Hypothermia for Cardiac Arrest in Paediatrics
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Hypothermia for Cardiac Arrest in Paediatrics (HypCAP) - Pilot Study|
- The percentage of children achieving a "good outcome", that is, a PCPC of 1-3 will be assessed using the Paediatric Cerebral Performance Category scores [ Time Frame: Assessed at 12 months post cardiac arrest ] [ Designated as safety issue: No ]
- Cognitive and motor measures [ Time Frame: Assessed at 12 months post-arrest ] [ Designated as safety issue: No ]
- Mortality [ Time Frame: Assessed at 1, 3, 6, and 12 months post-arrest ] [ Designated as safety issue: Yes ]
- Cerebral edema [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Adverse effects of hypothermia therapy [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2005|
|Study Completion Date:||September 2010|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
|Active Comparator: 1||
Patients randomized to the Normothermia arm (esophageal temp 36.5-37.5 ºC) will be maintained at an esophageal temperature of 36.5-37.5ºC for 48 hours. Patients who are hypothermic (temperature < 35 ºC) when randomized to the normothermia group will be rewarmed slowly using the servo-controlled mattress. Patients who are hyperthermic following randomization to the normothermia group will be actively cooled to normothermia using the servo-controlled mattress. Neuromuscular blockers will be administered as needed intravenously in both groups of patients to prevent shivering.
Patients randomized to the Hypothermia arm (esophageal temp 33º to 34 °C) will be cooled rapidly using the cooling protocol developed for the Hypothermia Paediatric Head Injury Trial. A temperature probe will be placed in the esophagus and its position confirmed using a chest radiograph. Patients will be placed on a servo-controlled cooling blanket and covered in crushed ice (in sealed plastic bags covered by pillow cases) and a second cooling blanket. Once the esophageal temperature reaches 34.0ºC, the ice and second cooling blanket will be removed and esophageal temperature will be maintained at 33º to 34 °C for 48 hours using the servo-controlled cooling mattress. Patients treated with ECMO will be cooled using the extracorporeal circuit cooling-device. Rewarming will be done at a rate of 0.5 ºC every 2 hours until an esophageal temperature of 36.5 ºC is reached. Thereafter temperature will be recorded but not controlled by surface cooling.
Cardiac arrest is associated with a high morbidity and mortality in children and hypothermia therapy has the potential to be beneficial in children following cardiac arrest. We have a track record of both clinical and laboratory research of hypothermia therapy following cardiac arrest at the Hospital for Sick Children and have begun a 3-site randomized controlled pilot study of hypothermia therapy following cardiac arrest in children funded by The Hospital for Sick Children Research Institute and the Heart and Stroke Foundation of Ontario. We are currently expanding the study to an 11 site pilot study with bridge funding from the American Heart Association.
Recently two trials were published in the New England Journal of Medicine demonstrating the efficacy of 12 hours and 24 hours of hypothermia therapy following ventricular arrhythmia-induced cardiac arrest in adults. The results of these important studies suggest that hypothermia therapy will be beneficial in children following cardiac arrest. There are however important differences in the etiology, pathophysiology, neuropathology, therapy and outcome of cardiac arrest in children compared to adults.
We need to conduct a pilot study of hypothermia therapy following cardiac arrest at 11 Children's Hospitals to test the feasibility of recruitment and to test the appropriateness of our inclusion/exclusion criteria prior to proceeding to a large multi-centre trial. We chose 11 large children's hospitals with large cardiac arrest populations with a track record of resuscitation research to improve the feasibility of patient recruitment into this pilot study. The pilot data will be used to do a sample size calculation for the larger randomized controlled study. It will also be important to demonstrate enrolment in an important sub-group of patients, those being placed on ECMO post-arrest. Patients randomized to cooling on ECMO will have rapid core cooling via the extracorporeal circuit and this rapid cooling may lead to a more pronounced therapeutic effect.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00754481
|The Hospital for Sick Children|
|Toronto, Ontario, Canada|
|Montreal, Quebec, Canada|
|Starship Children's Hospital|
|Auckland, New Zealand|
|Great Ormond Street Hospital|
|London, United Kingdom|
|Principal Investigator:||Jamie Hutchison, MD||The Hospital for Sick Children|