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

Tracking Information
First Submitted Date ICMJE	April 10, 2009
First Posted Date ICMJE	April 13, 2009
Results First Submitted Date	March 20, 2018
Results First Posted Date	June 15, 2018
Last Update Posted Date	June 15, 2018
Study Start Date ICMJE	September 2009
Actual Primary Completion Date	February 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 15, 2018)	Survival With Good Neurobehavioral Outcome [ Time Frame: 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. Higher values of VABS-II represent a better outcome.
Original Primary Outcome Measures ICMJE; (submitted: April 10, 2009)	Survival With Good Neurobehavioral Outcome [ Time Frame: Measured at Month 12 ]
Change History	Complete list of historical versions of study NCT00880087 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 15, 2018)	Survival [ Time Frame: Measured at one-year anniversary of cardiac arrest. ]Survival at one year after cardiac arrest; Change in Neurobehavioral Function From Pre-cardiac Arrest to 12 Months Post-cardiac Arrest [ Time Frame: 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. Since higher levels of VABS-II represent a better outcome, a larger decline (large negative magnitude of change) in VABS-II score from baseline to one year represents a worse outcome.; Neuropsychological Scores (for Participants Who Survive) [ Time Frame: 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.
Original Secondary Outcome Measures ICMJE; (submitted: April 10, 2009)	Survival [ Time Frame: Measured at Month 12 ]; Change in Neurobehavioral Function From Pre-cardiac Arrest to 12 Months Post-cardiac Arrest [ Time Frame: Measured at Month 12 ]; Neuropsychological Scores (for Participants Who Survive) [ Time Frame: Measured at Month 12 ]; Neurological abnormality scores (for participants who survive) [ Time Frame: Measured at Month 12 ]
Current Other Outcome Measures ICMJE; (submitted: May 15, 2018)	Neurological Abnormality Scores (for Participants Who Survive) [ Time Frame: Measured at Month 12 ]
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Therapeutic Hypothermia to Improve Survival After Cardiac Arrest in Pediatric Patients-THAPCA-IH [In Hospital] Trial
Official Title ICMJE	Therapeutic Hypothermia After Pediatric Cardiac Arrest (In Hospital)
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.
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 cause. 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. 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 in 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 in 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° and 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° and 37.5° C for 5 days after the cardiac arrest. Special temperature control blankets will be placed to maintain their 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.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Cardiac Arrest
Intervention ICMJE	Procedure: Therapeutic Hypothermia 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.; Procedure: 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.
Study Arms	Experimental: Therapeutic Hypothermia Participants will receive therapeutic hypothermia after experiencing cardiac arrest. Intervention: Procedure: Therapeutic Hypothermia; Active Comparator: Therapeutic Normothermia Participants will receive therapeutic normothermia after experiencing cardiac arrest. Intervention: Procedure: Therapeutic Normothermia
Publications *	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.; 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.; 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.; 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.; 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.; 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.; 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.; 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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: May 11, 2016)	329
Original Estimated Enrollment ICMJE; (submitted: April 10, 2009)	500
Actual Study Completion Date	February 2016
Actual Primary Completion Date	February 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: All
Ages	up to 18 Years (Child, Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Canada, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00880087
Other Study ID Numbers ICMJE	620; U01HL094345 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Frank W. Moler, M.D, M.S, University of Michigan
Study Sponsor ICMJE	University of Michigan
Collaborators ICMJE	National Heart, Lung, and Blood Institute (NHLBI)
Investigators ICMJE	Principal Investigator: Frank Moler, MD University of Michigan Principal Investigator: Michael Dean, MD University of Utah
PRS Account	University of Michigan
Verification Date	May 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP