The Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP): Statistical Methods Planned in the Bayesian, Adaptive, Duration Finding Trial.

Abstract

Objectives: To determine the optimal cooling duration for children after out-of-hospital cardiac arrest (OHCA) using an adaptive Bayesian trial design.

Design: The Pediatric Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (P-ICECAP) trial is a randomized, response-adaptive duration/dose-finding clinical trial with blinded outcome assessment. Participants are randomized to one of several cooling durations (0, 12, 18, 24, 36, 48, 60, 72, 84, or 96 hr). The first 150 participants are randomized 1:1:1 to 24-, 48-, and 72-hour durations. Response-adaptive randomization is used thereafter to allocate participants based on emerging duration-response data.

Setting: PICUs.

Patients: Up to 900 pediatric patients 2 days to younger than 18 years old who have survived OHCA and been admitted to an ICU.

Interventions: Duration of targeted temperature management using a surface temperature control device.

Measurements and main results: The primary outcome is the Vineland Adaptive Behavior Scales-Third Edition mortality composite score, assessed at 12 months. Secondary outcomes include changes in the Pediatric Cerebral Performance Category and Pediatric Resuscitation after Cardiac Arrest scores, as well as survival at 12 months. Bayesian modeling is employed to evaluate the duration-response curve and determine the optimal cooling duration. The trial is designed to adaptively update randomization probabilities every 10 weeks, maximizing the allocation of participants to potentially optimal cooling durations. Over 90% power is achieved for the hypothesized scenarios.

Conclusions: The P-ICECAP trial aims to identify the shortest cooling duration that provides the maximum treatment effect for pediatric OHCA patients. The adaptive design allows for flexibility and efficiency in handling various clinical scenarios, potentially transforming pediatric cardiac arrest care by optimizing hypothermia treatment protocols.