Safety and efficacy of sirolimus in hospitalised patients with COVID-19 pneumonia

Abstract

Background: There is a critical need to develop novel therapies for COVID-19.

Methods: We conducted a phase 2, multicentre, placebo-controlled, double-blind, randomised trial; hospitalised patients with hypoxemic respiratory failure due to COVID-19 and at least one poor prognostic biomarker, were given sirolimus (6 mg on Day 1 followed by 2 mg daily for 14 days or hospital discharge, whichever happens first) or placebo, in a 2:1 randomization scheme favouring sirolimus. Primary outcome was the proportion of patients alive and free from advanced respiratory support measures at Day 28.

Results: Between April 2020 and April 2021, 32 patients underwent randomization and 28 received either sirolimus (n = 18) or placebo (n = 10). Mean age was 57 years and 75 % of the subjects were men. Twenty-two subjects had at least one co-existing condition (Diabetes, hypertension, obesity, CHF, or asthma/COPD) associated with worse prognosis. Mean FiO₂ requirement was 0.35. There was no difference in the proportion of patients who were alive and free from advanced respiratory support measures in the sirolimus group (n = 15, 83 %) compared with the placebo group (n = 8, 80 %). Although patients in the sirolimus group demonstrated faster improvement in oxygenation and spent less time in the hospital, these differences were not statistically significant. There was no between-group difference in the rate of change in serum biomarkers such as LDH, ferritin, d-dimer or lymphocyte count. There was a decreased risk of thromboembolic complications in patients on sirolimus compared with placebo.

Conclusions: Larger studies are warranted to evaluate the role sirolimus in COVID-19 infection.

Keywords: Clinical trial; Rapamycin; SARS-CoV-2; SCOPE; mTOR.