The Danish Out-of-Hospital Cardiac Arrest Trial: A Statistical Analysis Plan

Area of Science:

• Critical Care Medicine
• Clinical Trials Methodology
• Cardiology

Background:

• Optimal post-cardiac arrest care strategies remain uncertain for reducing morbidity and mortality.
• The Danish Out-of-Hospital Cardiac Arrest (DANOHCA) trial investigates four interventions: high-dose dexamethasone, prophylactic olanzapine, elevated backrest, and early wakeup.
• This manuscript outlines the statistical analysis plan for these interventions in a factorial trial.

Purpose of the Study:

• To present the complete statistical analysis plan for the DANOHCA trial.
• To define primary and secondary outcomes, covariate adjustment, and data handling procedures.
• To ensure a transparent and rigorous framework for analyzing intervention effects.

Main Methods:

• A 2x2x2x2 factorial randomized clinical trial enrolling comatose adult out-of-hospital cardiac arrest patients.
• Co-randomization to dexamethasone vs. placebo, olanzapine vs. placebo, backrest elevation (35° vs. 5°), and early vs. late wakeup.
• Intention-to-treat principle for primary analyses, with finalized plan before randomization completion.

Main Results:

• Primary outcomes include 90-day mortality (dexamethasone, backrest) and 30-day days alive outside hospital (olanzapine, wakeup).
• Secondary endpoints encompass later mortality, neurological function, quality of life, organ function, and safety.
• Statistical methods include mixed-effects regression, Cox regression, and nonparametric tests with sensitivity analyses.

Conclusions:

• This statistical analysis plan provides a detailed and transparent framework for the DANOHCA trial.
• It guides the primary analyses and reporting of intervention effects.
• Ensures methodological rigor and comparability across interventions.