DESIGN: Prospective, multicentre, double-blind, placebo-controlled trial.

SETTING: Ten acute care hospitals in India.

PARTICIPANTS: Adults <65 years old intended for hospital admission with moderate/severe COVID-19 disease (respiratory rate ≥24 breaths per minute or oxygen saturation ≤93% on room air).

INTERVENTION: DMX-200 120 mg two times per day, or placebo, on background of titratable candesartan commencing at 4 mg two times per day, for 28 days.

MAIN OUTCOME MEASURES: The primary endpoint was COVID-19 disease severity on a modified WHO Clinical Progression Scale (WHO scale) on day 14. Secondary outcomes included the WHO scale at days 28, 60, 90 and 180; intensive care unit (ICU) admission, respiratory failure or death within 28 days; length of hospitalisation; and requirement for ventilatory support or dialysis.

RESULTS: Between December 2021 and August 2022, 518 people were screened, with 49 randomised to DMX-200 or placebo on a background of candesartan. The study was terminated early due to recruitment barriers, including an external requirement to restrict enrolment to adults <65 years old, contributing to a 91% screen failure rate. The median WHO Clinical Progression Scale (WHO scale) score at day 14 for both groups was 1 (IQR 1-1), indicating most participants were discharged with no limitations on activities by this time. Formal comparison was not performed due to the small sample size. One participant receiving DMX-200 died of COVID-19 disease progression. No participants required ICU admission, ventilation or dialysis. Median length of hospitalisation in both groups was 6 days (IQR 6-7 days). WHO scale scores were similar at 28, 60, 90 and 180 days.

CONCLUSION: Due to recruitment barriers, the study was unable to determine whether DMX-200 improves clinical outcomes in people with COVID-19.