Stabilised, synthetic sulforaphane in hospitalized patients with suspected COVID-19 pneumonia: a double-blind, placebo-controlled RCT

ABSTRACT

Introduction: The transcription factor Nrf2 downregulates key inflammatory cytokines in COVID-19 (IL-6, IL-1b, COX-2 and TNF-a). We investigated the efficacy of S-SFN (stabilised sulforaphane, activator of Nrf2) to improve clinical outcomes in patients hospitalized with suspected COVID-19. Method(s) Randomized, double-blind, placebo-controlled trial, patients hospitalised with suspected or confirmed COVID-19, radiological pneumonia and a CURB65 score of >= 1 were randomized 11 to once-daily S-SFN 300mg or placebo for 14 days. The primary outcome was the 7-point WHO Clinical Status (CS) scale at day 15. Key secondary outcomes included time to clinical improvement, national early warning score (NEWS), oxygen and ventilation use, and mortality. Result(s) The trial was terminated due to futility after 133 patients had been enrolled (S-SFN, n=65 and placebo, n=68). 103 had PCR confirmed COVID-19 infection. S-SFN treatment was not associated with improved CS at day 15 (OR 0.87 95%CI (0.41-1.83, p=0.712). There was no difference in time to clinical improvement (HR 1.02 (0.70- 1.49)). S-SFN was not associated with a reduced length of hospital stay (6.2days vs 7.4days (S-SFN)). There were 26 deaths during the 29-day follow-up, 11 (16.2%) and 15 (23.1%) patients died in the placebo and S-SFN treated groups respectively (HR 1.45 (0.67-3.16)). There were no differences between treatment groups with respect to oxygen or ventilation free days. Adverse events were reported in 44.1% of placebo treated and 64.6% of S-SFN treated patients. Conclusion(s) S-SFN treatment did not improve day 15 clinical status in hospitalized patients with suspected or confirmed COVID-19 infection.