Abstract
INTRODUCTION: As of November 2021, COVID-19 has killed more than 5 million people globally, including over 750 000 in the USA. Apart from corticosteroids, most available therapeutic options are at best marginally efficient in reducing disease severity and are extremely expensive. The systematic investigation of clinically approved drugs is a priority to determine what does mitigate disease severity. Oestradiol (E2) and progesterone (P4) produce a state of anti-inflammatory immune responses and immune tolerance, and enhanced antibody production. The goal of this trial is to evaluate the efficacy of a short E2 and P4 therapy, in addition to standard of care (SOC), in mitigating disease severity in COVID-19 hospitalised patients. METHODS AND ANALYSIS: Phase 2, randomised, double blind, placebo-controlled, single-centre trial. Patients hospitalised for confirmed COVID-19, with scores 3-5 on the 9-point WHO ordinal scale are randomised between two arms: (1) Oestradiol cypionate intramuscular (IM) and micronised progesterone oral (PO), in addition to SOC, and (2) placebo, in addition to SOC. The primary outcome is the proportion of patients improving to scores 1 or 2 on the WHO scale through day 28. Secondary outcomes include length of hospital stay, duration of mechanical ventilation, cause of death, readmission rates, change in inflammatory biomarkers between admission and occurrence of primary endpoint, and adverse events. Study sample size will be up to 120 participants. The trial is currently recruiting subjects. ETHICS AND DISSEMINATION: The sponsor of this study is the Center of Excellence in Sex-Based Biology & Medicine at Tulane University, New Orleans, Louisiana, USA. Ethical approval was obtained from the Tulane institutional review board on 14 May 2021. The study was reviewed by the US Food and Drug Administration and granted Investigational New Drug #152 499. Results of the study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04865029; Pre-results.