Prophylactic Olanzapine Versus Placebo in Comatose Survivors of Out‐of‐Hospital Cardiac Arrest: Protocol for a Multicenter Randomized Comparison Within the Danish Out‐of‐Hospital Cardiac Arrest (
DANOHCA
Benedikte Liebetrau, Anders M. Grejs, Martin A. S. Meyer, Lars P. K. Andersen, Sören Möller, Simon Mølstrøm, Jacob E. Møller, Henrik Schmidt, Steffen Christensen, Jesper Kjærgaard, Christian Hassager, Bodil S. Rasmussen, Jo B. Andreasen ABSTRACT
Background
Delirium is a frequent complication in comatose Out‐of‐Hospital Cardiac Arrest (OHCA) survivors requiring postresuscitation intensive care and is associated with higher mortality and longer hospitalization. Despite this, there is no established pharmacologic strategy for delirium prevention in OHCA survivors. This trial aims to evaluate if prophylactic use of olanzapine in comatose OHCA patients can reduce delirium incidence, thereby leading to a shorter duration of hospitalization.
Methods
The Danish Out‐of‐Hospital Cardiac Arrest (DANOCHA) trial is an investigator‐initiated, multicenter, randomized, controlled trial evaluating four postresuscitation interventions in adult patients resuscitated after OHCA including administration of prophylactic olanzapine compared with placebo. Comatose adult patients with OHCA of presumed cardiac cause and sustained return of spontaneous circulation (> 20 min) will be randomized 1:1 to receive either 10 mg of olanzapine or placebo immediately after inclusion in the trial and the two following evenings for a total of three doses. The primary outcome is days alive and out of the hospital within 30 days after admission. Analysis of primary outcome will be analyzed using the Wilcoxon rank‐sum test. Results will be presented as medians with interquartile ranges and 95% confidence intervals for the median difference. Inclusion began in June 2023, and the study aims to include 1000 patients from five sites over an estimated time period of 3–4 years. The trial is registered at clinicaltrials.gov (identifier: NCT05895838) and euclinicaltrials.eu (2024‐515997‐28‐00).
Perspectives
Optimizing postresuscitation care through large‐scale randomized trials is essential for improving outcomes of OHCA survivors. The findings from this part of the DANOHCA trial will provide evidence regarding the effects of prophylactic olanzapine in comatose OHCA survivors.
Trial Registration:
EudraCT no 2016‐003265‐26; EU CTIS no 2024‐515997‐28‐00;