Cooling Therapy for Pediatric Cardiac Arrest

(ICECAP Trial)

Recruiting at 56 trial locations

Overseen By Frank Moler, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Must not be taking: Epinephrine, Norepinephrine, Chemotherapy, others

Disqualifiers: Severe neurodevelopmental deficits, Terminal illness, Trauma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

900 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a cooling therapy, known as Therapeutic Hypothermia, for children in a coma after cardiac arrest. Researchers aim to determine if cooling the body for different durations aids brain recovery. The treatment lowers the body's temperature to 33°C (91.4°F) for periods ranging from 0 to 96 hours to identify the most effective duration. Children who have received chest compressions for at least two minutes and require a ventilator may qualify. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance recovery outcomes for children.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that therapeutic hypothermia is safe for pediatric cardiac arrest survivors?

Research has shown that therapeutic hypothermia, which involves cooling the body to a lower temperature, has been safely used in children who survive cardiac arrest. Studies have cooled children to 33°C (about 91°F), and this method was generally well-tolerated. For example, one study examined cooling for different durations—24, 48, and 72 hours—and found that children managed these periods without major side effects.

Some studies found that cooling to 33°C was not more effective than maintaining a normal body temperature (around 98°F) for survival and brain health, but the safety of the cooling process itself was not a major concern. In another study, children who were cooled did not experience more serious problems than those who were not cooled.

Overall, current research considers therapeutic hypothermia a safe treatment option for children after cardiac arrest. However, discussing any concerns with healthcare professionals before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores different durations of therapeutic hypothermia for treating pediatric cardiac arrest, a method that could enhance recovery outcomes compared to traditional treatments. Standard care often focuses on stabilizing body functions, but this trial investigates cooling patients to 33°C for varying periods, potentially reducing brain injury by slowing metabolic processes. By systematically extending cooling durations, the trial aims to identify the optimal balance between cooling time and recovery, offering insights that could refine and improve current treatment protocols for young patients.

What evidence suggests that this trial's treatments could be effective for pediatric cardiac arrest?

Studies have shown that cooling the body, known as therapeutic hypothermia, can improve survival rates after cardiac arrest. For children, maintaining a body temperature of 33°C (about 91.4°F) for a specific duration may protect the brain and aid recovery. This trial will explore various cooling durations, from 0 to 96 hours, to determine the most effective period. Research suggests that cooling for 24 to 72 hours can be effective, with some studies showing higher survival rates compared to maintaining normal body temperature. However, not all studies agree on the optimal cooling duration or the exact benefits. This trial aims to determine if longer cooling periods lead to better recovery for children after cardiac arrest. ^{2 3 4 6 7}

Who Is on the Research Team?

Frank Moler, MD

Principal Investigator

University of Michigan

Alex Topjian, MD

Principal Investigator

Children's Hospital of Philadelphia

William Meurer, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

The P-ICECAP trial is for children aged 2 days to under 18 years who have survived a cardiac arrest but are in a coma. They must be on mechanical ventilation, have been resuscitated within the past 6 hours, and their legal guardians must agree to life support for at least 120 hours. Children with severe heart instability, certain pre-existing conditions, or those who do not speak English or Spanish are excluded.

Inclusion Criteria

Definitive temperature control device initiated

I need a machine to help me breathe through a tube.

I am under 18 years old, born at or after 38 weeks of pregnancy.

Exclusion Criteria

I have been diagnosed with cryoglobulinemia before.

I am currently experiencing severe, uncontrollable bleeding.

Prisoner

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo induced hypothermia at varying durations for neuroprotection

5 days

In-hospital monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular assessments

What Are the Treatments Tested in This Trial?

Interventions

• Therapeutic Hypothermia

Trial Overview

This study tests how effective cooling the body (therapeutic hypothermia) is for protecting the brain after cardiac arrest in kids. It looks at whether cooling longer improves recovery. Kids will be randomly assigned different cooling durations to find out which works best.

How Is the Trial Designed?

Group I: Cooling 96 hours Experimental Treatment 1 Intervention

The participant will be cooled to 33°C for 96 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Group II: Cooling 84 hours Experimental Treatment 1 Intervention

The participant will be cooled to 33°C for 84 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Group III: Cooling 72 hours Experimental Treatment 1 Intervention

The participant will be cooled to 33°C for 72 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Group IV: Cooling 60 hours Experimental Treatment 1 Intervention

The participant will be cooled to 33°C for 60 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Group V: Cooling 48 hours Experimental Treatment 1 Intervention

The participant will be cooled to 33°C for 48 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Group VI: Cooling 36 hours Experimental Treatment 1 Intervention

The participant will be cooled to 33°C for 36 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Group VII: Cooling 24 hours Experimental Treatment 1 Intervention

The participant will be cooled to 33°C for 24 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Group VIII: Cooling 18 hours Experimental Treatment 1 Intervention

The participant will be cooled to 33°C for 18 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Group IX: Cooling 12 hours Experimental Treatment 1 Intervention

The participant will be cooled to 33°Celsius (C) for 12 hours, slowly rewarmed over approximately 16 hours, and then will be kept at a normal temperature (36.8°C or 98.6°F) until the end of the 5th day.

Group X: Cooling 0 hours Experimental Treatment 1 Intervention

Participants will be kept at a normal temperature for the whole 5 days.

Therapeutic Hypothermia is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Therapeutic Hypothermia for:

• Cardiac arrest in adults and children
• Birth asphyxia in newborns

Approved in European Union as Therapeutic Hypothermia for:

• Cardiac arrest in adults and children
• Birth asphyxia in newborns

Approved in Canada as Therapeutic Hypothermia for:

• Cardiac arrest in adults and children
• Birth asphyxia in newborns

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Kennedy Krieger Institute, Baltimore, MD

Collaborator

Trials

2

Recruited

980+

Published Research Related to This Trial

Therapeutic hypothermia is being investigated as a neuroprotective treatment for children with brain injuries, particularly after cardiac arrest, and is already known to improve outcomes in adults and neonates.

In our pediatric ICU, we implement a hypothermia protocol that targets a body temperature of 32-34 degrees Celsius using cooling blankets and iced saline for 24-72 hours, followed by careful re-warming.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I cool children in neurocritical care. Fink, EL., Kochanek, PM., Clark, RS., et al.[2021]

The Therapeutic Hypothermia after Pediatric Cardiac Arrest trials, which took over a decade to plan and implement, aim to evaluate the effectiveness of therapeutic hypothermia in children aged 48 hours to 18 years who have experienced cardiac arrest.

The trials are supported by multiple funding sources and clinical research networks, highlighting the collaborative effort required to conduct large-scale clinical research in pediatric critical care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials. Moler, FW., Silverstein, FS., Meert, KL., et al.[2022]

In a study of 181 pediatric patients who experienced cardiac arrest, therapeutic hypothermia was found to be feasible, with target temperatures achieved within 7 hours, and 78% of survivors discharged home, indicating potential benefits for recovery.

However, the study revealed that a temperature below the target range during treatment was linked to higher mortality rates, highlighting the need for careful temperature management in therapeutic hypothermia protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A tertiary care center's experience with therapeutic hypothermia after pediatric cardiac arrest. Fink, EL., Clark, RS., Kochanek, PM., et al.[2021]

A standardized surface cooling protocol effectively induced and maintained therapeutic hypothermia in 12 pediatric cardiac arrest survivors, achieving the target temperature of 32°C-34°C in 78% of measurements.

While common side effects like hypokalemia and bradycardia were observed, there were no serious adverse events, and 50% of the patients survived to discharge, indicating the protocol's feasibility and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction and maintenance of therapeutic hypothermia after pediatric cardiac arrest: efficacy of a surface cooling protocol. Topjian, A., Hutchins, L., DiLiberto, MA., et al.[2021]

Survival rates after pediatric cardiac arrest are low, ranging from 0% to 38%, with many survivors experiencing neurological injuries, highlighting the need for effective interventions.

The use of mild induced hypothermia has not been conclusively shown to improve outcomes, partly due to uncertainties about optimal cooling protocols and patient selection; the review provides guidelines for its application in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypothermia and pediatric cardiac arrest. Schlunt, ML., Wang, L.[2021]

In a study simulating the infusion of cold intravenous fluids (IVF) to induce therapeutic hypothermia in pediatric patients, the temperature of the fluid entering the patient was significantly higher than the temperature of the fluid in the bag, indicating that infusion rates affect the cooling effect.

For smaller patients (10 kg), the temperature difference (ΔT) was greater, suggesting that faster infusion rates may be less effective in achieving the desired hypothermic temperatures, highlighting the need for alternative techniques when using cold IVF in young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can a Cold (4°C) IV Fluid Bolus to Induce Therapeutic Hypothermia Really Deliver 4°C to Children? Topjian, A., Hamid, M., Hutchins, L., et al.[2016]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9759918/

Target Temperature Management Following Pediatric Cardiac ...

We aimed to compare the efficacy of therapeutic hypothermia for 24, 48, and 72 h, and normothermia following pediatric cardiac arrest.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8037776/

Efficacy of Targeted Temperature Management after Pediatric ...

The use of TTM was associated with a higher survival to hospital discharge; however, it did not significantly increase the annual survival.

3.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1610493

Therapeutic Hypothermia after In-Hospital Cardiac Arrest ...

We now report the results of the THAPCA-IH trial, in which we compared the efficacy of therapeutic hypothermia (target temperature, 33.0°C) with ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00878644

Therapeutic Hypothermia to Improve Survival After Cardiac ...

Participants receiving therapeutic normothermia will have their normal temperature maintained between 36 to 37.5° C for 5 days after the cardiac arrest. Special ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0300957218308876

Therapeutic hypothermia after paediatric cardiac arrest

One-year survival did not differ significantly between hypothermia and normothermia groups (44% [138/317] and 38% [113/ 297], respectively; ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5123789/

Targeted Temperature Management After Pediatric Cardiac ...

Hypothermia (TTM-33°C) was not superior to normothermia (TTM-36.8°C) for survival with good neurological outcome or mortality (7). Newly published 2015 ...

7.

resuscitationjournal.com

resuscitationjournal.com/article/S0300-9572(15)00157-4/abstract

Evolution, safety and efficacy of targeted temperature ...

The aim of this study was to assess the evolution, safety and efficacy of TTM (32–34°C) compared to standard temperature management (STM) (<38°C).