Trial Outcomes & Findings for Preemie Hypothermia for Neonatal Encephalopathy (NCT NCT01793129)

Last Updated: 2024-11-04

Results Overview

Severe disability was defined by any of the following: a Bayley III cognitive score \< 70 or Gross Motor Function (GMF) Level of 3-5 blindness or profound hearing loss requiring amplification but still unable to following commands/communicate. Moderate disability was defined as a Bayley III cognitive score between 70-84 and either a GMF level of 2 or a seizure disorder or a hearing deficit.

Recruitment status

COMPLETED

Study phase

Target enrollment

168 participants

Primary outcome timeframe

Birth to 18-22 months corrected age

Results posted on

2024-11-04

Participant Flow

Participant milestones

Participant milestones
Measure	Whole-body Hypothermia Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours Hypothermia: Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours	Normothermia Control group (with esophageal temperature at or near 37.0°C) for 72 hours Normothermic Control: Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Overall Study STARTED	88	80
Overall Study COMPLETED	85	71
Overall Study NOT COMPLETED	3	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Whole-body Hypothermia Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours Hypothermia: Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours	Normothermia Control group (with esophageal temperature at or near 37.0°C) for 72 hours Normothermic Control: Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Overall Study Lost to Follow-up	3	7
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Preemie Hypothermia for Neonatal Encephalopathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Whole-body Hypothermia n=88 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours Hypothermia: Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours	Normothermia n=80 Participants Control group (with esophageal temperature at or near 37.0°C) for 72 hours Normothermic Control: Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours	Total n=168 Participants Total of all reporting groups
Age, Continuous	4.5 Hours STANDARD_DEVIATION 1.2 • n=5 Participants	4.5 Hours STANDARD_DEVIATION 1.3 • n=7 Participants	4.5 Hours STANDARD_DEVIATION 1.3 • n=5 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	35 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	45 Participants n=7 Participants	91 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	10 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	71 Participants n=5 Participants	67 Participants n=7 Participants	138 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	27 Participants n=5 Participants	31 Participants n=7 Participants	58 Participants n=5 Participants
Race (NIH/OMB) White	52 Participants n=5 Participants	42 Participants n=7 Participants	94 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	88 participants n=5 Participants	80 participants n=7 Participants	168 participants n=5 Participants
Level of Encephalopathy Moderate	61 Participants n=5 Participants	57 Participants n=7 Participants	118 Participants n=5 Participants
Level of Encephalopathy Severe	27 Participants n=5 Participants	23 Participants n=7 Participants	50 Participants n=5 Participants
Birthweight	2463.5 grams STANDARD_DEVIATION 634.3 • n=5 Participants	2371.4 grams STANDARD_DEVIATION 607.9 • n=7 Participants	2419.6 grams STANDARD_DEVIATION 621.7 • n=5 Participants
Length	46.0 cm STANDARD_DEVIATION 3.2 • n=5 Participants	45.1 cm STANDARD_DEVIATION 2.8 • n=7 Participants	45.6 cm STANDARD_DEVIATION 3.1 • n=5 Participants
Gestational Age	34.0 Weeks STANDARD_DEVIATION 0.8 • n=5 Participants	34.1 Weeks STANDARD_DEVIATION 0.8 • n=7 Participants	34 Weeks STANDARD_DEVIATION .8 • n=5 Participants

PRIMARY outcome

Timeframe: Birth to 18-22 months corrected age

Population: Includes all infants with primary outcome. Does not include 10 lost to follow up, 4 infants without outcome because the Bayley test was not completed, and 2 infants who withdrew from the study.

Outcome measures

Outcome measures
Measure	Whole-body Hypothermia n=83 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours Hypothermia: Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours	Normothermia n=69 Participants Control group (with esophageal temperature at or near 37.0°C) for 72 hours Normothermic Control: Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Death or Moderate or Severe Disability	29 Participants	20 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrected age

Population: Includes all infants with primary outcome. Does not include 10 lost to follow up and 2 infants who withdrew from the study. Also excluded 4 infants without primary outcome because the Bayley test was not completed, so results can be compared with primary outcome which includes death. These 4 infants without primary outcome because the Bayley test was not completed are in the all-cause mortality summary in the Adverse Events module.

Number of deaths in the NICU and following discharge among infants with a primary outcome.

Outcome measures

Outcome measures
Measure	Whole-body Hypothermia n=83 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours Hypothermia: Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours	Normothermia n=69 Participants Control group (with esophageal temperature at or near 37.0°C) for 72 hours Normothermic Control: Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Deaths in the NICU and Following Discharge	18 Participants	9 Participants

SECONDARY outcome

Timeframe: Post-intervention to through discharge, death, or transfer (whichever comes first), average of 29 days

Population: Infants who had at least one MRI post-intervention

An MRI was considered abnormal if any abnormal findings were indicated on the CRF form.

Outcome measures

Outcome measures
Measure	Whole-body Hypothermia n=75 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours Hypothermia: Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours	Normothermia n=67 Participants Control group (with esophageal temperature at or near 37.0°C) for 72 hours Normothermic Control: Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Infants With Abnormal MRIs During Post-intervention Period	48 Participants	50 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrrected age

Population: infants who were alive at 18-22 months corrected age.

Number of infants with moderate or severe disability among survivors through 18-22 months corrected age.

Outcome measures

Outcome measures
Measure	Whole-body Hypothermia n=65 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours Hypothermia: Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours	Normothermia n=60 Participants Control group (with esophageal temperature at or near 37.0°C) for 72 hours Normothermic Control: Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Infants With Moderate or Severe Disability	11 Participants	11 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrrected age

Causes of any deaths that occurred through 18-22 months corrected age.

Outcome measures

Outcome measures
Measure	Whole-body Hypothermia n=18 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours Hypothermia: Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours	Normothermia n=9 Participants Control group (with esophageal temperature at or near 37.0°C) for 72 hours Normothermic Control: Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Causes of Death Asphyxial Brain Injury	14 Participants	4 Participants
Causes of Death Multi-organ Failure	2 Participants	2 Participants
Causes of Death Cardiomyopathy	1 Participants	0 Participants
Causes of Death Complications of HIE	1 Participants	0 Participants
Causes of Death BPD/CLD	0 Participants	1 Participants
Causes of Death Secondary to severe HIE	0 Participants	1 Participants
Causes of Death Pulmonary Hypoplasia	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Within 6 hours of life to 72 hours after start of intervention

Population: Infants who had at least one cranial ultrasound during intervention.

Infants with recorded events of intraventricular hemorrhage grade I, II, III, or IV, posterior fossa hemorrhage with/without shift of midline structures, intraparenchymal hemorrhage.

Outcome measures

Outcome measures
Measure	Whole-body Hypothermia n=74 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours Hypothermia: Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours	Normothermia n=67 Participants Control group (with esophageal temperature at or near 37.0°C) for 72 hours Normothermic Control: Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Neurological Injury by Cranial Ultrasound During Intervention	2 Participants	3 Participants

Adverse Events

Whole-body Hypothermia

Serious events: 29 serious events

Other events: 22 other events

Deaths: 18 deaths

Normothermia

Serious events: 17 serious events

Other events: 12 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Whole-body Hypothermia n=88 participants at risk Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours Hypothermia: Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 72 hours	Normothermia n=78 participants at risk Control group (with esophageal temperature at or near 37.0°C) for 72 hours Normothermic Control: Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Cardiac disorders Arrhythmia needing treatment	0.00% 0/88 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.	1.3% 1/78 • Number of events 1 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.
Metabolism and nutrition disorders Persistent metabolic acidosis	1.1% 1/88 • Number of events 2 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.	0.00% 0/78 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.
Nervous system disorders Intracranial bleeding	1.1% 1/88 • Number of events 1 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.	0.00% 0/78 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.
Blood and lymphatic system disorders Thrombocytopenia	6.8% 6/88 • Number of events 6 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.	3.8% 3/78 • Number of events 3 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.
Skin and subcutaneous tissue disorders Erythema	4.5% 4/88 • Number of events 4 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.	1.3% 1/78 • Number of events 1 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.
Congenital, familial and genetic disorders PPHN	1.1% 1/88 • Number of events 1 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.	0.00% 0/78 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.
Metabolism and nutrition disorders Hyperglycemia	17.0% 15/88 • Number of events 15 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.	10.3% 8/78 • Number of events 8 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.
Metabolism and nutrition disorders Hypoglycemia	1.1% 1/88 • Number of events 1 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.	3.8% 3/78 • Number of events 3 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.
Vascular disorders Bilateral mIneralizing vasculopathy	0.00% 0/88 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.	1.3% 1/78 • Number of events 1 • SAEs and Other AEs were collected up to 108 hours after baseline. All-cause mortality was collected until 18-22 months corrected age. SAEs and Other AEs were collected up to 108 hours after baseline. Two randomized infants who withdrew prior to initiation of treatment are excluded from SAE and other AE counting.

Additional Information

Dr. Abhik Das

RTI International

Phone: 301-770-8214

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place