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Effects of Hypothermia Upon Outcomes After Acute Traumatic Brain Injury (NABIS:HIIR)

This study has been terminated.
(Futility)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Guy Clifton, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT00178711
First received: September 13, 2005
Last updated: September 13, 2014
Last verified: September 2014
Results First Received: July 31, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Traumatic Brain Injury
Intervention: Device: Hypothermia

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were enrolled in hospitals of University of Texas Health Science Center at Houston, University of Calgary, University of Pittsburgh, St. Louis University, Charleston Area Medical Center, and University of New Mexico.Enrollment occurred from December 2005 to June 2009 with follow-up from June 2006 through December 2009

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrollment criteria at the first eligibility assessment were ages 16–45, non-penetrating brain injury, and not responsive to instructions. 232 participants met these criteria and also had none of a first set of exclusion criteria. At the second eligibility assessment, 97 patients had none of a second set of exclusion criteria.

Reporting Groups
  Description
Hypothermia

There were two sets of exclusion criteria-one in the field; the other after resuscitation in the ER. In the field, patients were excluded for suspected pregnancy, systolic blood pressure <110 mm Hg, diastolic blood pressure <60 mm Hg, sustained heart rate >120 beats per minute, or failure to be reached by study-affiliated personnel within 2.5 hours of injury.

Those that did not have any of the first set of exclusion criteria were further assessed for the presence of Glasgow Coma Scale 3-8 without life-threatening associated injuries. The second set of exclusion criteria were GCS 3 with nonreactive pupils, GCS 7-8 with normal brain CT scan, inability to obtain an accurate GCS, Abbreviated Injury Severity Score >4 for organs other than brain4, systolic blood pressure <110 mm Hg or diastolic blood pressure <60 mm Hg, persistent hypoxia, (oxygen saturation < 94%), or positive pregnancy test.

Control 45 patients who had none of the second set of exclusion criteria and who has been randomized to normothermia served as the control group

Participant Flow:   Overall Study
    Hypothermia     Control  
STARTED     52     45  
COMPLETED     52     45  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
hypothermia group-- 26 ± 9 years of age, 40 males/12 females normothermia group--31 ± 11 year of age, 41 males/4 females

Reporting Groups
  Description
Hypothermia

Induction and maintenance of moderate hypothermia to 33 degrees celsius achieved within 4 hours of injury and maintained for 48 hours.

Hypothermia: Induction of moderate hypothermia to 33 degrees celsius, within 4 hours from time of injury and maintained for 48 hours

Control Treated at normothermia
Total Total of all reporting groups

Baseline Measures
    Hypothermia     Control     Total  
Number of Participants  
[units: participants]
  52     45     97  
Age  
[units: years]
Mean ± Standard Deviation
  26  ± 9     31  ± 11     28  ± 10  
Age  
[units: participants]
     
<=18 years     7     6     13  
Between 18 and 65 years     45     38     83  
>=65 years     0     1     1  
Gender  
[units: participants]
     
Female     12     4     16  
Male     40     41     81  



  Outcome Measures

1.  Primary:   The Dichotomized Glasgow Outcome Scale   [ Time Frame: 6 months with a window of plus or minus one month ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title The Dichotomized Glasgow Outcome Scale
Measure Description The primary outcome measure was the Glasgow Outcome Scale measured in person six months after injury by examiners who were blinded to the patient's treatment group. Good recovery and moderate disability were designated as favorable outcomes; severe disability, a vegetative state, and death as poor outcomes.
Time Frame 6 months with a window of plus or minus one month  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat

Reporting Groups
  Description
Hypothermia

Induction and maintenance of moderate hypothermia to 33 degrees celsius achieved within 4 hours of injury and maintained for 48 hours.

Hypothermia: Induction of moderate hypothermia to 33 degrees celsius, within 4 hours from time of injury and maintained for 48 hours

Control treated at normothermia

Measured Values
    Hypothermia     Control  
Number of Participants Analyzed  
[units: participants]
  52     45  
The Dichotomized Glasgow Outcome Scale  
[units: participants with a poor outcome]
  31     25  


Statistical Analysis 1 for The Dichotomized Glasgow Outcome Scale
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] =0.67
Risk Ratio (RR) [4] 1.08
95% Confidence Interval ( 0.76 to 1.53 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The primary hypothesis was a two-sided test assessing whether the induction of hypothermia modified the percentage of subjects with poor outcomes at 6 months after injury. Percentages in each group were compared using a generalized linear model with a binomial distribution and log link function, logistic regression model with admission age and baseline GCS as covariates.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



2.  Other Pre-specified:   Glasgow Outcome Scale - Extended   [ Time Frame: 0-12 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

3.  Other Pre-specified:   Disability Rating Scale   [ Time Frame: assessed 0-12 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

4.  Other Pre-specified:   Neurobehavioral Rating Scale – Revised   [ Time Frame: 0-12 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

5.  Other Pre-specified:   Neurological Outcome Scale for Traumatic Brain Injury   [ Time Frame: 0-12 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

6.  Other Pre-specified:   Symbol Digit Modalities Test   [ Time Frame: 0-12 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

7.  Other Pre-specified:   Rey Osterrieth Complex Figure   [ Time Frame: 0-12 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

8.  Other Pre-specified:   Verbal Selective Reminding Test Trails B   [ Time Frame: 0-12 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

9.  Other Pre-specified:   Grooved Pegboard   [ Time Frame: 0-12 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

10.  Other Pre-specified:   Controlled Oral Word Association Test   [ Time Frame: 0-12 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Early termination for futility.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.


Results Point of Contact:  
Name/Title: Guy L Clifton
Organization: University of Texas Health Science Center
phone: 2024224824
e-mail: guy@guyclifton.com


Publications of Results:
Publications automatically indexed to this study:

Responsible Party: Guy Clifton, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT00178711     History of Changes
Other Study ID Numbers: 5U01 NS043353-06, FDA-2014-109
Study First Received: September 13, 2005
Results First Received: July 31, 2014
Last Updated: September 13, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration