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 ]

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

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

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

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

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

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

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


  Serious Adverse Events
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Time Frame Adverse events were reported from the time of the second eligibility assessment to the time of discharge from the acute-care hospital. Generally patients were discharged from the acute care hospital within 3 months of admission.
Additional Description No text entered.

Reporting Groups
  Description
Randomized to Hypothermia and Hypothermia Maintained Induction and maintenance of moderate hypothermia and not excluded by second set of exclusion criteria
Randomized to Normothermia and Normothermia Maintained Induction and maintenance of normothermia and not excluded by second set of exclusion criteria
Randomized to Hypothermia and Then Excluded Induction and maintenance of moderate hypothermia before trauma evaluation in ED and then excluded by second set of criteria
Randomized to Normothermia Then Excluded Maintenance of normothermia before trauma evaluation in ED and then excluded by second set of criteria

Serious Adverse Events
    Randomized to Hypothermia and Hypothermia Maintained     Randomized to Normothermia and Normothermia Maintained     Randomized to Hypothermia and Then Excluded     Randomized to Normothermia Then Excluded  
Total, serious adverse events          
# participants affected / at risk     30/52 (57.69%)     20/45 (44.44%)     11/67 (16.42%)     5/68 (7.35%)  
Cardiac disorders          
Hypotension † 1 [3]        
# participants affected / at risk     1/52 (1.92%)     0/45 (0.00%)     1/67 (1.49%)     0/68 (0.00%)  
# events     6     0     1     0  
Cardiac Arrest † 1 [4]        
# participants affected / at risk     1/52 (1.92%)     1/45 (2.22%)     1/67 (1.49%)     0/68 (0.00%)  
# events     1     1     1     0  
General disorders          
Hypothermia † 1 [5]        
# participants affected / at risk     1/52 (1.92%)     0/45 (0.00%)     0/67 (0.00%)     0/68 (0.00%)  
# events     1     0     0     0  
Multiple Organ Dysfunction † 1 [6]        
# participants affected / at risk     1/52 (1.92%)     1/45 (2.22%)     1/67 (1.49%)     0/68 (0.00%)  
# events     1     1     1     0  
Clinical Sepsis † [7]        
# participants affected / at risk     0/52 (0.00%)     0/45 (0.00%)     1/67 (1.49%)     0/68 (0.00%)  
# events     0     0     1     0  
Infections and infestations          
Blood Stream Infection † 1 [8]        
# participants affected / at risk     0/52 (0.00%)     2/45 (4.44%)     3/67 (4.48%)     3/68 (4.41%)  
# events     0     2     4     3  
Catheter Positive Culture † 1 [9]        
# participants affected / at risk     0/52 (0.00%)     1/45 (2.22%)     0/67 (0.00%)     0/68 (0.00%)  
# events     0     1     0     0  
Nervous system disorders          
Elevated Intracranial Pressure † 1 [10]        
# participants affected / at risk     14/52 (26.92%)     9/45 (20.00%)     4/67 (5.97%)     0/68 (0.00%)  
# events     91     20     7     0  
Decreased Cerebral Perfusion Pressure † 1 [11]        
# participants affected / at risk     21/52 (40.38%)     13/45 (28.89%)     4/67 (5.97%)     0/68 (0.00%)  
# events     46     34     15     0  
Subdural Hemorrhage † 1 [12]        
# participants affected / at risk     1/52 (1.92%)     1/45 (2.22%)     0/67 (0.00%)     0/68 (0.00%)  
# events     1     1     0     0  
Intraparenchymal Hemorrhage † 1 [13]        
# participants affected / at risk     1/52 (1.92%)     0/45 (0.00%)     0/67 (0.00%)     0/68 (0.00%)  
# events     1     0     0     0  
Tentorial Herniation † 1 [14]        
# participants affected / at risk     0/52 (0.00%)     1/45 (2.22%)     0/67 (0.00%)     1/68 (1.47%)  
# events     0     1     0     1  
Epidural Hemorrhage † [15]        
# participants affected / at risk     0/52 (0.00%)     0/45 (0.00%)     0/67 (0.00%)     1/68 (1.47%)  
# events     0     0     0     1  
Respiratory, thoracic and mediastinal disorders          
Pulmonary Embolism † 1 [16]        
# participants affected / at risk     2/52 (3.85%)     0/45 (0.00%)     0/67 (0.00%)     0/68 (0.00%)  
# events     2     0     0     0  
Acute Respiratory Distress Syndrome † 1 [17]        
# participants affected / at risk     2/52 (3.85%)     2/45 (4.44%)     1/67 (1.49%)     0/68 (0.00%)  
# events     2     2     1     0  
Hypoxemia † 1 [18]        
# participants affected / at risk     1/52 (1.92%)     0/45 (0.00%)     0/67 (0.00%)     1/68 (1.47%)  
# events     1     0     0     1  
Hemothorax † 1 [19]        
# participants affected / at risk     1/52 (1.92%)     0/45 (0.00%)     1/67 (1.49%)     0/68 (0.00%)  
# events     1     0     1     0  
Pneumothorax † 1 [20]        
# participants affected / at risk     0/52 (0.00%)     1/45 (2.22%)     0/67 (0.00%)     0/68 (0.00%)  
# events     0     1     0     0  
Events were collected by systematic assessment
1 Term from vocabulary, Standard Terminology
[3] systolic blood pressure < 90 mm Hg or Mean Arterial Pressure < 70 mm Hg for 2 or more consecutive hours associated with end-organ failure due to hypo-perfusion
[4] sudden or unexpected cessation of pumping action of the heart
[5] rectal or core temperature less than or equal to 32 degrees C for any period of time not induced or related to general anesthesia
[6] a pattern of simultaneous or near simultaneous organ failure in at least 3 organ systems.
[7] At least one of following: fever > 38 degrees C SBP < 90 mmHg oliguria (< 20 cc/hr) AND blood culture NOT done or NO organisms in blood no apparent infection at another site physician institutes treatment for sepsis
[8] Has a recognized pathogen from 1 or more blood cultures and organism is not related to infection at another site; or has fever >38C or chills or hypotension and positive blood culture
[9] >15 colonies of pathogenic microorganisms cultured from an arterial or central venous catheter tip associated with clinical sepsis or laboratory-confirmed bloodstream infection
[10] Intracranial pressure levels greater than 30mmHg for more than 30 minutes or levels greater than 40 mmHg for 5 minutes, non-responsive to maximal medical management and requires initiation of barbiturate coma.
[11] Cerebral perfusion pressure <50 mmHg for each occurrence documented on the physiology case report form during hourly data collection
[12] New hemorrhage into subdural space requiring surgery
[13] New hemorrhage into brain tissue requiring surgery
[14] acute clinical neurologic deterioration with pupillary dilation
[15] New hemorrhage into epidural space. (Does not include EDH from initial injury but includes a re-bleed into the previously evacuated surgical site
[16] acute hypoxia associated with high probability ventilation-perfusion scan, positive Spiral CT scan, computed tomography angiography or MRI associated with hypotension or persistent SaO2 less than 90% for greater than or equal to 2 hours
[17] Presence of all 3 of the following; bilateral pulmonary infiltrates a PCWP<18 mm Hg a consistent PO2:FiO2 ratio of <200 for greater than or equal to 3 hours
[18] pO2 <50 mm Hg on greater than or equal to 70% FIO2 or persistent O2 saturation <94% for greater than or equal to 2 hours
[19] presence of blood in the pleural cavity which is not present on admission chest x-ray which drains >200 ml/hr for greater than or equal to 2 hours
[20] Presence of air in the pleural cavity which is not present on admission x-ray associated with hypoxemia or respiratory distress




  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