Therapeutic Hypothermia to Improve Survival After Cardiac Arrest in Pediatric Patients-THAPCA-IH [In Hospital] Trial

NCT00880087 | Completed Results DMC

• 2 other identifiers: 620U01HL094345
• Study Type: interventional
• Target: 329
• Locations: 3 countries
• Sites: 33

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 in the hospital.

Conditions

Cardiac Arrest

Keywords

Cardiac Arrest; Cardiopulmonary Arrest; Pediatric Cardiac Arrest; VABS; Vineland Adaptive Behavior Scale; POPC/PCPC; hypoxic-ischemic 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. Higher values of VABS-II represent a better 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 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 Who Survive)

  Measured at Month 12

Other Outcomes (1)

• Neurological Abnormality Scores (for Participants Who 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.

Procedure: Therapeutic Normothermia

Interventions

Therapeutic Hypothermia PROCEDURE

Participants who are assigned to receive therapeutic 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 PROCEDURE

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 (33)

The Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, 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 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

Riley Children's Hospital

Indianapolis, Indiana, 46202, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins Hospital

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

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Duke Children's Hospital

Durham, North Carolina, 27710, 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

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, 84108, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Bristol Royal Hospital for Children

Bristol, BS2 8BJ, United Kingdom

Location

University of Hampton

Hampton, SO16 6YD, United Kingdom

Location

Alder Hey Children's Hospital

Liverpool, L12 2AP, United Kingdom

Location

Evalina Children's at Guys's and St. Thomas' Hospital

London, SE1 7EH, United Kingdom

Location

Great Ormand Street Hospital

London, WC1N 3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

Related Publications (10)

• 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

• 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, 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, Browning B, Pemberton VL, Page K, Gildea MR, Scholefield BR, Shankaran S, Hutchison JS, Berger JT, Ofori-Amanfo G, Newth CJ, Topjian A, Bennett KS, Koch JD, Pham N, Chanani NK, Pineda JA, Harrison R, Dalton HJ, Alten J, Schleien CL, Goodman DM, Zimmerman JJ, Bhalala US, Schwarz AJ, Porter MB, Shah S, Fink EL, McQuillen P, Wu T, Skellett S, Thomas NJ, Nowak JE, Baines PB, Pappachan J, Mathur M, Lloyd E, van der Jagt EW, Dobyns EL, Meyer MT, Sanders RC Jr, Clark AE, Dean JM; THAPCA Trial Investigators. Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children. N Engl J Med. 2017 Jan 26;376(4):318-329. doi: 10.1056/NEJMoa1610493. Epub 2017 Jan 24.

  PMID: 28118559 RESULT

• 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

• 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

• Slomine BS, Silverstein FS, Christensen JR, Holubkov R, Telford R, Dean JM, Moler FW; Therapeutic Hypothermia after Paediatric Cardiac Arrest (THAPCA) Trial Investigators. Neurobehavioural outcomes in children after In-Hospital cardiac arrest. Resuscitation. 2018 Mar;124:80-89. doi: 10.1016/j.resuscitation.2018.01.002. Epub 2018 Jan 3.

  PMID: 29305927 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

Related Links

• IH THAPCA Abstract

MeSH Terms

Conditions

Heart Arrest; Hypoxia-Ischemia, Brain

Interventions

Hypothermia, Induced

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cryotherapy; Therapeutics

Results Point of Contact

• Title: Dr. Rich Holubkov, Professor of Pediatrics
• Organization: University of Utah

richard.holubkov@hsc.utah.edu

807-587-3326

Study Officials

• Frank Moler, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Michael Dean, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• 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 10, 2009
• First Posted: April 13, 2009
• Study Start: September 1, 2009
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: June 15, 2018
• Results First Posted: June 15, 2018

Record last verified: 2018-05

Locations

CA (1); GB (7); US (25)