Hypothermia for Cardiac Arrest in Paediatrics

Hypothermia for Cardiac Arrest in Paediatrics (HypCAP) - Pilot Study

The investigators hypothesized that, following cardiac arrest in pediatric patients, hypothermia therapy will improve the proportion of patients with a good functional outcome compared to a normothermic control group.

Study Overview

• Status: Completed
• Conditions: Cardiac Arrest
• Intervention / Treatment: Other: Normothermia; Other: Hypothermia

Detailed Description

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 completed 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. This protocol was used to develop the protocol for the THAPCA trials (see 2 manuscripts published Moler et al NEJM 2015 and 2017 and multiple other manuscripts). Hypothermia therapy, compared to active maintenance of normothermia, had no beneficial effect on functional outcome or mortality in children with out-of-hospital or in-hospital cardiac arrest.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • The Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada
      • Sainte-Justine Hospital
• New Zealand
  • Auckland, New Zealand
    • Starship Children's Hospital
• United Kingdom
  • London, United Kingdom
    • Great Ormond Street Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent by parent or legal guardian
• Age ≥ 38 weeks gestation up to and including 17 years
• Patient admitted with a diagnosis of a cardiac arrest requiring compressions ≥3 minutes
• Remain comatose i.e. have Glasgow Coma Score less than or equal to 10 assessed at the tertiary level pediatric hospital at least 1 hour post- cardiac arrest
• Invasive mechanical ventilation

Exclusion Criteria:

• Cardiac arrest lasting ≥45 minutes, irregardless of commencement of ECMO
• Refractory hemorrhagic shock
• Dysrhythmia leading to cardiac arrest, where cooling would be part of standard therapy
• Suspected diagnosis of brain death as defined as fixed and dilated pupils, Glasgow Coma Score of 3 and no evidence of brain function on neurological examination
• Patients who have had a prolonged cardiac arrest at the scene of a trauma
• Decision to withhold (DNR) or withdraw life sustaining therapies
• Acute Birth asphyxia
• Terminal illness, not expected to survive 12 months
• Cardiac arrest caused by septic shock
• Severe neurodevelopmental disability or persistent vegetative state prior to cardiac arrest
• Near drowning in ice water and temperature <32ºC on admission to study site
• It has been more than 6 hours following cardiac arrest (estimated by first responder)
• Previous enrolment in the HypCAP Pilot Study
• Pregnant
• Parent/Guardian refuse consent
• Responsible physician refuses to enrol patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1	Other: Normothermia; Patients randomized to the Normothermia arm (esophageal temp 36.5-37.5 ºC) were maintained at an esophageal temperature of 36.5-37.5ºC for 48 hours. Patients who were hypothermic (temperature < 35 ºC) when randomized to the normothermia group were rewarmed slowly using the servo-controlled mattress. Patients who were hyperthermic following randomization to the normothermia group were actively cooled to normothermia using the servo-controlled mattress. Neuromuscular blockers were administered as needed intravenously in both groups of patients to prevent shivering.
EXPERIMENTAL: 2	Other: Hypothermia; Patients randomized to the Hypothermia arm (esophageal temp 33º to 34 °C) were cooled rapidly using the cooling protocol developed for the Hypothermia Paediatric Head Injury Trial. A temperature probe was placed in the esophagus and its position confirmed using a chest radiograph. Patients were 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 reached 34.0ºC, the ice and second cooling blanket was removed and esophageal temperature was maintained at 33º to 34 °C for 48 hours using the servo-controlled cooling mattress. Patients treated with ECMO were cooled using the extracorporeal circuit cooling-device. Rewarming was done at a rate of 0.5 ºC every 2 hours until an esophageal temperature of 36.5 ºC was reached. Thereafter temperature was recorded but not controlled by surface cooling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	Assessed at 12 months post cardiac arrest

Secondary Outcome Measures

Outcome Measure	Time Frame
Cognitive and motor measures	Assessed at 12 months post-arrest
Mortality	Assessed at 1, 3, 6, and 12 months post-arrest
Cerebral edema	12 months
Adverse effects of hypothermia therapy	12 months

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Jamie Hutchison, MD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (ACTUAL): September 1, 2009
• Study Completion (ACTUAL): September 1, 2010

Study Registration Dates

• First Submitted: September 17, 2008
• First Submitted That Met QC Criteria: September 17, 2008
• First Posted (ESTIMATE): September 18, 2008

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2021
• Last Update Submitted That Met QC Criteria: July 8, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Paediatrics
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Body Temperature Changes; Heart Arrest; Hypothermia
• Other Study ID Numbers: 1000004888