Comparing therapies for infants with mild brain injury

COOLPRIME: Comparative Effectiveness for Cooling Prospectively Infants With Mild Encephalopathy

This study is testing whether cooling therapy can help infants with mild brain injury do better in their development compared to regular body temperature treatment.

Quick facts

• Study type: Observational
• Enrollment: 460 (estimated)
• Ages: 36 Weeks and up
• Sex: All
• Sponsor: University of Texas Southwestern Medical Center (Academic / other)
• Locations: 1 site (Dallas, Texas)
• Trial ID: NCT04621279 on ClinicalTrials.gov

What this trial studies

This observational study aims to evaluate the effectiveness of therapeutic hypothermia (TH) compared to normothermia in improving neurodevelopmental outcomes for infants diagnosed with mild hypoxic ischemic encephalopathy (HIE). Conducted across 15 sites, the study will enroll 460 infants and assess outcomes at 2 years of age. It will also investigate the adverse effects of TH on both the infants and their families, as well as the variability of treatment effects based on physiological biomarkers collected within the first 6 hours after birth. The decision to use TH or normothermia will depend on the clinical practices at each participating site.

Who should consider this trial

Good fit: Ideal candidates are neonates born at or after 35 weeks gestation who exhibit mild encephalopathy and perinatal acidosis within 6 hours of birth.

Not a fit: Patients who do not meet the inclusion criteria, such as those with severe HIE or born before 35 weeks gestation, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved neurodevelopmental outcomes for infants with mild HIE.

How similar studies have performed: Other studies have shown promise in using therapeutic hypothermia for neonatal conditions, but this specific comparative effectiveness approach is relatively novel.

Eligibility criteria

Inclusion Criteria:

Infants must meet all 3 inclusion criteria

1. Neonates born at ≥ 36 0/7 weeks
2. Mild Encephalopathy on neonatal neurologic exam within 6 hours after birth: defined as presence of at least 2 signs of mild, moderate, or severe encephalopathy with no more than 2 signs in the moderate or severe category.
3. Perinatal Acidosis based on at least one of the following (A or B):

   1. pH ≤ 7.00 in any cord or first infant gas (arterial, venous, or capillary) within ≤ 60 min OR base deficit ≥ 16 in any cord or first infant gas (arterial, venous or capillary) within ≤ 60 min
   2. If pH is between 7.01 and 7.15, OR base deficit is between 10 and 15.9 mmol/liter, OR blood gas is not available, an acute perinatal event is an additional criteria required (see below definition)

An acute perinatal event is defined by at least one of the following:

1. Apgar score at 10 min ≤ 5
2. Continued need for resuscitation at 10 min (chest compressions, bag mask ventilation, or positive pressure ventilation)
3. Uterine rupture, placental abruption, cord accident (prolapse, rupture, knot or tight nuchal cord)
4. maternal trauma, maternal hemorrhage, or cardiorespiratory arrest
5. fetal exsanguination from either vasa previa or feto-maternal hemorrhage, shoulder dystocia
6. Any evidence suggestive of acute perinatal event.

Infants are still eligible for enrollment in the COOLPRIME study if the cord or infant's first blood gas (arterial, venous, or capillary) is obtained \>60 minutes of life.

Exclusion Criteria:

1. Gestational age at birth \< 36 0/7 weeks
2. Birth weight \< 1800gm
3. Head circumference \<30cm
4. Congenital or chromosomal anomaly associated with abnormal neurodevelopment or death
5. Moderate or Severe HIE of 3 or more moderate or severe abnormalities on COOLPRIME Sarnat exam within 6 hours of life
6. Any seizures within first six hours of life
7. Redirection of care is being considered

Where this trial is running

Dallas, Texas

• University of Texas Southwestern Medical Center — Dallas, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Lina Chalak, MD — University of Texas Southwestern Medical Center
• Study coordinator: Lina Chalak, MD

Conditions Mild Hypoxic Ischemic Encephalopathy of Newborn; mild HIE; neonatal encephalopathy; brain ischemia; brain hypoxia