Dexamethasone Versus Placebo in Comatose Survivors of Out‐of‐Hospital Cardiac Arrest: Study Protocol for a Multicenter Randomized Comparison Within the Danish Out‐of‐Hospital Cardiac Arrest Trial ( <scp>DANOHCA</scp> )

BACKGROUND: The inflammatory response to whole-body ischemia, as seen in comatose survivors after out-of-hospital cardiac arrest (OHCA), is associated with increased morbidity and mortality. Early high-dose dexamethasone may dampen the inflammatory response, which may diminish secondary brain damage and other organ injury and decrease mortality. The aim is to evaluate the effect of high-dose dexamethasone in post-resuscitation care. METHODS: The Danish Out-of-Hospital Cardiac Arrest (DANOHCA) trial is an investigator-initiated, multicenter, randomized, controlled trial evaluating four post-resuscitation interventions in adult patients resuscitated after OHCA including blinded early administration of high-dose dexamethasone compared with placebo (isotonic saline). Adult OHCA patients with presumed cardiac etiology and sustained return of spontaneous circulation will be randomized 1:1 to receive 20 mg of dexamethasone or placebo immediately after inclusion in the trial and repeated the following two mornings for a total of three doses. The primary outcome is all-cause mortality within 90 days using a log-binomial regression analysis to estimate the relative risk of death from any cause between randomization and Day 90. Enrollment began in June 2023, with the aim to include 1000 patients at five sites in 3-4 years. The trial is registered at clinicaltrials.gov (identifier: NCT05895838) and euclinicaltrials.eu (2024-515997-28-00). PERSPECTIVES: It is of paramount importance to optimize post-resuscitation care through large-scale randomized trials. Global ischemia-reperfusion-induced inflammatory response with resulting organ failures represents a possible target for interventions after OHCA. This part of the DANOHCA trial will provide new evidence on the impact of high-dose dexamethasone in survivors of OHCA. TRIAL REGISTRATION: Clinical Trials Information System (CTIS): 2024-515997-28-00.