the interpretation of the results and read and approved the final manuscript.
Conflict of interest The authors declare that they have no competing interests.
Ethical approval and consent to participate The trial protocol was according to the Declaration of Helsinki as revised in 1989, and the study protocol was approved by the research and ethics committee at Hamadan University of Medical Sciences (IR.UMSHA. REC.13999.153).
Consent for publication All authors have given consent for publication.
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