UH3HL159134

1/2 Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP) - Project Summary

Out-of-hospital cardiac arrest (OHCA) in children is a tragic event that usually results in death or permanent brain injury in survivors. More than 7000 children suffer OHCA each year in the US, and improvements in pediatric OHCA outcomes, just as in adults, are very much limited by our ability to protect the brain from global cerebral ischemic injury in those who are successfully resuscitated.

Targeted temperature management (TTM) is currently guideline-recommended in children following OHCA, with preference stated for therapeutic hypothermia (TTM 32-34°C) over normothermia (TTM 36-37.5°C) in order to prevent fever, which could amplify brain injury. The optimal duration and patient selection criteria for therapeutic hypothermia in children remain unknown, and cooling devices are not specifically FDA approved for this indication.

Preclinical data and mechanistic studies strongly suggest that durations of hypothermia longer than those typically used in adults may minimize brain injury. This study will determine if identifying an optimal duration (dose) of therapeutic hypothermia can improve outcomes, and if the development of a duration response curve can confirm efficacy in a wider pediatric population of OHCA survivors.

We hypothesize that longer durations of cooling will improve survival and result in better neurologic recovery in survivors compared to shorter cooling durations, as assessed by the Vineland Adaptive Behavior Scales–Third Edition (Vineland-3) score. The primary goal of this project is to identify clinical strategies that will increase the number of patients with improved neurological recovery from OHCA.

The results of this trial will be extremely significant in children and will immediately impact both clinical practice and regulatory evaluation. The Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP) trial, modeled after the ongoing adult ICECAP trial, uses innovative adaptive dose finding methods that allow exploration of a wide range of potential durations and efficiently allocate subjects where they will be most informative.

The study will be conducted using resources of the NHLBI/NINDS Strategies to Innovate Emergency Care Clinical Trials Network (SIREN), which is experienced in both pediatric and adult trials and is currently conducting the current adult ICECAP trial. SIREN leverages existing resources to achieve economies of scale and to conduct important clinical investigations spanning from pre-hospital, through both the emergency department and ICU stay, and post-hospital discharge.

Regents Of The University Of Michigan

NOT APPLICABLE

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Ann Arbor, Michigan 481091276 United States

Single Zip Code

Clinical Coordinating Center for Multi-Site Investigator-Initiated Clinical Trials (Collaborative UG3/UH3 Clinical Trial Required) (PAR-19-329)

Amendment Since initial award the total obligations have increased 323% from $3,248,612 to $13,729,037.