Eritoran and Apremilast in hospitalized patients with COVID-19: the REMAP-CAP Immune Modulation-2 Domain

Objectives : Eritoran, a TLR4 antagonist, and apremilast, a PDE4 inhibitor, were considered therapeutic candidates for COVID-19. The study aim was to evaluate their safety and efficacy of among COVID-19 patients. Methods : A randomized controlled trial was conducted among hospitalized patients with COVID-19 within the Randomized, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP). The primary outcome was organ support-free days (OSFD), an ordinal composite outcome combining death (assigned a label of -1) and days free from organ support through day 21. A Bayesian ordinal model was applied for statistical analysis. Results : The trial was terminated early due to slow recruitment, before pre-specified stopping criteria were met. Among 104 patients enrolled in the double-blind phase (101 noncritically ill, 3 critically ill; median age, 59 years; 47.1% female), 46, 6 and 52 were randomized to eritoran, apremilast, and placebo, respectively. The median OSFD was 22 days in both the eritoran and control groups (interquartile range, 22 to 22) (adjusted odds ratio of 1.01 (95% credible interval, 0.34 to 2.90); posterior probability of superiority of 50.6%). The apremilast comparison was not feasible due to insufficient enrollment. Five serious adverse events were reported among 51 patients receiving eritoran, of which four were considered unrelated to eritoran. No serious adverse events were reported in the apremilast arm. Conclusions : This trial was inconclusive to determine the efficacy of eritoran because of early termination. Enrollment was insufficient to evaluate apremilast. No new safety signals were identified, although the small sample size limits conclusions regarding safety. Clinical Trial Registration : NCT02735707 and jRCT2031200443