Trial Outcomes & Findings for Late Hypothermia for Hypoxic-Ischemic Encephalopathy (NCT NCT00614744)

NCT ID: NCT00614744

Last Updated: 2021-03-09

Results Overview

Severe disability was defined by any of the following: a Bayley III cognitive score \< 70 or Gross Motor Functional (GMF) Level of 3-5 blindness or profound hearing loss requiring amplification but still unable to follow 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: NA
• Target enrollment: 168 participants
• Primary outcome timeframe: Birth to 18-22 months corrected gestational age
• Results posted on: 2021-03-09

Participant Flow

Multicenter randomized trial to evaluate whether induced hypothermia with body cooling initiated between 6-24 hours of age and continued for 96 hours in infants >= 36 weeks gestation with hypoxic-ischemic encephalopathy will reduce the incidence of death or disability at 18 months of age. Eligible infants were enrolled from 05/06/08 to 07/12/14.

Participant milestones

Measure	Whole-body Hypothermia Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Overall Study STARTED	83	85
Overall Study COMPLETED	78	79
Overall Study NOT COMPLETED	5	6

Reasons for withdrawal

Measure	Whole-body Hypothermia Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Overall Study Lost to Follow-up	5	4
Overall Study Incomplete for Behavior Issues	0	2

Baseline Characteristics

Late Hypothermia for Hypoxic-Ischemic Encephalopathy

Baseline characteristics by cohort

Measure	Whole-body Hypothermia n=83 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=85 Participants 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, Customized <= 12 Hours	26 Participants n=5 Participants	28 Participants n=7 Participants	54 Participants n=5 Participants
Age, Customized > 12 Hours	57 Participants n=5 Participants	57 Participants n=7 Participants	114 Participants n=5 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	55 Participants n=7 Participants	102 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	30 Participants n=7 Participants	66 Participants n=5 Participants
Level of Encephalopathy Moderate	73 Participants n=5 Participants	78 Participants n=7 Participants	151 Participants n=5 Participants
Level of Encephalopathy Severe	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Birthweight	3379 grams STANDARD_DEVIATION 528 • n=5 Participants	3303 grams STANDARD_DEVIATION 553 • n=7 Participants	3340 grams STANDARD_DEVIATION 541 • n=5 Participants
Length	51 centimeters STANDARD_DEVIATION 3 • n=5 Participants	51 centimeters STANDARD_DEVIATION 3 • n=7 Participants	51 centimeters STANDARD_DEVIATION 3 • n=5 Participants
Gestational Age	39 weeks STANDARD_DEVIATION 2 • n=5 Participants	39 weeks STANDARD_DEVIATION 1 • n=7 Participants	39 weeks STANDARD_DEVIATION 1 • n=5 Participants

PRIMARY outcome

Timeframe: Birth to 18-22 months corrected gestational age

Population: Does not include 9 lost to follow up and 2 infants without outcome for behavior issues

Severe disability was defined by any of the following: a Bayley III cognitive score < 70 or Gross Motor Functional (GMF) Level of 3-5 blindness or profound hearing loss requiring amplification but still unable to follow 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.

Outcome measures

Measure	Whole-body Hypothermia n=78 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=79 Participants Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Death or Moderate or Severe Disability	19 Participants	22 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrected gestational age

Population: Does not include 9 lost to follow up and 2 infants without outcome for behavior issues

Outcome measures

Measure	Whole-body Hypothermia n=78 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=79 Participants Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Deaths in the NICU and Following Discharge	9 Participants	9 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrected gestational age

Population: Does not include 9 lost to follow up and 2 infants without outcome for behavior issues

Moderate disability will be 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. Severe disability will be defined by any of the following: a Bayley III cognitive score < 70 or Gross Motor Functional (GMF) Level of 3-5 or blindness or profound hearing loss requiring amplification but still unable to follow commands/communicate.

Outcome measures

Measure	Whole-body Hypothermia n=78 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=79 Participants Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Infants With Moderate and Severe Disability	10 Participants	13 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrected gestational age

Population: Does not include 9 lost to follow up and 2 infants without outcome for behavior issues

Mild disability will be defined by either a Bayley III cognitive score of 70-84 alone or a Bayley III cognitive score >= 85 and any of the following: presence of a GMF level 1 or 2 OR seizure disorder or hearing loss. 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. Severe disability will be defined by any of the following: a Bayley III cognitive score < 70 OR Gross Motor Functional (GMF) Level of 3-5 OR blindness or profound hearing loss requiring amplification but still unable to follow commands/communicate.

Outcome measures

Measure	Whole-body Hypothermia n=78 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=79 Participants Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Infants With Mild, Moderate and Severe Disability	26 Participants	25 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrected gestational age

Mild disability will be defined by either a Bayley III cognitive score of 70-84 alone or a Bayley III cognitive score >= 85 and any of the following: presence of a GMF level 1 or 2OR seizure disorder or hearing loss. 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. Severe disability will be defined by any of the following: a Bayley III cognitive score < 70 OR Gross Motor Functional (GMF) Level of 3-5 OR blindness or profound hearing loss requiring amplification but still unable to follow commands/communicate.

Outcome measures

Measure	Whole-body Hypothermia n=69 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=70 Participants Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Infants With Any Disability Based on Level of Encephalopathy at Randomization Moderate encephalopathy	24 Participants	25 Participants
Number of Infants With Any Disability Based on Level of Encephalopathy at Randomization Severe encephalopathy	2 Participants	0 Participants
Number of Infants With Any Disability Based on Level of Encephalopathy at Randomization Total	26 Participants	25 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrected gestational age

Based on observing presence of organ dysfunction on at least one of the following: Pulmonary (Meconium aspiration syndrome, PPHN, Pulmonary hemorrhage, Pneumonia, Chronic lung disease, ECMO, INO), Cardiovascular (Cardiomegaly, Cardiac failure, Cardiac dysfunction (by echo), Cardiac ischemia (by EKG and/or increased enzymes), Hypotension, Arrhythmia), Renal (Oliguria, Anuria, Dialysis), Gastrointestinal (NEC, Hepatic dysfunction), Hematologic (DIC) and Metabolic (Hypoglycemia, Hypocalcemia, Hypomagnesemia)

Outcome measures

Measure	Whole-body Hypothermia n=83 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=85 Participants Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Infants With Non-CNS Organ System Dysfunction	63 Participants	59 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrected gestational age

Outcome measures

Measure	Whole-body Hypothermia n=83 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=85 Participants Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Infants With a DNR Order	7 Participants	8 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrected gestational age

Outcome measures

Measure	Whole-body Hypothermia n=83 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=85 Participants Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Infants With a DNR Order and Support is Withdrawn	6 Participants	8 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrected gestational age

Population: Only infants with DNR order

Outcome measures

Measure	Whole-body Hypothermia n=83 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=85 Participants Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Infants With a DNR Order That Died	5 Participants	7 Participants

SECONDARY outcome

Timeframe: Birth to 18-22 months corrected gestational age

Outcome measures

Measure	Whole-body Hypothermia n=83 Participants Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=85 Participants Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Number of Infants With Neonatal Seizures, With and Without EEG Abnormalities	63 Participants	56 Participants

Adverse Events

Whole-body Hypothermia

Serious events: 5 serious events

Other events: 0 other events

Deaths: 6 deaths

Normothermia

Serious events: 1 serious events

Other events: 0 other events

Deaths: 5 deaths

Serious adverse events

Measure	Whole-body Hypothermia n=83 participants at risk Induced Whole-body hypothermia (with a target esophageal temperature of 33.5°C) for 96 hours	Normothermia n=85 participants at risk Normothermic Control group (with esophageal temperature at or near 37.0°C) for 96 hours
Vascular disorders Bleeding	4.8% 4/83 • Number of events 4 • During study intervention period: 124 hours from baseline (time of insertion of esophageal probe).	1.2% 1/85 • Number of events 1 • During study intervention period: 124 hours from baseline (time of insertion of esophageal probe).
Skin and subcutaneous tissue disorders Alteration of skin integrity	1.2% 1/83 • Number of events 1 • During study intervention period: 124 hours from baseline (time of insertion of esophageal probe).	0.00% 0/85 • During study intervention period: 124 hours from baseline (time of insertion of esophageal probe).
Respiratory, thoracic and mediastinal disorders PPHN/Acidosis	2.4% 2/83 • Number of events 2 • During study intervention period: 124 hours from baseline (time of insertion of esophageal probe).	0.00% 0/85 • During study intervention period: 124 hours from baseline (time of insertion of esophageal probe).

Other adverse events

Adverse event data not reported

Additional Information

Abbot Laptook

Brown University, Women & Infants Hospital of Rhode Island

Phone: 401-274-1122

Email: alaptook@wihri.org

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators must adhere to the Neonatal Research Network Publication policies.
• Publication restrictions are in place

Restriction type: OTHER