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

NCT00878644 | Completed Phase 3 Results DMC

• 2 other identifiers: 619U01HL094339
• Study Type: interventional
• Target: 295
• Locations: 2 countries
• Sites: 34

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.

Conditions

Cardiac Arrest

Keywords

Cardiac Arrest; Cardiopulmonary Arrest; Pediatric Cardiac Arrest; VABS; Vineland Adaptive Behavior Survey; POPC/PCPC; hypoxic-ichemic encephalopathy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Survival

  Measured at one-year anniversary of cardiac arrest.

• 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.

• Neuropsychological Scores (for Participants That Survive)

  Measured at Month 12

Study Arms (2)

Therapeutic Hypothermia

EXPERIMENTAL

Participants will receive therapeutic hypothermia after experiencing cardiac arrest.

Procedure: Therapeutic Hypothermia

Therapeutic Normothermia

ACTIVE COMPARATOR

Participants will receive therapeutic normothermia after experiencing cardiac arrest.

Other: Therapeutic Normothermia

Interventions

Therapeutic Hypothermia PROCEDURE

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.

Therapeutic Hypothermia

Therapeutic Normothermia OTHER

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.

Therapeutic Normothermia

Eligibility Criteria

• Age: 48 Hours - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (34)

The Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

University of Arizona at Tucson

Tucson, Arizona, 85724, United States

Location

Loma Linda University Children's Hospital

Loma Linda, California, 92354, United States

Location

Children's Hospital of Los Angeles

Los Angeles, California, 90028, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Children's Hospital of Denver/University of Colorado

Denver, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Hospital of Atlanta/Emory University

Atlanta, Georgia, 30306, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins Children's Center

Baltimore, Maryland, 21287, United States

Location

University of Michigan, Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Children's Hospital and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Children's Hospital of New York - Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Duke Children's Hospital

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies and Children

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital in Columbus

Columbus, Ohio, 43205, United States

Location

Penn State Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

Children's Hospital of Philidelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

Location

LeBonheur Children's Hospital - University of Tennessee at Memphis

Memphis, Tennessee, 38105, United States

Location

Children's Medical Center Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Sciences Center of San Antonio

San Antonio, Texas, 78229, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113, United States

Location

Seatlle Children's Hospital

Seattle, Washington, 98105, United States

Location

Medical College of Wisconsin/Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (14)

• 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. Multicenter cohort study of in-hospital pediatric cardiac arrest. Pediatr Crit Care Med. 2009 Sep;10(5):544-53. doi: 10.1097/PCC.0b013e3181a7045c.

  PMID: 19451846 RESULT

• 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 Network. In-hospital versus out-of-hospital pediatric cardiac arrest: a multicenter cohort study. Crit Care Med. 2009 Jul;37(7):2259-67. doi: 10.1097/CCM.0b013e3181a00a6a.

  PMID: 19455024 RESULT

• 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. Multicenter cohort study of out-of-hospital pediatric cardiac arrest. Crit Care Med. 2011 Jan;39(1):141-9. doi: 10.1097/CCM.0b013e3181fa3c17.

  PMID: 20935561 RESULT

• 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-Amanfo G, Goodman DM, Fink EL, McQuillen P, Zimmerman JJ, Thomas NJ, van der Jagt EW, Porter MB, Meyer MT, Harrison R, Pham N, Schwarz AJ, Nowak JE, Alten J, Wheeler DS, Bhalala US, Lidsky K, Lloyd E, Mathur M, Shah S, Wu T, Theodorou AA, Sanders RC Jr, Dean JM; THAPCA Trial Investigators. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Engl J Med. 2015 May 14;372(20):1898-908. doi: 10.1056/NEJMoa1411480. Epub 2015 Apr 25.

  PMID: 25913022 RESULT

• Harhay MO, Blette BS, Granholm A, Moler FW, Zampieri FG, Goligher EC, Gardner MM, Topjian AA, Yehya N. A Bayesian Interpretation of a Pediatric Cardiac Arrest Trial (THAPCA-OH). NEJM Evid. 2023 Jan;2(1):EVIDoa2200196. doi: 10.1056/EVIDoa2200196. Epub 2022 Dec 14.

  PMID: 38320098 DERIVED

• Siddique J. Bayesian (re)-Analyses of Clinical Trial Data. NEJM Evid. 2023 Jan;2(1):EVIDe2200297. doi: 10.1056/EVIDe2200297. Epub 2022 Dec 27.

  PMID: 38320013 DERIVED

• Slomine BS, Silverstein FS, Page K, Holubkov R, Christensen JR, Dean JM, Moler FW; Therapeutic Hypothermia after Pediatric Cardiac Arrest (THAPCA) Trial Investigators. Relationships between three and twelve month outcomes in children enrolled in the therapeutic hypothermia after pediatric cardiac arrest trials. Resuscitation. 2019 Jun;139:329-336. doi: 10.1016/j.resuscitation.2019.03.020. Epub 2019 Mar 26.

  PMID: 30922934 DERIVED

• Moler FW, Silverstein FS, Nadkarni VM, Meert KL, Shah SH, Slomine B, Christensen J, Holubkov R, Page K, Dean JM; THAPCA Trial Investigators. Pediatric out-of-hospital cardiac arrest: Time to goal target temperature and outcomes. Resuscitation. 2019 Feb;135:88-97. doi: 10.1016/j.resuscitation.2018.12.012. Epub 2018 Dec 17.

  PMID: 30572071 DERIVED

• Ichord R, Silverstein FS, Slomine BS, Telford R, Christensen J, Holubkov R, Dean JM, Moler FW; THAPCA Trial Group. Neurologic outcomes in pediatric cardiac arrest survivors enrolled in the THAPCA trials. Neurology. 2018 Jul 10;91(2):e123-e131. doi: 10.1212/WNL.0000000000005773. Epub 2018 Jun 8.

  PMID: 29884735 DERIVED

• Meert K, Telford R, Holubkov R, Slomine BS, Christensen JR, Dean JM, Moler FW; Therapeutic Hypothermia after Paediatric Cardiac Arrest (THAPCA) Trial Investigators. Exploring the safety and efficacy of targeted temperature management amongst infants with out-of-hospital cardiac arrest due to apparent life threatening events. Resuscitation. 2016 Dec;109:40-48. doi: 10.1016/j.resuscitation.2016.09.026. Epub 2016 Oct 11.

  PMID: 27737774 DERIVED

• Slomine BS, Silverstein FS, Christensen JR, Holubkov R, Page K, Dean JM, Moler FW; THAPCA Trial Group. Neurobehavioral Outcomes in Children After Out-of-Hospital Cardiac Arrest. Pediatrics. 2016 Apr;137(4):e20153412. doi: 10.1542/peds.2015-3412. Epub 2016 Mar 3.

  PMID: 26940987 DERIVED

• Holubkov R, Clark AE, Moler FW, Slomine BS, Christensen JR, Silverstein FS, Meert KL, Pollack MM, Dean JM. Efficacy outcome selection in the therapeutic hypothermia after pediatric cardiac arrest trials. Pediatr Crit Care Med. 2015 Jan;16(1):1-10. doi: 10.1097/PCC.0000000000000272.

  PMID: 25268768 DERIVED

• Moler FW, Silverstein FS, Meert KL, Clark AE, Holubkov R, Browning B, Slomine BS, Christensen JR, Dean JM. Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials. Pediatr Crit Care Med. 2013 Sep;14(7):e304-15. doi: 10.1097/PCC.0b013e31828a863a.

  PMID: 23842585 DERIVED

• Pemberton VL, Browning B, Webster A, Dean JM, Moler FW. Therapeutic hypothermia after pediatric cardiac arrest trials: the vanguard phase experience and implications for other trials. Pediatr Crit Care Med. 2013 Jan;14(1):19-26. doi: 10.1097/PCC.0b013e31825b860b.

  PMID: 23295834 DERIVED

MeSH Terms

Conditions

Heart Arrest

Interventions

Hypothermia, Induced

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cryotherapy; Therapeutics

Results Point of Contact

• Title: Marianne Gildea, BSN, MS; Director of THAPCA Trials
• Organization: University of Utah

marianne.gildea@hsc.utah.edu

801-608-4907

Study Officials

• Frank W Moler, MD, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Michael Dean, MD, MBA

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: April 8, 2009
• First Posted: April 9, 2009
• Study Start: September 1, 2009
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: September 29, 2017
• Results First Posted: September 29, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (33)