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

Cardiac Arrest Clinical Trial

— THAPCA-OH  

Official title:

Therapeutic Hypothermia After Pediatric Cardiac Arrest (Out of Hospital)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00878644
• Other study ID #: 619
• Secondary ID: U01HL094339
• Status: Completed
• Phase: Phase 3
• First received: April 8, 2009
• Last updated: July 31, 2017
• Start date: September 2009
• Est. completion date: June 2014

Study information

• Verified date: July 2017
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest
• Hypothermia

Intervention

Procedure:
• Therapeutic Hypothermia
Participants who are assigned to receive hypothermia will be cooled to a target temperature of 33º C plus or minus 1º C (32 to 34º C). This temperature will be maintained for 48 hours (2 days) and then participants will be warmed to a target temperature of 36.75º C plus or minus 0.75º C (36 to 37.5º C). This temperature will be maintained until 120 hours (5 days) after the cardiac arrest.

Other:
• Therapeutic Normothermia
Participants who are assigned to receive therapeutic normothermia will have their temperature maintained at 36.75º C plus or minus 0.75º C (36° to 37.5º C) for 120 hours (5 days) after the cardiac arrest.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (4)

Meert KL, Donaldson A, Nadkarni V, Tieves KS, Schleien CL, Brilli RJ, Clark RS, Shaffner DH, Levy F, Statler K, Dalton HJ, van der Jagt EW, Hackbarth R, Pretzlaff R, Hernan L, Dean JM, Moler FW; Pediatric Emergency Care Applied Research Network. Multicent — View Citation

Moler FW, Donaldson AE, Meert K, Brilli RJ, Nadkarni V, Shaffner DH, Schleien CL, Clark RS, Dalton HJ, Statler K, Tieves KS, Hackbarth R, Pretzlaff R, van der Jagt EW, Pineda J, Hernan L, Dean JM; Pediatric Emergency Care Applied Research Network. Multice — View Citation

Moler FW, Meert K, Donaldson AE, Nadkarni V, Brilli RJ, Dalton HJ, Clark RS, Shaffner DH, Schleien CL, Statler K, Tieves KS, Hackbarth R, Pretzlaff R, van der Jagt EW, Levy F, Hernan L, Silverstein FS, Dean JM; Pediatric Emergency Care Applied Research Ne — View Citation

Moler FW, Silverstein FS, Holubkov R, Slomine BS, Christensen JR, Nadkarni VM, Meert KL, Clark AE, Browning B, Pemberton VL, Page K, Shankaran S, Hutchison JS, Newth CJ, Bennett KS, Berger JT, Topjian A, Pineda JA, Koch JD, Schleien CL, Dalton HJ, Ofori-A — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival With Good Neurobehavioral Outcome	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.	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.
Secondary	Survival	Survival at one year after cardiac arrest	Measured at one-year anniversary of cardiac arrest.
Secondary	Change in Neurobehavioral Function From Pre-cardiac Arrest to 12 Months Post-cardiac Arrest	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.	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.
Secondary	Neuropsychological Scores (for Participants That Survive)	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.	Measured at Month 12