Double-blind, randomized, placebo-controlled trial with N-acetylcysteine for treatment of severe acute respiratory syndrome caused by COVID-19

Clin Infect Dis. 2020 Sep 23;ciaa1443. doi: 10.1093/cid/ciaa1443. Online ahead of print.


Background: A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by SARS-CoV-2 may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in Covid-19 patients.

Objective: To determine whether NAC in high doses can avoid respiratory failure in patients with Covid-19.

Methods: It was a double-blind, randomized, placebo-controlled, unicentric trial, conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil. We enrolled 135 patients with severe Covid-19 (confirmed or suspected), with an oxyhemoglobin saturation of less than 94% or respiratory rate higher than 24 breaths/min. Patients were randomized to receive NAC 21 g (approximately 300 mg/kg) for 20 hours, or dextrose 5%. Primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to ICU, time in ICU, and mortality.

Results: Baseline characteristics were very similar in the two groups, with no significant difference in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest CT scan findings. Sixteen patients (23.9%) in the Placebo group were submitted to endotracheal intubation and mechanical ventilation, compared to 14 patients (20.6%) in the NAC group (p=0.675). No difference was observed in secondary endpoints.

Conclusion: Administration of NAC in high doses did not affect the evolution of severe Covid-19.

Keywords: Angiotensin; Mechanical ventilation; Pneumonia.