Cardiac ArrestPhase 3THAPCA-OHNCT00878644
Therapeutic Hypothermia to Improve Survival After Cardiac Arrest in Pediatric Patients-THAPCA-OH [Out of Hospital] Trial
A Phase 3 study testing Therapeutic Hypothermia and Therapeutic Normothermia in people with Cardiac Arrest, run by University of Michigan at 34 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 48 hours to 18 years
- Conditions the study is for
- Cardiac Arrest
- What is being tested?
- Therapeutic Hypothermia and Therapeutic Normothermia
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 295 participants
- Where
- 34 sitesin 2 countries
- Study dates
- Sep 2009to Jun 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 48 hours to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 20Show fewer
- 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.
Trial locations and contacts
34 sites in 2 countries.
34 sites in 2 countries
United States33 sites
University of Michigan, Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Hospital of Atlanta/Emory University
Atlanta, Georgia, 30306
Johns Hopkins Children's Center
Baltimore, Maryland, 21287
The Children's Hospital of Alabama
Birmingham, Alabama, 35233
Children's Memorial Hospital
Chicago, Illinois, 60614
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Rainbow Babies and Children
Cleveland, Ohio, 44106
Nationwide Children's Hospital in Columbus
Columbus, Ohio, 43205
Children's Medical Center Dallas
Dallas, Texas, 75235
Children's Hospital of Denver/University of Colorado
Denver, Colorado, 80045
Children's Hospital of Michigan
Detroit, Michigan, 48201
Duke Children's Hospital
Durham, North Carolina, 27710
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
Loma Linda University Children's Hospital
Loma Linda, California, 92354
Children's Hospital of Los Angeles
Los Angeles, California, 90028
University of California Los Angeles
Los Angeles, California, 90095
Kosair Children's Hospital
Louisville, Kentucky, 40202
LeBonheur Children's Hospital - University of Tennessee at Memphis
Memphis, Tennessee, 38105
Medical College of Wisconsin/Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospital and Clinics of Minnesota
Minneapolis, Minnesota, 55404
Children's Hospital of New York - Columbia University Medical Center
New York, New York, 10032
Children's Hospital of Orange County
Orange, California, 92868
Children's Hospital of Philidelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital
Phoenix, Arizona, 85016
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15224
University of Rochester Medical Center
Rochester, New York, 14642
Primary Children's Medical Center
Salt Lake City, Utah, 84113
University of Texas Health Sciences Center of San Antonio
San Antonio, Texas, 78229
University of California San Francisco
San Francisco, California, 94143
Seatlle Children's Hospital
Seattle, Washington, 98105
Washington University in St. Louis
St Louis, Missouri, 63110
University of Arizona at Tucson
Tucson, Arizona, 85724
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Therapeutic Hypothermia After Pediatric Cardiac Arrest (Out of Hospital)
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.
Read the 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.
- Conditions
- Cardiac Arrest
- Being tested
- Therapeutic Hypothermia, Therapeutic Normothermia
- Keywords
- Cardiac Arrest, Cardiopulmonary Arrest, Pediatric Cardiac Arrest, VABS, Vineland Adaptive Behavior Survey, POPC/PCPC, hypoxic-ichemic encephalopathy
- Medical subject headings
- Heart Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Therapeutic HypothermiaProcedure or surgery
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 NormothermiaOther
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 group | Role | What they receive |
|---|---|---|
| Therapeutic Hypothermia | Experimental | Participants will receive therapeutic hypothermia after experiencing cardiac arrest. Receives: Procedure: Therapeutic Hypothermia |
| Therapeutic Normothermia | Active comparator | Participants will receive therapeutic normothermia after experiencing cardiac arrest. Receives: Other: Therapeutic Normothermia |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Survival at one year after cardiac arrest
Measured: Measured at one-year anniversary of cardiac arrest.
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.
Measured: 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)
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: Measured at Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2009 (estimated)
- Study startSep 2009
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Cardiac ArrestStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 295 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Frank W. Moler, M.D, M.S, University of Michigan
- Investigators
- Frank W Moler, MD, MS, Principal investigator, University of MichiganMichael Dean, MD, MBA, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00878644
- Sponsor's protocol ID
- 619
- Other IDs
- U01HL094339
- Acronym
- THAPCA-OH
- Status last verified
- Jul 2017
- First submitted
- 8 Apr 2009
- Last updated
- 29 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 19451846Moler 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.
PubMed 19455024Moler 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.
PubMed 20935561Moler 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.
PubMed 25913022Balcarcel DR, Keim GP, Mehta SD, Harhay MO, Himes BE, van Amsterdam WAC, Moler F, Kirschen MP, Topjian AA, Yehya N. Individualized Treatment Effects of Therapeutic Hypothermia in Children Postcardiac Arrest: A Reanalysis of Two Randomized Clinical Trials. Pediatr Crit Care Med. 2026 Sep 1;27(9):1148-1158. doi: 10.1097/PCC.0000000000004010. Epub 2026 Jul 1.
PubMed 42383826Harhay 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.
PubMed 38320098Siddique J. Bayesian (re)-Analyses of Clinical Trial Data. NEJM Evid. 2023 Jan;2(1):EVIDe2200297. doi: 10.1056/EVIDe2200297. Epub 2022 Dec 27.
PubMed 38320013Slomine 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.
PubMed 30922934Moler 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.
PubMed 30572071Ichord 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.
PubMed 29884735Meert 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.
PubMed 27737774Slomine 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.
PubMed 26940987Holubkov 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.
PubMed 25268768Moler 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.
PubMed 23842585Pemberton 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.
PubMed 23295834
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Hypothermia After Pediatric Cardiac Arrest (Out of Hospital)
- ClinicalTrials.gov ID
- NCT00878644
- Acronym / sponsor ID
- THAPCA-OH / 619
- Conditions
- Cardiac Arrest
- Keywords
- Cardiac Arrest, Cardiopulmonary Arrest, Pediatric Cardiac Arrest, VABS, Vineland Adaptive Behavior Survey, POPC/PCPC, hypoxic-ichemic encephalopathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 295 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Sep 2009
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 9 Apr 2009 (estimated)
- Results
- Posted 29 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Therapeutic Hypothermia | Experimental | Procedure: Therapeutic HypothermiaParticipants will receive therapeutic hypothermia after experiencing cardiac arrest. |
| Therapeutic Normothermia | Active comparator | Other: Therapeutic NormothermiaParticipants will receive therapeutic normothermia after experiencing cardiac arrest. |
Who may qualify
- Ages
- 48 hours to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Therapeutic HypothermiaParticipants 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. | Procedure or surgery | Therapeutic Hypothermia |
| Therapeutic NormothermiaParticipants 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. | Other | Therapeutic Normothermia |
Primary outcome
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.
3 secondary outcomes
Survival
Time frame: Measured at one-year anniversary of 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.
Neuropsychological Scores (for Participants That Survive)
Time frame: Measured at Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19451846Meert 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.
- Results publication: PubMed 19455024Moler 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.
- Results publication: PubMed 20935561Moler 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.
- Results publication: PubMed 25913022Moler 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.
- Derived from this study: PubMed 42383826Balcarcel DR, Keim GP, Mehta SD, Harhay MO, Himes BE, van Amsterdam WAC, Moler F, Kirschen MP, Topjian AA, Yehya N. Individualized Treatment Effects of Therapeutic Hypothermia in Children Postcardiac Arrest: A Reanalysis of Two Randomized Clinical Trials. Pediatr Crit Care Med. 2026 Sep 1;27(9):1148-1158. doi: 10.1097/PCC.0000000000004010. Epub 2026 Jul 1.
- Derived from this study: PubMed 38320098Harhay 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.
- Derived from this study: PubMed 38320013Siddique J. Bayesian (re)-Analyses of Clinical Trial Data. NEJM Evid. 2023 Jan;2(1):EVIDe2200297. doi: 10.1056/EVIDe2200297. Epub 2022 Dec 27.
- Derived from this study: PubMed 30922934Slomine 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.
- Derived from this study: PubMed 30572071Moler 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.
- Derived from this study: PubMed 29884735Ichord 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.
- Derived from this study: PubMed 27737774Meert 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.
- Derived from this study: PubMed 26940987Slomine 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.
- Individual participant dataSharing planned: No
Related trials for Cardiac Arrest
RecruitingObservational study
AI-powered ECG Analysis Using Willem™ Software in High-risk Cardiac Patients (WILLEM)
Cardiomyopathies, Cardiac Arrest
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruitingObservational study
CAROTID DOPPLER AND CEREBRAL OXIMERY IN POST CARDIAC ARREST ICU PATIENTS
Cardiac Arrest (CA), Carotid Doppler
Active, not recruitingPhase 3
The Danish Out-of-Hospital Cardiac Arrest Study
Out-Of-Hospital Cardiac Arrest, Post-Cardiac Arrest Syndrome
RecruitingObservational study
Evaluation of Acid-base Disorders and Ventilation Settings in Cardiogenic Shock and Post-cardiac Arrest Patients: Comparison With VentilO Algorithm
Cardiac Arrest (CA), Cardiogenic Shock
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank W Moler, MD, MS principal investigator
University of Michigan
Michael Dean, MD, MBA principal investigator
University of Utah
34 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Therapeutic Hypothermia and Therapeutic Normothermia in people with Cardiac Arrest, run by University of Michigan at 34 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00878644, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2017.