Therapeutic Hypothermia to Improve Survival After Cardiac Arrest in Pediatric Patients-THAPCA-OH [Out of Hospital] Trial

Phase 3

Completed

Conditions: Cardiac Arrest

Interventions: Other: Therapeutic Normothermia
Procedure: Therapeutic Hypothermia

Registration Number: NCT00878644

Lead Sponsor: University of Michigan

Brief Summary: Cardiac arrest is a sudden, unexpected loss of heart function. Therapeutic hypothermia, in which the body's temperature is lowered and maintained several degrees below normal for a period of time, has been used to successfully treat adults who have experienced cardiac arrest. This study will evaluate the efficacy of therapeutic hypothermia at increasing survival rates and reducing the risk of brain injury in infants and children who experience a cardiac arrest while out of the hospital.

Detailed Description: Cardiac arrest occurs when the heart suddenly stops beating and blood flow to the body is halted. It can occur while people are in the hospital because of a medical condition, or while people are out of the hospital as a result of an accident or other causes. Cardiac arrest is a serious event that is associated with high rates of death and long-term disability. When a person experiences cardiac arrest, insufficient amount of blood flow and oxygen can result in brain injury.

Therapeutic hypothermia is a therapy that involves a controlled lowering of the body temperature and then maintenance of this lower temperature for a period of time. The treatment may result in reduced brain injury. Therapeutic hypothermia has been successfully used in adults who experience cardiac arrest to improve survival rates and health outcomes, and it has also been studied in newborn infants who have suffered from perinatal asphyxia. The purpose of this study is to evaluate the efficacy of therapeutic hypothermia at improving survival rates and reducing brain injury in infants and children who experience cardiac arrest while out of the hospital.

Study researchers will conduct this study in collaboration with the following two pediatric clinical research networks: the Pediatric Emergency Care Applied Research Network (PECARN), funded by the Emergency Medical Services for Children (EMSC) program, and the National Institute of Child Health and Human Development (NICHD) Collaborative Pediatric Critical Care Research Network (CPCCRN).

The study will enroll infants and children who have suffered a cardiac arrest while out of the hospital. Randomization must occur within 6 hours of return of spontaneous circulation. Participants will be randomly assigned to receive either therapeutic hypothermia or therapeutic normothermia. Participants receiving therapeutic hypothermia will have their body temperature reduced to between 32 to 34° Celsius (C) and will remain at this temperature for 2 days. Their body temperature will then be slowly increased to the normal temperature of 36 to 37.5° C, which will be maintained until 5 days after the cardiac arrest. Participants receiving therapeutic normothermia will have their normal temperature maintained between 36 to 37.5° C for 5 days after the cardiac arrest. Special temperature control blankets will be placed to maintain body temperature in the assigned range. After 5 days, each participant's temperature will be managed by their medical care team.

While participants are in the hospital, they will undergo frequent blood and urine collections, chest x-rays, and temperature measurements; parents of participants will complete questionnaires. When participants are ready to leave the hospital, study researchers will perform a physical and functional assessment. Twenty-eight days after the cardiac arrest, researchers will contact parents of participants to gather information on the participants' health and medical condition. At Months 3 and 12, a child development expert will contact parents to gather medical information. At Month 12, participants will attend a study visit for a neurologic examination and testing with a psychologist trained in rehabilitation.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 295

Inclusion Criteria

Patient suffered cardiac arrest requiring chest compressions for at least 2 minutes (120 seconds) with ROSC/ROC; AND
Age greater than 48 hours (with a corrected gestational age of at least 38 weeks) and less than 18 years; AND
Patient requires continuous mechanical ventilation; AND
The cardiac arrest was unplanned (i.e., not part of cardiac surgical procedure)

Exclusion Criteria

The parent or legal guardian does not speak English or Spanish (the only two languages in which VABS II is standardized)
Randomization is impossible within six hours of ROSC; OR
Patient is on extracorporeal membrane oxygenation (ECMO) when arrest occurs; OR
Continuous infusion of epinephrine or norepinephrine at very high doses (≥2 ug/kg/minute) received immediately prior to randomization; OR Glasgow Coma Scale motor response of five (localizing pain or for infants less than two years, withdraws to touch) or six (obeys commands, or for infants, normal spontaneous movement) prior to randomization; OR
History of a prior cardiac arrest with chest compressions for at least two minutes during the current hospitalization but outside the 6 hour window for randomization; OR
Pre-existing terminal illness with life expectancy < 12 months; OR
Lack of commitment to aggressive intensive care therapies including do not resuscitate orders and other limitations to care; OR
Cardiac arrest was associated with severe brain, thoracic, or abdominal trauma; OR
Active and refractory severe bleeding prior to randomization; OR
Near drowning in ice water with patient core temperature ≤32 °C on presentation; OR
Patient is pregnant; OR
Patient participation in a concurrent interventional trial whose protocol, in the judgment of the THAPCA investigators, prevents effective application of one or both THAPCA therapeutic treatment arms, or otherwise significantly interferes with carrying out the THAPCA protocol; OR
Patient is newborn with acute birth asphyxia; OR

_ Patient cared for in a neonatal intensive care unit (NICU) after arrest (ie, would not be admitted to PICU); OR
Patient has sickle cell anemia; OR
Patient known to have pre-existing cryoglobulinemia; OR
Central nervous system tumor with ongoing chemotherapy or radiation therapy; OR
Chronic hypothermia secondary to hypovolemic, pituitary, or related condition for which body temperature is consistently below 37 °C ; OR progressive degenerative encephalopathy; OR
Any condition in which direct skin surface cooling would be contraindicated, such as large burns, decubitus ulcers, cellulitis, or other conditions with disrupted skin integrity (NOTE: patients with open chest CPR should be included but placement of cooling mattresses will be modified as needed); OR
Previous enrollment in the THAPCA Trials.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Therapeutic Normothermia	Therapeutic Normothermia	Participants will receive therapeutic normothermia after experiencing cardiac arrest.
Therapeutic Hypothermia	Therapeutic Hypothermia	Participants will receive therapeutic hypothermia after experiencing cardiac arrest.

Primary Outcome Measures

Name	Time	Method
Survival With Good Neurobehavioral Outcome	Survival was assessed at one-year anniversary of cardiac arrest; among survivors at this one-year anniversary, the VABS-II valid assessment window ranged from 30 days prior to until 183 days after the one-year anniversary date.	Survival at one-year anniversary of cardiac arrest, with a standardized VABS-II score of 70 or greater per evaluation performed at any time from 30 days prior to until 183 days after the one-year anniversary of cardiac arrest.

Secondary Outcome Measures

Name	Time	Method
Change in Neurobehavioral Function From Pre-cardiac Arrest to 12 Months Post-cardiac Arrest	Survival was assessed at one-year anniversary of cardiac arrest; among survivors at this one-year anniversary, the VABS-II valid assessment window ranged from 30 days prior to until 183 days after the one-year anniversary date.	Change in VABS-II score from baseline to one year, with death at 1 year treated as worst possible outcome, and lowest possible VABS-II score at one year (regardless of baseline VABS-II score) treated as the second worst possible outcome.
Neuropsychological Scores (for Participants That Survive)	Measured at Month 12	Functioning, as assessed by the Mullen Early Learning Composite (for children age \< 5 years 9 months) or by the 2-subset version of the Wechsler Abbreviated Scale of Intelligence (WASI). As these two function measures are scaled in the same fashion, the two age groups are combined.
Survival	Measured at one-year anniversary of cardiac arrest.	Survival at one year after cardiac arrest

Trial Locations

Locations (34): University of California Los Angeles
🇺🇸
Los Angeles, California, United States
Children's Memorial Hospital
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Chicago, Illinois, United States
Children's Hospital and Clinics of Minnesota
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Minneapolis, Minnesota, United States
Cincinnati Children's Hospital
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Cincinnati, Ohio, United States
Nationwide Children's Hospital in Columbus
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Columbus, Ohio, United States
University of Texas Health Sciences Center of San Antonio
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San Antonio, Texas, United States
Seatlle Children's Hospital
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Seattle, Washington, United States
The Children's Hospital of Alabama
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Birmingham, Alabama, United States
Phoenix Children's Hospital
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Phoenix, Arizona, United States
Loma Linda University Children's Hospital
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Loma Linda, California, United States
Children's Hospital of Los Angeles
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Los Angeles, California, United States
University of Arizona at Tucson
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Tucson, Arizona, United States
Children's Hospital of Denver/University of Colorado
🇺🇸
Denver, Colorado, United States
University of California San Francisco
🇺🇸
San Francisco, California, United States
Children's Hospital of Atlanta/Emory University
🇺🇸
Atlanta, Georgia, United States
Kosair Children's Hospital
🇺🇸
Louisville, Kentucky, United States
Johns Hopkins Children's Center
🇺🇸
Baltimore, Maryland, United States
University of Michigan, Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Children's Hospital of Michigan
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Detroit, Michigan, United States
Children's Hospital of New York - Columbia University Medical Center
🇺🇸
New York, New York, United States
Washington University in St. Louis
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Saint Louis, Missouri, United States
Duke Children's Hospital
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Durham, North Carolina, United States
Rainbow Babies and Children
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Cleveland, Ohio, United States
Penn State Children's Hospital
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Hershey, Pennsylvania, United States
Children's Hospital of Philidelphia
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Philadelphia, Pennsylvania, United States
LeBonheur Children's Hospital - University of Tennessee at Memphis
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Memphis, Tennessee, United States
University of Pittsburgh Medical Center
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Pittsburgh, Pennsylvania, United States
Primary Children's Medical Center
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Salt Lake City, Utah, United States
Children's Medical Center Dallas
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Dallas, Texas, United States
The Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
Medical College of Wisconsin/Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
University of Rochester Medical Center
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Rochester, New York, United States
Children's Hospital of Orange County
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Orange, California, United States
Children's National Medical Center
🇺🇸
Washington, D.C., District of Columbia, United States