Therapeutic Hypothermia for Neonatal Encephalopathy

(TIME Trial)

Not currently recruiting at 4 trial locations

Overseen By Krisa Van Meurs, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Disqualifiers: Preterm birth, Low birthweight, Anomalies, 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: 72 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether cooling therapy, known as therapeutic hypothermia, can enhance early brain development in newborns with mild brain injury due to low oxygen at birth. Researchers aim to determine if babies receiving this treatment show better neurodevelopmental outcomes at about one year old compared to those who do not. The study will compare two groups: one receiving cooling treatment and one maintained at normal body temperature (normothermia). Full-term babies with specific signs of mild brain injury at birth may be suitable candidates for this trial.

As an unphased study, this trial provides a unique opportunity to contribute to groundbreaking research that could improve future treatments for newborns.

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

The trial information does not specify whether participants need to stop taking their current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that therapeutic hypothermia is safe for neonates?

Research has shown that cooling therapy is generally safe for newborns with brain injuries caused by a lack of oxygen. Studies have found that it can lower the risk of death and serious disability. For instance, a major study discovered that cooling therapy reduced the chances of death or severe disability in these newborns compared to those kept at normal body temperature.

The treatment involves cooling the baby's body to about 33.5°C (92.3°F) for 72 hours, which helps protect the brain from further harm. While risks like changes in heart rate or blood pressure can occur, these are usually monitored closely. Overall, cooling therapy is well-tolerated in newborns with moderate to severe brain injuries. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about therapeutic hypothermia for neonatal encephalopathy because it offers a unique approach to managing moderate-severe hypoxic-ischemic encephalopathy (HIE) in newborns. Unlike the standard care of maintaining normal body temperature, therapeutic hypothermia involves cooling the infant's body to a specific target temperature of 33.5°C for 72 hours using a temperature-regulating blanket. This cooling process is thought to protect the baby's brain by slowing down the metabolism and reducing the risk of brain injury. By offering a new way to potentially minimize brain damage, this method holds promise for improving outcomes in affected newborns.

What evidence suggests that therapeutic hypothermia might be an effective treatment for neonatal encephalopathy?

Research has shown that cooling a newborn's body, known as therapeutic hypothermia, can help treat hypoxic-ischemic encephalopathy (HIE), a condition where a baby's brain receives insufficient oxygen. Studies have found that this treatment can reduce the risk of death or serious disability by 25% in babies with moderate to severe HIE. In this trial, some participants will receive therapeutic hypothermia, a standard treatment for more severe brain injuries in newborns, while others will receive normothermia as a comparator. Although most research focuses on moderate to severe cases, this study examines how therapeutic hypothermia might benefit babies with mild cases. ^{1 3 6 7 8}

Who Is on the Research Team?

Sonia Bonifacio, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

The TIME Study is for newborns with Mild Hypoxic-Ischemic Encephalopathy, born at or after 36 weeks of pregnancy. They must show signs consistent with an acute event around birth and require resuscitation efforts at 10 minutes old. Babies with genetic issues, born before 36 weeks, weighing less than 1800 grams, or having moderate/severe HIE are excluded.

Inclusion Criteria

The baby's heart rate pattern shows signs of distress during labor or delivery.

My baby was born at or after 36 weeks of pregnancy.

My newborn shows signs of distress from birth complications.

Exclusion Criteria

Your body temperature has been lower than 34°C for more than 1 hour before the study starts.

I have a genetic condition affecting my brain development or causing risk of death.

Patients who are less than 36 weeks pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

First 24 hours of life

Treatment

Therapeutic hypothermia or normothermia is applied for 72 hours using a servo-controlled temperature regulating blanket

72 hours

Initial Hospital Stay

Participants are monitored for various health outcomes, including seizures, feeding initiation, and length of hospital stay

Up to 30 days

Follow-up

Neurodevelopmental outcome is assessed at 12-14 months of age using WIDEA-FS and AIMS

12-14 months

Long-term Follow-up

Developmental outcome is tracked at 2 years of age for all enrolled patients

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Normothermia
• Therapeutic Hypothermia

Trial Overview This study tests the effects of cooling therapy (therapeutic hypothermia) versus normal temperature maintenance (normothermia) on brain health in term neonates with mild brain injury due to oxygen deprivation. Outcomes will be measured by neurodevelopmental progress at about one year old.

How Is the Trial Designed?

Group I: Therapeutic Hypothermia Experimental Treatment 1 Intervention

Therapeutic hypothermia will be achieved using a servo-controlled temperature regulating blanket that is approved for use in neonates and is currently used for the treatment of neonates with moderate-severe HIE. The goal target temperature is 33.5°C ± 0.5°C for 72 hours and the subject will then be rewarmed at a rate of 0.5°C per hour to a goal of 36.5°C.

Group II: Normothermia Active Control 1 Intervention

Normothermia will be achieved using a servo-controlled temperature regulating blanket with the temperature goal of 36.5-37.3°C for 72 hours.

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?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Thrasher Research Fund

Collaborator

Trials

135

Recruited

96,600+

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK567714/

Neonatal Therapeutic Hypothermia - StatPearls - NCBI - NIH Therapeutic hypothermia, which lowers the infant's body temperature to reduce brain injury, is considered the standard of care for term neonates ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5953210/

Therapeutic Hypothermia: How Can We Optimize This ... TH is an effective therapy to reduce death or disability at 18 months of age after moderate or severe neonatal HIE (typical RR 0.75, 95% CI 0.68 to 0.83). TH ...

3. link.springer.com link.springer.com/article/10.1007/s44253-025-00081-6

Effectiveness of therapeutic hypothermia for neonatal ... This pooled relative risk showed that therapeutic hypothermia can reduce mortality among hypoxic-ischemic encephalopathy neonates by 18%.The ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1112066

Childhood Outcomes after Hypothermia for Neonatal ... We previously reported beneficial outcomes from treatment with hypothermia for neonatal hypoxic–ischemic encephalopathy at 18 to 22 months of ...

5. publications.aap.org publications.aap.org/pediatrics/article/133/6/1146/76110/Hypothermia-and-Neonatal-Encephalopathy

Hypothermia and Neonatal Encephalopathy | Pediatrics Hypothermia treatment was associated with a reduction in the secondary outcomes of death (RR, 0.66; 95% CI, 0.45–0.97) and death or cerebral ...

6. sccm.org sccm.org/blog/neonatal-therapeutic-hypothermia-for-hypoxic-ischemic-encephalopathy

Neonatal Therapeutic Hypothermia for Hypoxic-ischemic ... The primary outcome of death or moderate-to-severe disability occurred in 35% of the hypothermic group and 29% of the normothermic group. The ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3519960/

Therapeutic Hypothermia for Neonatal Encephalopathy - PMC Major randomized clinical trials in neonatal HIE have demonstrated reduction in death and disability and continued safety and efficacy of neuroprotection in ...

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2818366

Whole-Body Hypothermia vs Targeted Normothermia for ... Whole-body hypothermia initiated within 6 hours after birth and continued for 48 or 72 hours did not improve cerebral MR biomarkers.