Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials

Abstract

Objective: To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials.

Design: Multicenter randomized controlled trials.

Setting: Pediatric intensive care and cardiac ICUs in the United States and Canada.

Patients: Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent.

Interventions: Therapeutic hypothermia or therapeutic normothermia.

Measurements and main results: From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015.

Conclusions: Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials.

Trial registration: ClinicalTrials.gov NCT00878644 NCT00880087.

Figure 1

Site distribution map of the United States and Canada. See Appendix 1 for site with site investigator listing.

Figure 2

Overview of Therapeutic Hypothermia after Pediatric Cardiac Arrest trials.

Figure 3

Therapeutic hypothermia and therapeutic normothermia temperature timeline 0–120 hr. Dashed and dotted line = normothermia group; dotted line = hypothermia group. Intervals: a = time from randomization to assigned temperature range; b = 48hr of assigned temperature; c = rewarming of hypothermia group; d = interval of controlled normothermia in both groups.