Abstract

Aim: This study is aimed at evaluating the efficacy and safety of Intravenous Glutathione in moderate COVID-19 patients with respiratory distress.

Study Design: A randomized, multicentric, double-blind, placebo-controlled, comparative Phase III clinical trial.

Place and Duration of Study: This clinical trial was conducted at 7 geographically distributed sites across India between February 2021 to September 2021.

Participants: The study enrolled 240 participants who were tested and confirmed cases of moderate COVID-19 with respiratory distress.

Interventions: Intravenous glutathione (GSH) at a loading dose of 2400 mg on the first day, followed by a dose of 1200 mg every 12 hours for seven days.

Methodology: Patients were randomized into two groups in a ratio of 1:1, to receive either glutathione or placebo. Both the study drugs were given as an addition to the standard of care (SOC). The study site staff, investigator and patients were blinded to the treatment allocation. The primary endpoint of the study was two or more points of improvement on the WHO 7-point ordinal scale whereas the secondary endpoints were the proportion of patients not requiring oxygen supplementation after treatment. Other secondary endpoints included the proportion of patients who changed from a higher to a lower score on the WHO 7-Point ordinal scale, the proportion of patients remaining hospitalized, the need of non-invasive ventilation or new requirement of high flow oxygen use, and incidences of adverse events.

Results: A significant clinical improvement in the GSH group (p<0.001) was observed in early treatment days. On day 3, GSH group had improvement in 49.15% of the patients as compared to 31.96% on placebo (p=0.007; odds ratio, 2.06; 95% CI, 1.22-3.48). A higher proportion of patients with baseline score of 5 or more in the GSH group (64.63%) showed improvement as compared to the placebo (46.58%) (p=0.024; odds ratio, 2.10; 95% CI, 1.10-4.00). A higher proportion of patients in the GSH group attained a score of 3 or less signifying no need of Oxygen supplementation, as compared to the placebo group on Day 2, Day 3 and Day 4. A reduction of severity in clinical status was also observed on Day 3, Day 4 and Day 5. The risk of remaining in the hospital was reduced by 37% in the GSH group. The 7-day dose of GSH was well tolerated by the patients.

Conclusion: GSH supplementation reduces the cytokine storm and respiratory distress in patients with COVID-19 pneumonia. GSH can also be used for treating respiratory distress due to other etiologies due to its favorable safety profile. GSH treatment should also be explored in a larger number of patients with ARDS of varied etiologies in randomized trials.