Therapeutic Hypothermia for Cardiac Arrest

(ICECAP Trial)

Recruiting at 61 trial locations

Overseen By Nia Bozeman

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Disqualifiers: Neurological disability, Terminal illness, Sepsis, 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: 6 to 72 hours

1800 Participants Needed

Trial Summary

What is the purpose of this trial?

A multicenter, randomized, adaptive allocation clinical trial to determine if increasing durations of induced hypothermia are associated with an increasing rate of good neurological outcomes and to identify the optimal duration of induced hypothermia for neuroprotection in comatose survivors of cardiac arrest.

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

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Therapeutic Hypothermia for Cardiac Arrest?

Therapeutic hypothermia has been shown to improve survival and neurological outcomes in patients who survive cardiac arrest. Studies indicate that faster cooling leads to better outcomes, and implementing a targeted temperature protocol can help achieve this. Additionally, therapeutic hypothermia is part of current guidelines for post-resuscitation care, highlighting its importance in improving patient recovery. ^{1 2 3 4 5}

Is therapeutic hypothermia generally safe for humans?

Therapeutic hypothermia can have side effects, including issues with the heart, fluid balance, and infections, and it requires careful monitoring and management. These side effects are seen in various conditions, including cardiac arrest and severe brain injury, and more research is needed to fully understand and manage these risks. ^{6 7 8 9 10}

How is the treatment Therapeutic Hypothermia unique for cardiac arrest?

Therapeutic Hypothermia is unique because it involves cooling the body to a target temperature of 32-34°C to improve survival and brain function after cardiac arrest, unlike other treatments that do not focus on temperature management. It is one of the few advancements that has shown to improve outcomes in cardiac arrest patients, especially when started early after resuscitation. ^{1 2 11 12 13}

Research Team

William Meurer

Principal Investigator

University of Michigan

Robert Silbergleit

Principal Investigator

University of Michigan

Romer Geocadin

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults who've been in a coma after being resuscitated from a cardiac arrest outside of the hospital. They must be cooled to below 34 degrees Celsius within 4 hours of the event, with plans to maintain life support for at least 96 hours. It's not for those unstable after resuscitation, with pre-existing severe neurological issues or terminal illnesses, planned early life support withdrawal, sepsis-related arrests, or prisoners.

Inclusion Criteria

I am 18 years old or older.

Informed consent from legal authorized representative (LAR) including intent to maintain life support for 96 hours

I joined the study within 6 hours of starting cooling treatment.

Exclusion Criteria

Prisoner

My blood pressure and heart rate are stable.

You have plans to stop life support soon.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive varying durations of induced hypothermia to determine optimal neuroprotection

6 to 72 hours

Continuous monitoring during hospital stay

Rewarming

Controlled rewarming to a temperature of 36.5°C over a period equal to the cooling duration

6 to 72 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Periodic assessments, including neurological and cognitive evaluations

Treatment Details

Interventions

• Therapeutic Hypothermia

Trial Overview The study is testing whether longer periods of induced hypothermia (cooling the body) can improve brain function outcomes in patients who have survived cardiac arrest but are comatose. The goal is to find out how long cooling should last to best protect the brain.

Participant Groups

Group I: 72 hours - shockable Experimental Treatment 1 Intervention

Participants with shockable initial rhythm will be assigned to receive 72 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group II: 72 hours - non-shockable Experimental Treatment 1 Intervention

Participants with non-shockable initial rhythm will be assigned to receive 72 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group III: 60 hours - shockable Experimental Treatment 1 Intervention

Participants with shockable initial rhythm will be assigned to receive 60 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group IV: 60 hours - non-shockable Experimental Treatment 1 Intervention

Participants with non-shockable initial rhythm will be assigned to receive 60 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group V: 6 hours - shockable Experimental Treatment 1 Intervention

Participants with shockable initial rhythm will be assigned to receive 6 hours of hypothermia with a target of 33 degrees followed by 6 hours of controlled rewarming.

Group VI: 6 hours - non shockable Experimental Treatment 1 Intervention

Participants with non-shockable initial rhythm will be assigned to receive 6 hours of hypothermia with a target of 33 degrees followed by 6 hours of controlled rewarming.

Group VII: 48 hours - shockable Experimental Treatment 1 Intervention

Participants with shockable initial rhythm will be assigned to receive 48 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group VIII: 48 hours - non-shockable Experimental Treatment 1 Intervention

Participants with non-shockable initial rhythm will be assigned to receive 48 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group IX: 42 hours - non-shockable Experimental Treatment 1 Intervention

Participants with non-shockable initial rhythm will be assigned to receive 42 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group X: 42 Hours - shockable Experimental Treatment 1 Intervention

Participants with shockable initial rhythm will be assigned to receive 42 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group XI: 36 hours - shockable Experimental Treatment 1 Intervention

Participants with shockable initial rhythm will be assigned to receive 36 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group XII: 36 hours - non-shockable Experimental Treatment 1 Intervention

Participants with non-shockable initial rhythm will be assigned to receive 36 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group XIII: 30 hours - shockable Experimental Treatment 1 Intervention

Participants with shockable initial rhythm will be assigned to receive 30 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group XIV: 30 hours - non-shockable Experimental Treatment 1 Intervention

Participants with non-shockable initial rhythm will be assigned to receive 30 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group XV: 24 hours - shockable Experimental Treatment 1 Intervention

Participants with shockable initial rhythm will be assigned to receive 24 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group XVI: 24 hour - non-shockable Experimental Treatment 1 Intervention

Participants with non-shockable initial rhythm will be assigned to receive 24 hours of hypothermia with a target of 33 degrees followed by 24 hours of controlled rewarming.

Group XVII: 18 hours - shockable Experimental Treatment 1 Intervention

Participants with shockable initial rhythm will be assigned to receive 18 hours of hypothermia with a target of 33 degrees followed by 18 hours of controlled rewarming.

Group XVIII: 18 hours - non-shockable Experimental Treatment 1 Intervention

Participants with non-shockable initial rhythm will be assigned to receive 18 hours of hypothermia with a target of 33 degrees followed by 18 hours of controlled rewarming.

Group XIX: 12 hours - shockable Experimental Treatment 1 Intervention

Participants with shockable initial rhythm will be assigned to receive 12 hours of hypothermia with a target of 33 degrees followed by 12 hours of controlled rewarming.

Group XX: 12 hours - non-shockable Experimental Treatment 1 Intervention

Participants with non-shockable initial rhythm will be assigned to receive 12 hours of hypothermia with a target of 33 degrees followed by 12 hours of controlled rewarming.

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 Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Findings from Research

Therapeutic hypothermia significantly improves survival and neurological outcomes in patients who are comatose after cardiac arrest, making it a crucial part of post-resuscitation care.

Controlled feedback systems for inducing and maintaining hypothermia are more effective than prehospital cooling techniques, as they allow for precise temperature management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prehospital cardiac arrest. Therapeutic hypothermia in adults]. Arntz, HR.[2021]

Mild therapeutic hypothermia, applied immediately after restoring circulation in comatose cardiac arrest survivors, improves neurological outcomes, with 1 additional patient achieving intact neurological function for every 6 treated.

Current research is exploring how hypothermia affects drug metabolism and the best combinations of anesthetics and sedatives, as well as potential new applications for hypothermia in emergency situations like exsanguination cardiac arrest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bakken Lecture: the brain, the heart, and therapeutic hypothermia. Kochanek, PM.[2018]

In a study of 12 patients undergoing therapeutic hypothermia after cardiac arrest, temperature measurements from nasopharyngeal and urinary bladder catheters were found to be highly correlated with blood temperature, which is the reference standard.

The findings suggest that both nasopharyngeal and urinary bladder temperature measurements can be reliably used to monitor temperature during therapeutic hypothermia, ensuring accurate temperature control and minimizing cooling-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between blood, nasopharyngeal and urinary bladder temperature during intravascular cooling for therapeutic hypothermia after cardiac arrest. Knapik, P., Rychlik, W., Duda, D., et al.[2012]

The updated therapeutic hypothermia protocol allowed patients who survived cardiac arrest to reach the target temperature 2 hours faster than historical cases, with a median cooling time of 179 minutes compared to 285 minutes.

The use of paralytic agents in the updated protocol was found to safely accelerate cooling, and resulted in better outcomes, with 4 out of 6 patients discharged home or to rehabilitation, compared to only 1 patient from historical cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target temperature within 3 hours: community hospital's experience with therapeutic hypothermia. Gessner, P., Dugan, G., Janusek, L.[2012]

Achieving therapeutic hypothermia (TH) within 6 hours after cardiac arrest is linked to a significantly better neurological outcome, with 80% of patients reaching this target temperature showing good outcomes compared to only 24% of those who achieved it later.

The study analyzed 26 patients treated with TH, revealing a statistically significant relationship between the timing of TH and neurological recovery, suggesting that quicker intervention may improve survival and quality of life after cardiac arrest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Earlier Hypothermia Attainment is Associated with Improved Outcomes after Cardiac Arrest. Chiota, NA., Freeman, WD., Barrett, K.[2021]

Therapeutic hypothermia, defined as cooling the body to less than 35 degrees Celsius, shows potential for neuroprotection after severe brain injuries, but its effectiveness outside of cardiac arrest cases remains unproven.

The approach is associated with significant side effects, such as cardiovascular and infectious complications, highlighting the need for improved techniques and more clinical trials before it can be widely recommended for severe traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hazards of therapeutic hypothermia]. Francony, G., Declety, P., Bouzat, P., et al.[2019]

In a study of 765 out-of-hospital cardiac arrest patients treated with therapeutic hypothermia, common adverse events included pneumonia (48%), seizures (24%), and metabolic disorders, with sustained hyperglycemia and seizures linked to higher mortality rates.

While bleeding and sepsis were more frequent after invasive procedures, they did not correlate with increased mortality, suggesting that not all adverse events during critical care significantly impact patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and their relation to mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. Nielsen, N., Sunde, K., Hovdenes, J., et al.[2010]

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]

Therapeutic hypothermia is effective in reducing cerebral injury and improving neurological outcomes in severely asphyxiated term neonates, but it can also lead to significant side effects, particularly affecting the circulatory system, kidneys, and liver.

A case study highlighted that while purpura fulminans in a neonate was not solely caused by hypothermia, the treatment may have exacerbated coagulopathy, suggesting a need for further research on the risks of severe bleeding disorders in asphyxiated neonates undergoing therapeutic hypothermia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Purpura fulminans after therapeutic hypothermia in an asphyxiated neonate with streptococcemia. Fischer, D., Allendorf, A., Buxmann, H., et al.[2014]

Therapeutic hypothermia is effective in improving neurological outcomes for survivors of cardiac arrest, but it requires careful monitoring and management of potential adverse effects.

Understanding how hypothermia affects drug pharmacokinetics and pharmacodynamics is crucial for using medications effectively during cooling treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical pharmacologic aspects of therapeutic hypothermia after cardiac arrest. Arpino, PA., Greer, DM.[2022]

A survey of 518 physicians from 264 ICUs revealed that 56% of respondents did not change their therapeutic temperature management (TTM) practices for cardiac arrest patients after the 2013 trial, which compared targeted temperatures of 33°C and 36°C.

Despite the trial's findings, 78% of physicians still maintained therapeutic hypothermia between 32-34°C for 12-24 hours, indicating a need for better education and updated guidelines to align clinical practices with new evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in cardiac arrest patients' temperature management after the 2013 "TTM" trial: results from an international survey. Deye, N., Vincent, F., Michel, P., et al.[2023]

Targeted temperature management, or therapeutic hypothermia, is an effective treatment to prevent brain complications after cardiac arrest, as demonstrated in a case study of a 25-year-old female who underwent successful therapy after a 19-minute resuscitation.

This case highlights the potential of therapeutic hypothermia in clinical settings, particularly following cardiac arrest induced by sedation, although comprehensive studies on its efficacy are still lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Therapeutic Hypothermia in a Propofol-Related Cardiac Arrest Case: A Case Report and Literature Review. Yildiz, H.[2019]

Endovascular cooling for therapeutic hypothermia after cardiac arrest resulted in better temperature management, including longer time within the target range and less fluctuation, compared to surface cooling, based on a study of 83 patients.

Despite the improved temperature control and fewer complications with endovascular cooling, there were no significant differences in overall outcomes like mortality or neurological recovery between the two techniques, indicating that both methods may be equally effective in terms of patient survival and recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic hypothermia after cardiac arrest: a retrospective comparison of surface and endovascular cooling techniques. Gillies, MA., Pratt, R., Whiteley, C., et al.[2011]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Prehospital cardiac arrest. Therapeutic hypothermia in adults]. [2021]

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

Bakken Lecture: the brain, the heart, and therapeutic hypothermia. [2018]

3. Ireland pubmed.ncbi.nlm.nih.gov

Relationship between blood, nasopharyngeal and urinary bladder temperature during intravascular cooling for therapeutic hypothermia after cardiac arrest. [2012]

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

Target temperature within 3 hours: community hospital's experience with therapeutic hypothermia. [2012]

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

Earlier Hypothermia Attainment is Associated with Improved Outcomes after Cardiac Arrest. [2021]

6. France pubmed.ncbi.nlm.nih.gov

[Hazards of therapeutic hypothermia]. [2019]

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

Adverse events and their relation to mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. [2010]

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

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

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

Purpura fulminans after therapeutic hypothermia in an asphyxiated neonate with streptococcemia. [2014]

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

Practical pharmacologic aspects of therapeutic hypothermia after cardiac arrest. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Changes in cardiac arrest patients' temperature management after the 2013 "TTM" trial: results from an international survey. [2023]

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

Successful Therapeutic Hypothermia in a Propofol-Related Cardiac Arrest Case: A Case Report and Literature Review. [2019]

13. Ireland pubmed.ncbi.nlm.nih.gov

Therapeutic hypothermia after cardiac arrest: a retrospective comparison of surface and endovascular cooling techniques. [2011]