Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Abstract

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome.

Fig. 1. Trial profile.

* Number recruited overall at sites participating in the DMF comparison during the period that adult participants could be recruited. DMF unavailable and DMF unsuitable are not mutually exclusive.

Fig. 2. Distribution of clinical ordinal scale at 5 days by randomised allocation.

Percentages of participants in each ordinal category at day 5 are shown.

Fig. 3. Effects of allocation to dimethyl fumarate on relative odds of a bad outcome on the clinical ordinal scale at day 5, for each alternative definition of bad outcome.

Odds ratio estimates for each ordinal scale comparison are represented by squares (with areas of the squares proportional to the amount of statistical information) and the lines through them correspond to the 95% CIs. Estimates used ordinal logistic regression with adjustment for baseline score. P value is 2-sided. OR odds ratio.