What is the mechanism of action of this treatment?

Induced hypothermia, a common treatment for cardiac arrest, works by lowering the body temperature to reduce metabolic demand and limit neuronal injury. This is crucial for cardiac arrest patients as it helps preserve brain function by slowing down metabolic processes that can lead to cell death. By decreasing the body's temperature, the oxygen and energy requirements of the brain are reduced, mitigating brain damage and improving neurological outcomes. This timely intervention can significantly impact survival and quality of life for cardiac arrest patients.

What side effects are associated with this type of intervention?

Induced hypothermia, used to reduce metabolic demand and limit neuronal injury in cardiac arrest patients, can have several side effects. Common side effects include shivering, which can increase metabolic demand, electrolyte imbalances such as hypokalemia, and an increased risk of infections like pneumonia. Other potential side effects are arrhythmias, coagulopathies, and skin injuries due to prolonged exposure to cold temperatures. These side effects necessitate careful monitoring and management during and after the cooling process.

What prior FDA approvals exist?

The FDA has approved the use of induced hypothermia, also known as therapeutic hypothermia, for the treatment of cardiac arrest. This treatment involves lowering the body temperature to reduce metabolic demand and limit neuronal injury, thereby improving neurological outcomes in patients who have experienced cardiac arrest. While specific drugs are not typically the focus of this therapy, the process often involves the use of cooling devices and protocols to achieve and maintain the target temperature. This approach has been shown to be beneficial in improving survival rates and neurological function in post-cardiac arrest patients.

What other types of research exist?

Promising novel alternatives to induced hypothermia for cardiac arrest patients include: 1) Neuroprotective pharmacological agents such as xenon gas and erythropoietin, which aim to reduce neuronal injury. 2) Advanced resuscitation techniques like extracorporeal membrane oxygenation (ECMO) that provide circulatory support and oxygenation. 3) Therapeutic hypothermia adjuncts, such as trans-nasal evaporative cooling, which offer targeted brain cooling. These alternatives are currently under investigation and show potential for improving outcomes in cardiac arrest patients.

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Other

Cooling Therapy for Pediatric Cardiac Arrest (ICECAP Trial)

N/A

Recruiting

Led By William Meurer, MD

Research Sponsored by University of Michigan

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Requires continuous mechanical ventilation through endotracheal tube or tracheostomy

Age 2 days to < 18 years with corrected gestational age of at least 38 weeks

Must not have

Pre-existing cryoglobulinemia

Active and refractory severe bleeding prior to randomization

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline and 12 months after cardiac arrest

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Therapeutic hypothermia can cause shivering, increased risk of infection due to lowered immune response, changes in heart rhythm, electrolyte imbalances like low potassium or magnesium levels, and potential clotting issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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I was enrolled in the study within 6 hours after my heart started beating on its own again.

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I was in a coma or had severe brain dysfunction after being revived from a cardiac arrest outside the hospital.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have been diagnosed with cryoglobulinemia before.

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I am currently experiencing severe, uncontrollable bleeding.

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I am on high-dose epinephrine or norepinephrine, or I am receiving ECMO.

Select...

I have severe brain development issues or worsening brain disease.

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I had a cardiac arrest due to an injury to my head, chest, or abdomen.

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I have sickle cell anemia.

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I have severe burns or skin issues that prevent cooling treatments.

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I underwent CPR for more than 60 minutes.

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I am currently receiving chemotherapy for a brain tumor.

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I have long-term low body temperature.

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I do not speak English or Spanish.

Select...

I developed diabetes insipidus after a cardiac arrest.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 months after cardiac arrest

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 months after cardiac arrest

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 months after cardiac arrest for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Vineland Adaptive Behavior Scales - Third Edition (VABS-3) Mortality Composite Score at 12 months after return of spontaneous circulation

Secondary study objectives

Change in Pediatric Cerebral Performance Category (PCPC) at 12 months from baseline

Pediatric Resuscitation after Cardiac Arrest (PRCA) at 12 months

Side effects data

From 2014 Phase 3 trial • 295 Patients • NCT00878644

17%

Hypotension

15%

Hypoxic encephalopathy

14%

Hypokalemia

14%

Diabetes insipidus

13%

Anemia

13%

Hypertension

12%

Atelectasis

12%

Hyperglycemia

12%

Seizures

11%

Cerebral edema

10%

Seizure

10%

Anoxic brain damage

Hypoglycemia

Sputum culture positive

Hypernatremia

Hypocalcemia

Pleural effusion

Fever

Hyponatremia

Coagulopathy

Oxygen saturation decreased

Cardiac arrest

Urine output decreased

Pancreatitis

Hyperkalemia

Tachycardia

Blood culture positive

Hypomagnesemia

Hypophosphatemia

Pulmonary edema

Leukocytosis

Rhinovirus infection

Thalamic syndrome

Respiratory infection

Bradycardia

Shivering

Urine culture positive

Lactate dehydrogenase increased

Pneumomediastinum

Pneumothorax

Agitation

Brain herniation

Potassium decreased

Ischemia

Urine output increased

Tachypnea

Hypoxic brain damage

AST increased

Low blood pressure

Hypothermia

Abnormal EEG

Edema

EEG abnormal

Haemoglobin low

Hyperchloremia

Respiratory distress

Skin breakdown

Ventricular tachycardia

Fluid overload

Metabolic acidosis

Anasarca

Escherichia urinary tract infection

Base excess decreased

PO2 decreased

Troponin increased

Bacterial tracheitis

Hypoxemia

Retinal hemorrhage

Diarrhea

Emesis

Pneumonia

Sinusitis

LDH increased

Dysautonomia

Status epilepticus

Posturing

Cardiac failure

Acidosis

Cerebral salt-wasting syndrome

Anisocoria

Pharyngeal edema

Hyperthermia

Asthma

Hypercarbia

Arterial blood pH decreased

Loss of gag reflex

Sinus tachycardia

Adrenal insufficiency

Ischemia cerebral

Dilatation pupillary

Premature ventricular contractions

Acute renal failure

Decreased hemoglobin

Decreased ventricular afterload

Hematocrit low

Hemoglobin decreased

INR decreased

PT increased

WBC increased

Hypochloremia

Hypoproteinemia

Cerebral ischemia

Clonus

Coughing

Diaphragmatic hernia

Emphysema

Unspecified disease of respiratory system

Wheezing

Poor peripheral perfusion

Sepsis

Septic shock

Distended abdomen

Edema of extremities

Edema of lower extremities

Extravasation

Face oedema

DIC

Pneumatosis intestinalis

Multi-organ failure

Candida albicans infection

Respiratory syncytial virus infection

Tracheitis

Myocardial depression

Stools watery

Swallowing disorder

Multi-organ disorder

Hepatomegaly

Hyperbilirubinemia

Liver failure

Escherichia coli infection

Gram-positive cocci infection

Pseudomonas aeruginosa infection NOS

Serous otitis media (glue ear)

Staphylococcus aureus pneumonia

Streptococcus viridans group infection

Urinary tract infection bacterial

Urine candida

Bloody airway discharge

Collapse of lung

Renal injury

Rib fracture

Spinal epidural hematoma

Tibia fracture

APTT decreased

Aspartate aminotransferase increased

B-type natriuretic peptide

BUN increased

CPK increase

CRP increased

PCO2 increased

Sodium low

Transaminitis

GI bleed

Polyuria

Renal function aggravated

Aspiration

Red man syndrome

Hemodynamic instability

Shock vascular

Generalized edema

Bacteria blood identified

Encephalopathy

Hematocrit decreased

Cerebral infarction

Respiratory insufficiency

Hypertonia

Oliguria

Memory deficit

Renal failure

Hypercapnia

Shock

Jugular vein thrombosis

Phlebitis

DVT

HIE

CO2 total abnormal

Glucose increased

Glucose urine present

Atrial tachycardia

Heart rate increased

Bowel ischemia

Gastroesophageal reflux

ARDS

Staphylococcal infection

Chloride low

Creatinine increased

Leukopenia

Hypoalbuminemia

Blood osmolarity increased

Blood pH abnormal

Blood phosphorus increased

IIIrd nerve palsy

Ischemic stroke

Gastrointestinal mucosal sloughing

Gum erosion

Pancreatitis aggravated

Pneumoperitoneum

Saliva secretion excessive

Vomiting

Ionized calcium decreased

Swelling of legs

Acute liver injury

Bilateral pneumonia

Hypoxia

Catheter site infection

Central line infection

Pulmonary edema recurrent

Pulmonary hypertension

Pulmonary vascular disorder

Respiratory acidosis

Respiratory tract infection bacterial

Septicemia

Muscle spasms

Acquired tracheobronchomalacia

Apnea

Aspiration pneumonia

Clotting

Cardiac failure aggravated

Multi organ failure

Pyrexia

Klebsiella pneumonia

Klebsiella pneumoniae infection

Infection pseudomonas aeruginosa

Neurological status deterioration

UTI

Urinary tract infection

Pulmonary hemorrhage

Disseminated intravascular coagulation

Neutropenia

Thrombocytopenia

Subdural hemorrhage

Bundle branch block

Cardiomegaly

Fibrosis myocardial

Junctional rhythm

Left ventricular dysfunction

Left ventricular systolic dysfunction

Dilated pupils

Fixed dilated pupils

Gaze palsy

Pupillary reaction slow

Ascites

Constipation

Gastrointestinal bleeding

Nausea

Catheter site bleeding

Gallbladder edema

Clostridium difficile infection

Haemophilus influenzae infection

Lung infection

Septicemia due to Escherichia coli (E. coli)

Soft tissue infection

Staphylococcal pneumonia

Femur fracture

Fracture of upper end or unspecified part of radius and ulna, closed

Fractured cervical spine

Humerus fracture

Iatrogenic pneumothorax

Ligament injury

ALT increased

Amylase high

Amylase increased

Blood bicarbonate decreased

Blood bicarbonate low

Blood pressure increased

Creatine phosphokinase increased

Drug level above therapeutic

Elevated liver enzymes

Fecal occult blood

Function pulmonary decreased

Gastric pH decreased

Glucose decreased

Glucose high

INR increased

Increased blood pressure

Lactate increased

Lipase increased

Magnesium decreased

Methicillin-resistant Staphylococcus aureus test positive

Neurological examination abnormal

PCO2 abnormal

PTT prolonged

Phosphorus low

Sodium increased

Alkalosis

Hyperammonemia

Hyperamylasemia

Hyperlipasemia

Hypermagnesemia

Hyperphosphatemia

Metabolic alkalosis

Autonomic dysfunction

Autonomic instability

Cerebral hematoma

Increased intracranial pressure

Myoclonic seizure NOS

Myoclonus

Shaking

Tremor

Anuria

Interstitial lung disease

Labored breathing

Rash

Aortic thrombosis

Blood pressure fluctuation

Clot blood

Coldness of lower extremities

DVT of legs

Deep vein thrombosis leg

Thrombosis leg

Band neutrophil count increased

Lung injury

Multiple organ failure

Anoxic encephalopathy

Intracranial hemorrhage

Respiratory failure

Respiratory failure aggravated

Skin ulcer

PVC's

Retinopathy hemorrhagic

Bacterial infection due to staphylococcus aureus

Enterovirus infection

Ventilator associated pneumonia

Yeast infection

Acidosis metabolic

Feeding difficulties and mismanagement

Azotemia

Urinary retention

Breathing abnormally shallow

Bronchial wall thickening

Chronic respiratory failure

Respiratory alkalosis

Wheezing aggravated

Blisters

Diaper rash

Redness

Subcutaneous emphysema

Ulcer skin

Acute hypotension

Venous thrombosis

Platelet count increased

Swelling of limb

Lactate high

Urine ketone body present

Carbon monoxide poisoning

Infusion site erythema

Hypotonia

Potassium increased

Hypercholesterolemia

Cerebral infarct

Hypotensive

100%

80%

60%

40%

20%

Study treatment Arm

Therapeutic Normothermia

Therapeutic Hypothermia

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

10Treatment groups

Experimental Treatment

Group I: Cooling 96 hoursExperimental Treatment1 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 hoursExperimental Treatment1 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 hoursExperimental Treatment1 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 hoursExperimental Treatment1 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 hoursExperimental Treatment1 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 hoursExperimental Treatment1 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 hoursExperimental Treatment1 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 hoursExperimental Treatment1 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 hoursExperimental Treatment1 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 hoursExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Therapeutic Hypothermia

2013

Completed Phase 3

~990

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Induced hypothermia, a common treatment for cardiac arrest, works by lowering the body temperature to reduce metabolic demand and limit neuronal injury. This is crucial for cardiac arrest patients as it helps preserve brain function by slowing down metabolic processes that can lead to cell death. By decreasing the body's temperature, the oxygen and energy requirements of the brain are reduced, mitigating brain damage and improving neurological outcomes. This timely intervention can significantly impact survival and quality of life for cardiac arrest patients.