Cooling Therapy for Pediatric Cardiac Arrest

(ICECAP Trial)

Recruiting at 53 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

Trial Summary

What is the purpose of this trial?

This trial is testing if cooling the body can help protect the brains of children who are in a coma after a heart attack. The researchers believe that keeping the body cool might help more children recover well or improve the recovery of those already doing well.

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 data supports the effectiveness of the treatment Therapeutic Hypothermia for pediatric cardiac arrest?

Therapeutic hypothermia has been shown to improve neurological outcomes in adults after cardiac arrest and in newborns with oxygen deprivation at birth. It is being studied for its potential benefits in children after cardiac arrest, although the best methods and patient selection are still being researched. ^{1 2 3 4 5}

Is cooling therapy safe for children after cardiac arrest?

Research on cooling therapy (also known as therapeutic hypothermia) for children after cardiac arrest has looked at its feasibility and side effects. While the studies focus on its use in emergencies, they do mention monitoring for adverse events, suggesting that safety is a key consideration in its application. ^{1 2 4 5 6}

How is the treatment Therapeutic Hypothermia unique for pediatric cardiac arrest?

Therapeutic Hypothermia is unique because it involves cooling the body to a target temperature of 32-34 degrees Celsius (about 90-93 degrees Fahrenheit) using cooling blankets and intravenous iced saline, aiming to protect the brain after cardiac arrest. This approach is different from other treatments as it focuses on reducing brain injury by lowering body temperature for 24-72 hours, which is not a standard practice for this condition. ^{1 3 4 5 6}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A tertiary care center's experience with therapeutic hypothermia after pediatric cardiac arrest. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

How I cool children in neurocritical care. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Can a Cold (4°C) IV Fluid Bolus to Induce Therapeutic Hypothermia Really Deliver 4°C to Children? [2016]

5. India pubmed.ncbi.nlm.nih.gov

Hypothermia and pediatric cardiac arrest. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Induction and maintenance of therapeutic hypothermia after pediatric cardiac arrest: efficacy of a surface cooling protocol. [2021]