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Trial record 29 of 31 for:    Developmental Disabilities | ( Map: Alabama, United States )

Optimizing (Longer, Deeper) Cooling for Neonatal Hypoxic-Ischemic Encephalopathy(HIE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01192776
Recruitment Status : Terminated (The trial closed for emerging safety profile and futility analysis and will not resume.)
First Posted : September 1, 2010
Results First Posted : August 15, 2017
Last Update Posted : April 9, 2019
Sponsor:
Collaborators:
National Center for Research Resources (NCRR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
NICHD Neonatal Research Network

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Infant, Newborn
Hypoxia, Brain
Hypoxia-Ischemia, Brain
Encephalopathy, Hypoxic-Ischemic
Hypoxic-Ischemic Encephalopathy
Ischemic-Hypoxic Encephalopathy
Intervention Procedure: Whole-body Cooling
Enrollment 364
Recruitment Details 1261 infants assessed for eligibility. 897 were excluded for not meeting eligibility criteria (N=747) or not having parental or physician consent (N=150).
Pre-assignment Details All eligible infants with consent were randomized to one of four treatment arms/groups.
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Period Title: Overall Study
Started 95 90 96 83
Died Prior to Discharge 7 13 15 14
Died After Discharge 1 2 3 1
Completed 84 69 75 63
Not Completed 11 21 21 20
Reason Not Completed
Death             8             15             18             15
Lost to Follow-up             3             6             3             5
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours Total
Hide Arm/Group Description

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Total of all reporting groups
Overall Number of Baseline Participants 95 90 96 83 364
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Hours
Number Analyzed 95 participants 90 participants 95 participants 83 participants 363 participants
5.1  (1.0) 4.9  (1.2) 4.8  (1.1) 5.0  (1.6) 4.9  (1.2)
[1]
Measure Description: Age at Randomization
[2]
Measure Analysis Population Description: Data was missing for one participant.
Sex/Gender, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Male Number Analyzed 95 participants 90 participants 96 participants 83 participants 364 participants
52
  54.7%
53
  58.9%
51
  53.1%
56
  67.5%
212
  58.2%
Female Number Analyzed 95 participants 90 participants 96 participants 83 participants 364 participants
43
  45.3%
37
  41.1%
44
  45.8%
27
  32.5%
151
  41.5%
Ambiguous Number Analyzed 95 participants 90 participants 96 participants 83 participants 364 participants
0
   0.0%
0
   0.0%
1
   1.0%
0
   0.0%
1
   0.3%
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Black Number Analyzed 95 participants 89 participants 94 participants 80 participants 358 participants
29
  30.5%
28
  31.5%
32
  34.0%
25
  31.3%
114
  31.8%
White Number Analyzed 95 participants 89 participants 94 participants 80 participants 358 participants
60
  63.2%
56
  62.9%
55
  58.5%
48
  60.0%
219
  61.2%
Other Number Analyzed 95 participants 89 participants 94 participants 80 participants 358 participants
6
   6.3%
5
   5.6%
7
   7.4%
7
   8.8%
25
   7.0%
[1]
Measure Analysis Population Description: Data was missing for six participants.
Birthweight   [1] 
Mean (Standard Deviation)
Unit of measure:  Grams
Number Analyzed 95 participants 90 participants 95 participants 83 participants 363 participants
3230  (528) 3360  (544) 3354  (676) 3511  (615) 3359  (599)
[1]
Measure Analysis Population Description: Data was missing for one participant.
Level of encephalopathy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 95 participants 90 participants 96 participants 83 participants 364 participants
Moderate
74
  77.9%
70
  77.8%
78
  81.3%
58
  69.9%
280
  76.9%
Severe
21
  22.1%
20
  22.2%
18
  18.8%
25
  30.1%
84
  23.1%
1.Primary Outcome
Title Death or Moderate to Severe Disability
Hide Description Death includes any mortality prior to follow up at 18-22 months. Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands.
Time Frame Birth to 22 months corrected age
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all deaths and all infants followed at 18-22 months. Does not include 17 infants lost to follow up.
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 92 84 93 78
Measure Type: Count of Participants
Unit of Measure: Participants
27
  29.3%
29
  34.5%
32
  34.4%
22
  28.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 72 Hours
Comments 32.0°C for 72 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.76 to 1.98
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 33.5°C for 120 Hours
Comments 33.5°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.21
Confidence Interval (2-Sided) 95%
0.78 to 1.87
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 120 Hours
Comments 32.0°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.53 to 1.35
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Death
Hide Description Death includes any mortality prior to follow up at 18-22 months.
Time Frame Birth to 22 months corrected age
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all deaths and all infants followed at 18-22 months. Does not include 17 infants lost to follow up.
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 92 84 93 78
Measure Type: Count of Participants
Unit of Measure: Participants
8
   8.7%
15
  17.9%
18
  19.4%
15
  19.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 72 Hours
Comments 32.0°C for 72 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 2.16
Confidence Interval (2-Sided) 95%
0.55 to 8.49
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 33.5°C for 120 Hours
Comments 33.5°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 2.52
Confidence Interval (2-Sided) 95%
1.06 to 5.95
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 120 Hours
Comments 32.0°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.85
Confidence Interval (2-Sided) 95%
0.79 to 4.31
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Level of Disability Among Survivors
Hide Description

Among survivors number of normal infants and infants with mild, moderate, and severe disability

Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands. Mild impairment was defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMFCS level 1 or 2, seizure disorder or hearing loss not requiring amplification. Normal was defined by a cognitive score ≥ 85 in the absence of any neurosensory deficits or seizures after NICU discharge.

Time Frame Follow up at 18-22 months corrected age
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all infants followed at 18-22 months except for 6 infants who could not be distinguished between normal and mild. Does not include 17 infants lost to follow up or 56 deaths
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 81 69 72 63
Measure Type: Count of Participants
Unit of Measure: Participants
Severe disability
18
  22.2%
11
  15.9%
14
  19.4%
7
  11.1%
Moderate disability
1
   1.2%
3
   4.3%
0
   0.0%
0
   0.0%
Mild disability
16
  19.8%
15
  21.7%
22
  30.6%
18
  28.6%
Normal
46
  56.8%
40
  58.0%
36
  50.0%
38
  60.3%
4.Secondary Outcome
Title Withdrawal of Care
Hide Description Number of infants for whom aggressive care is withdrawn
Time Frame Birth through hospital discharge, average 22 days.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 95 90 96 83
Measure Type: Count of Participants
Unit of Measure: Participants
6
   6.3%
12
  13.3%
14
  14.6%
13
  15.7%
5.Secondary Outcome
Title Clinical Neonatal Seizures
Hide Description Documented seizures during hospital course
Time Frame Through death, discharge, or transfer
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 95 90 96 83
Measure Type: Count of Participants
Unit of Measure: Participants
50
  52.6%
43
  47.8%
44
  45.8%
40
  48.2%
6.Secondary Outcome
Title Bayley Cognitive Score
Hide Description Bayley Scale of Infant Development Composite Cognitive Score. The total composite score is reported, ranging from the lowest score of 55 to the highest score of 145. Lower values specify worse outcome.
Time Frame Follow up at 18-22 months corrected age
Hide Outcome Measure Data
Hide Analysis Population Description
Infants who survived and were followed at 18-22 months
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 78 69 73 63
Median (Inter-Quartile Range)
Unit of Measure: scores on a scale
90
(80 to 100)
90
(75 to 100)
90
(80 to 100)
90
(80 to 95)
7.Secondary Outcome
Title Cerebral Palsy
Hide Description [Not Specified]
Time Frame Follow up at 18-22 months corrected age
Hide Outcome Measure Data
Hide Analysis Population Description
Infants who survived and were followed at 18-22 months
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 83 69 75 63
Measure Type: Count of Participants
Unit of Measure: Participants
15
  18.1%
13
  18.8%
10
  13.3%
8
  12.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 72 Hours
Comments 32.0°C for 72 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.64 to 2.38
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 33.5°C for 120 Hours
Comments 33.5°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.36 to 1.90
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 120 Hours
Comments 32.0°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.26 to 1.57
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Level of Disability Among Survivors, by Level of HIE
Hide Description Among survivors, number of normal infants and infants with mild, moderate and severe disability Severe disability was defined by any of the following: a Bayley III cognitive score <70, a GMFCS level of 3-5, blindness or profound hearing loss (inability to understand commands despite amplification). Moderate disability was defined as a Bayley cognitive score of 70-84 and either a GMFCS level of 2, seizure disorder, or a hearing deficit requiring amplification to understand commands. Mild impairment was defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMFCS level 1 or 2, seizure disorder or hearing loss not requiring amplification. Normal was defined by a cognitive score ≥ 85 in the absence of any neurosensory deficits or seizures after NICU discharge.
Time Frame Follow up at 18-22 months corrected age
Hide Outcome Measure Data
Hide Analysis Population Description
Includes all infants followed at 18-22 months, except for 6 infants who could not be distinguished between normal and mild. Does not include 17 infants lost to follow up or 56 deaths.
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 81 69 72 63
Measure Type: Count of Participants
Unit of Measure: Participants
Moderate HIE Number Analyzed 64 participants 60 participants 65 participants 49 participants
Normal
41
  64.1%
39
  65.0%
34
  52.3%
31
  63.3%
Mild disability
13
  20.3%
12
  20.0%
19
  29.2%
13
  26.5%
Moderate disability
1
   1.6%
2
   3.3%
0
   0.0%
0
   0.0%
Severe disability
9
  14.1%
7
  11.7%
12
  18.5%
5
  10.2%
Severe HIE Number Analyzed 17 participants 9 participants 7 participants 14 participants
Normal
5
  29.4%
1
  11.1%
2
  28.6%
7
  50.0%
Mild disability
3
  17.6%
3
  33.3%
3
  42.9%
5
  35.7%
Moderate disability
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
Severe disability
9
  52.9%
4
  44.4%
2
  28.6%
2
  14.3%
9.Secondary Outcome
Title Visual Impairment
Hide Description Visual impairment is defined as bilateral blindness with some/no useful vision
Time Frame Follow up at 18-22 months corrected age
Hide Outcome Measure Data
Hide Analysis Population Description
Infants who survived and were followed at 18-22 months
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 83 69 75 63
Measure Type: Count of Participants
Unit of Measure: Participants
6
   7.2%
6
   8.7%
2
   2.7%
4
   6.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 72 Hours
Comments 32.0°C for 72 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.33
Confidence Interval (2-Sided) 95%
0.63 to 2.77
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 33.5°C for 120 Hours
Comments 33.5°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.09 to 2.04
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 120 Hours
Comments 32.0°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.20 to 2.99
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Hearing Impairment
Hide Description Hearing impairment is defined as hearing impairment despite amplification
Time Frame Follow up at 18-22 months corrected age
Hide Outcome Measure Data
Hide Analysis Population Description
Infants who survived and were followed at 18-22 months
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 83 69 75 63
Measure Type: Count of Participants
Unit of Measure: Participants
4
   4.8%
2
   2.9%
4
   5.3%
1
   1.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 72 Hours
Comments 32.0°C for 72 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.14 to 3.01
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 33.5°C for 120 Hours
Comments 33.5°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.31
Confidence Interval (2-Sided) 95%
0.44 to 3.91
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 120 Hours
Comments 32.0°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.03 to 2.89
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Multiple Disabilities
Hide Description Multiple disabilities is defined as two or more of the following 5 components: disabling CP, GMFCS level 3-5, Bayley cognitive score < 70, blindness, or deafness.
Time Frame Follow up at 18-22 months corrected age
Hide Outcome Measure Data
Hide Analysis Population Description
Infants who survived and were followed at 18-22 months
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 84 69 75 63
Measure Type: Count of Participants
Unit of Measure: Participants
14
  16.7%
9
  13.0%
7
   9.3%
5
   7.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 72 Hours
Comments 32.0°C for 72 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.37 to 2.07
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 33.5°C for 120 Hours
Comments 33.5°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.30 to 1.35
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 33.5°C for 72 Hours, 32.0°C for 120 Hours
Comments 32.0°C for 120 hours vs. 33.5°C for 72 hours (33.5°C for 72 hours is the comparison group)
Type of Statistical Test Superiority
Comments Generalized Estimating Equations models with log link, adjusted for level of encephalopathy and intra-center correlations
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.13 to 1.64
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Multiorgan Dysfunction
Hide Description The data needed for this analysis are not collected directly, and will not be analyzed as the study was terminated early and no funds available to complete this complex analysis. The data for this study will be stored at the NICHD-DASH for investigators.
Time Frame Until death, discharge, or transfer
Hide Outcome Measure Data
Hide Analysis Population Description
No patients were analyzed for this outcome as the study was terminated early and no additional funds available to complete this complex analysis.
Arm/Group Title 33.5°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 72 Hours 32.0°C for 120 Hours
Hide Arm/Group Description:

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Other Pre-specified Outcome
Title Severe Neonatal Brain Abnormalities
Hide Description

The data for this analysis have not yet been collected.

MRIs taken between 7-14 days will be examined.

Time Frame 7-14 days of life
Outcome Measure Data Not Reported
Time Frame During study intervention period: 72 or 120 hours from baseline, based on treatment arm
Adverse Event Reporting Description 17 infants lost to follow up were excluded from the All-Cause Mortality table. Mortality cannot be assessed for infants lost to follow up.
 
Arm/Group Title 33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Hide Arm/Group Description

Target Temp: 33.5°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration: 72 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 33.5°C Duration: 120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

Target Temp: 32.0°C Duration:120 hrs

Whole-body Cooling: Whole-body cooling using a Blanketrol II or III to reach either a target core temperature of 33.5°C or 32.0°C for a duration of either 72 hours or 120 hours.

All-Cause Mortality
33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/92 (8.70%)      15/84 (17.86%)      18/93 (19.35%)      15/78 (19.23%)    
Show Serious Adverse Events Hide Serious Adverse Events
33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/95 (10.53%)      15/90 (16.67%)      11/96 (11.46%)      23/83 (27.71%)    
Cardiac disorders         
Cardiac Arrythmia   1/95 (1.05%)  1 1/90 (1.11%)  1 1/96 (1.04%)  1 7/83 (8.43%)  9
General disorders         
Other  [1]  5/95 (5.26%)  7 10/90 (11.11%)  10 6/96 (6.25%)  7 11/83 (13.25%)  16
Nervous system disorders         
Death during intervention   5/95 (5.26%)  5 5/90 (5.56%)  5 7/96 (7.29%)  7 12/83 (14.46%)  12
Thrombosis   0/95 (0.00%)  0 0/90 (0.00%)  0 0/96 (0.00%)  0 1/83 (1.20%)  1
Major Bleeding   3/95 (3.16%)  3 2/90 (2.22%)  2 1/96 (1.04%)  1 1/83 (1.20%)  1
Indicates events were collected by systematic assessment
[1]
Other Serious Adverse Events
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
33.5°C for 72 Hours 32.0°C for 72 Hours 33.5°C for 120 Hours 32.0°C for 120 Hours
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/95 (5.26%)      3/90 (3.33%)      6/96 (6.25%)      9/83 (10.84%)    
General disorders         
Metabolic acidosis developing >3 hours after initiation of intervention and persisting >3 hours   2/95 (2.11%)  3 0/90 (0.00%)  0 1/96 (1.04%)  1 4/83 (4.82%)  4
Musculoskeletal and connective tissue disorders         
Alteration of Skin Integrity   3/95 (3.16%)  3 3/90 (3.33%)  3 5/96 (5.21%)  8 5/83 (6.02%)  5
Indicates events were collected by systematic assessment
This RCT was stopped for safety and futility reasons by the Data Safety and Monitoring Committee so did not enroll the target number of participants needed to achieve target power and statistically reliable results.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Investigators must adhere to the Neonatal Research Network Publication policies.
Results Point of Contact
Name/Title: Seetha Shankaran
Organization: Wayne State University
Phone: (313) 745-1436
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: NICHD Neonatal Research Network
ClinicalTrials.gov Identifier: NCT01192776     History of Changes
Other Study ID Numbers: NICHD-NRN-0043
U10HD021364 ( U.S. NIH Grant/Contract )
U10HD021373 ( U.S. NIH Grant/Contract )
U10HD021385 ( U.S. NIH Grant/Contract )
U10HD027851 ( U.S. NIH Grant/Contract )
U10HD027853 ( U.S. NIH Grant/Contract )
U10HD027856 ( U.S. NIH Grant/Contract )
U10HD027871 ( U.S. NIH Grant/Contract )
U10HD027880 ( U.S. NIH Grant/Contract )
U10HD027904 ( U.S. NIH Grant/Contract )
U10HD034216 ( U.S. NIH Grant/Contract )
U10HD036790 ( U.S. NIH Grant/Contract )
U10HD040492 ( U.S. NIH Grant/Contract )
U10HD040689 ( U.S. NIH Grant/Contract )
U10HD053089 ( U.S. NIH Grant/Contract )
U10HD053109 ( U.S. NIH Grant/Contract )
U10HD053119 ( U.S. NIH Grant/Contract )
U10HD053124 ( U.S. NIH Grant/Contract )
UL1RR024139 ( U.S. NIH Grant/Contract )
UL1RR024979 ( U.S. NIH Grant/Contract )
UL1RR025008 ( U.S. NIH Grant/Contract )
UL1RR025744 ( U.S. NIH Grant/Contract )
UL1RR025747 ( U.S. NIH Grant/Contract )
UL1RR025761 ( U.S. NIH Grant/Contract )
UL1RR025764 ( U.S. NIH Grant/Contract )
U10HD068284 ( U.S. NIH Grant/Contract )
U10HD068278 ( U.S. NIH Grant/Contract )
U10HD068270 ( U.S. NIH Grant/Contract )
U10HD068263 ( U.S. NIH Grant/Contract )
U10HD068244 ( U.S. NIH Grant/Contract )
First Submitted: August 31, 2010
First Posted: September 1, 2010
Results First Submitted: March 31, 2017
Results First Posted: August 15, 2017
Last Update Posted: April 9, 2019