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.

Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children

“…14 We report results of the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial, which compared the efficacy of therapeutic hypothermia (target temperature, 33.0°C) with that of therapeutic normothermia (target temperature, 36.8°C). 15,16 …”

Dilemmas in undertaking research in paediatric intensive care

“…This can lead to underpowered, negative RCTs. Therapeutic hypothermia for paediatric in-hospital cardiac arrest (THAPCA-IH) trial has not yet completed recruitment a decade after study conceptualisation 35. Technological advances, evolution of standard therapy and shifts in clinicians’ perception of equipoise during such long periods also add to the difficulties in performing RCTs.…”

Evolution, safety and efficacy of targeted temperature management after pediatric cardiac arrest

“…37 This effect was observed with a fourfold increase in PICU length of stay for TTM (32-34 • C) patients who eventually died compared to STM nonsurvivors. The inclusion of only OHCA patients may explain the comparative shorter length of stay for STM patients (1.3 days) compared to Doherty et al 11 (9.0 days (IQR [5.0-22.3])) and Fink et al 10 (5 days (IQR [1][2][3][4][5][6][7][8][9][10][11][12][13][14])). A temporal trend of increasing time to withdrawal of intensive care support and death along with an increased use of MRI and EEG investigations was also noted.…”

“…arrest (NCT00880087) investigating TTM at 33 • C for 48 h versus TTM at 36.7 • C are on-going. 8,9 Pediatric retrospective studies of TTM have been limited. [10][11][12] Two studies showed no difference in survival outcome with TTM (33-34 • C) versus the institutions usual standard temperature management (STM).…”