Therapeutic Hypothermia After Pediatric Cardiac Arrest (Out of Hospital) (THAPCA-OH)
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September 2009 - June 2014
February 10, 2017
February 10, 2017
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Commercial Use Data Restrictions No
Data Restrictions Based On Area Of Research No
To evaluate the efficacy of therapeutic hypothermia compared to therapeutic normothermia at increasing 12 month survival rates and decreasing neurologic deficits in infants and children who experience an out-of-hospital cardiac arrest.
Out-of-hospital cardiac arrests are associated with high rates of mortality and disability. Cardiac arrest is a sudden, unexpected loss of heart function that may result in injury to the brain from insufficient blood flow and oxygen. In 2002, clinical trials involving adults reported that therapeutic hypothermia improved neurologic outcomes after out-of-hospital cardiac arrests. International guidelines recommended therapeutic hypothermia for adults with similar clinical presentations to the 2002 trial participants. Conversely, observational studies have not associated therapeutic hypothermia with improved outcomes in children after a cardiac arrest. The THAPCA-OH trial was initiated due to the lack of published results from randomized trials on pediatric populations, and the significant differences that exist regarding cardiac arrest in pediatric and adult populations. The THAPCA-OH trial compared the efficacy of therapeutic hypothermia and therapeutic normothermia in pediatric populations after out-of-hospital cardiac arrests by measuring 12-month survival rates with good neurobehavioral outcomes.
Patients were identified at 38 sites in the United States and Canada who met the inclusion criteria and who had not met the study exclusion. Participants were required to be pediatric patients who experienced a cardiac arrest outside of a hospital that required chest compression for at least 2 minutes with return of circulation (ROSC/ROC) for 20 minutes and required continuous mechanical ventilation after ROC. Pediatric patient population was defined as being greater than 48 hours (correction for gestational age of at least 38 weeks) and less than 18 years of age.
In total, 295 participants underwent randomization at 36 sites. 155 participants were assigned to therapeutic hypothermia and 140 participants were assigned to therapeutic normothermia. 142 assigned to hypothermia and 128 assigned to normothermia had sufficient pre-arrest neurobehavioral function to be eligible for analysis of the primary efficacy endpoint, survival with VABS-II score of at least 70 at one year. At the completion of the study, 138 therapeutic hypothermia-assigned participants and 122 therapeutic normothermia-assigned participants eligible for the primary analysis had one-year VABS-II score data for evaluation of the primary endpoint.
Exclusions included some of the following criteria: Glasgow Coma Scale motor response of 5 or 6, terminal illness, pregnancy, drowning in ice water, contraindicated participation related to CNS, blood, skin, or severe trauma, randomization unattainable within 6 hours of ROSC, continuous infusion of epinephrine or norepinephrine at very high doses (≥2 ug/kg/minute) received immediately prior to randomization.
THAPCA-OH was phase 3 trial and single blind to the outcomes assessor. Eligible patients were randomized in a 1:1 ratio within 6 hours after the return of circulation. Special temperature control blankets were placed to maintain body temperature in the assigned range. Patients assigned to therapeutic normothermia had their temperature maintained at 36.75º C ± 0.75º C for 120 hours after the cardiac arrest. Conversely, patients assigned to therapeutic hypothermia were cooled to the target temperature of 33º C ± 1º C. After maintaining the cooled temperature for 48 hours, patients were warmed to 36.75º C ± 0.75º C over a period of at least 16 hours, which was maintained until 120 hours after the cardiac arrest.
Parents or guardians of participants were instructed to complete the VABS-II Parent/Caregiver Rating Form within 24 hours of randomization, which served as a neurobehavioral pre-CA baseline. Demographic information, medical and functional status, and a measure of family functioning were also recorded by research coordinators. Patients with a VABS-II score ≥ 70 prior to cardiac arrest (or no more than mild dysfunction per both POPC and PCPC if pre-arrest VAS-II was unavailable) were included in the primary outcome assessment, and all patients were included in analysis of secondary outcomes. The primary outcome was survival with a good neurobehavioral outcome at 12 months, defined as an age-corrected standard VABS-II score of 70 or higher on a scale of 20 to 160. Secondary outcomes were survival at 12 months and change in neurobehavioral function.
Prior to discharge, physical and functional assessments were performed by study researchers. At Day 28, vital status was recorded. At months 3 and 12, a trained research assistant, unaware of treatment group assignment, conducted a semi-structured interview by telephone to gather medical information and assess neurobehavioral function (including the VABS-II – Survey Interview Form). At month 12, participants attended an on-site visit for an examination by a neurologist and cognitive testing by a psychologist.
Among the patients who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group. Among all randomized patients, the change in the VABS-II score from baseline to 12 months was not significantly different and 1-year survival was similar between the groups.
In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year.
N Engl J Med. 2015 May 14; 372(20):1898-908.
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