A pilot study on intravenous N-Acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome

Abstract

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.

Use of Thiols in the Treatment of COVID-19: Current Evidence

“…Another study that enroled 92 patients with COVID-19-associated ARDS was unable to find difference in the 28-day mortality rate between the group treated with NAC at an intravenous dose of 40 mg/kg/day as an adjunct therapy (25.5%) and that treated with placebo (31.1%) [72].…”

Changes in Glycolytic Pathway in SARS-COV 2 Infection and Their Importance in Understanding the Severity of COVID-19

“…Beneficial effects of N-acetylcysteine have been demonstrated in clinical trials in various infections, including influenza and influenza-like infections, namely H1N1 influenza pneumonia or even community acquired pneumonia (De Flora et al, 1997;Zhang et al, 2018). In COVID-19, administration of N-acetylcyteine, alone or together with other types of supplementation may be beneficial in patients with different degrees of severity of SARS-CoV-2 infection, as suggested by a few small-sized, non-controlled clinical interventional studies or case reports (De Flora et al, 2020;Avdeev et al, 2021;Wong et al, 2021), although these results may not apply to patients with SARS-CoV-2-induced ARDS (de Alencar et al, 2021;Taher et al, 2021), and still need to be more robustly analysed in larger, randomised, placebo-controlled studies.…”

Combinations of drugs might increase the survival chances of COVID-19 patients: Literature review till date

“…Taher et.al conversely reported that IV-NAC administration showed positive impact but did not show significant results in the treatment of critical COVID-19 patients [1003]. Taher et.al in their study of 92 patients administered 47 patients with IV-NAC and treated the other 45 people as placebo.…”

“…Taher et.al in their study of 92 patients administered 47 patients with IV-NAC and treated the other 45 people as placebo. These patients were followed up for 28 days [1003]. But in the study Taher et.al [1003] have followed only a 3-day treatment protocol [1003].…”

“…These patients were followed up for 28 days [1003]. But in the study Taher et.al [1003] have followed only a 3-day treatment protocol [1003]. We have already seen in the above successful study of Ibrahim et.al [9] that temporary/single time administration of NAC can only produce temporary results by suppressing inflammatory responses temporarily when administered in critical COVID-19 patient [1003].…”