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| ID | Type | Description | Link |
|---|---|---|---|
| FDA-2014-109 | Other Identifier | FDA |
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Futility
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| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
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Induction of hypothermia to < 35ËšC by < 2.5 hours after severe traumatic brain injury, reaching 33ËšC by 4 hours after injury and maintained for 48 hours in patients aged 16-45 will result in an increased number of patients with good outcomes at six months after injury compared to patients randomized to normothermia.
NABIS:HIIR was a randomized clinical trial conducted in patients with severe brain injury, age 16-45. Patients were randomized to standard treatment at normothermia or to standard treatment with moderate hypothermia (32.5-34C for 48 hours). An intent to treat analysis was used with the primary outcome measure as the Glasgow Outcome Scale at six months after injury. GOS is dichotomized into good outcome (Good Recovery/Moderate Disability) and poor outcome (Severe Disability, Vegetative, Dead).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| hypothermia | Active Comparator | Induction and maintenance of moderate hypothermia to 33 degrees celsius achieved within 2.5 hours of injury and maintained for 48 hours. |
|
| control | No Intervention | treated at normothermia |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hypothermia | Device | Induction of moderate hypothermia to 33 degrees celsius, within 2.5 hours from time of injury and maintained for 48 hours |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Dichotomized Glasgow Outcome Scale | 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. | 6 months with a window of plus or minus one month |
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| Measure | Description | Time Frame |
|---|---|---|
| Glasgow Outcome Scale - Extended | 0-12 months | |
| Disability Rating Scale | assessed 0-12 months | |
| Neurobehavioral Rating Scale - Revised |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Guy L Clifton, MD | UTHSC-H | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of St Louis : St. Louis University Hospital | St Louis | Missouri | 63110 | United States | ||
| University of Pittsburgh : University of Pittsburgh Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22839656 | Result | Clifton GL, Coffey CS, Fourwinds S, Zygun D, Valadka A, Smith KR Jr, Frisby ML, Bucholz RD, Wilde EA, Levin HS, Okonkwo DO. Early induction of hypothermia for evacuated intracranial hematomas: a post hoc analysis of two clinical trials. J Neurosurg. 2012 Oct;117(4):714-20. doi: 10.3171/2012.6.JNS111690. Epub 2012 Jul 27. | |
| 21169065 | Result | Clifton GL, Valadka A, Zygun D, Coffey CS, Drever P, Fourwinds S, Janis LS, Wilde E, Taylor P, Harshman K, Conley A, Puccio A, Levin HS, McCauley SR, Bucholz RD, Smith KR, Schmidt JH, Scott JN, Yonas H, Okonkwo DO. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol. 2011 Feb;10(2):131-9. doi: 10.1016/S1474-4422(10)70300-8. Epub 2010 Dec 17. |
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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.
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
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
hypothermia group-- 26 ± 9 years of age, 40 males/12 females normothermia group--31 ± 11 year of age, 41 males/4 females
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Dichotomized Glasgow Outcome Scale | 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. | Intention to Treat | Posted | Number | participants with a poor outcome | 6 months with a window of plus or minus one month |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Randomized to Hypothermia and Hypothermia Maintained | Induction and maintenance of moderate hypothermia and not excluded by second set of exclusion criteria |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Intracranial Pressure | Nervous system disorders | Standard Terminology | Systematic Assessment | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Intracranial Pressure | Nervous system disorders | Standard Terminology | Systematic Assessment | Intracranial pressure > 20 mm Hg for 2 or more consecutive hours but that does not meet the definition of critical elevated intracranial pressure (See serious adverse events for that definition) |
Early termination for futility.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Guy L Clifton | University of Texas Health Science Center | 2024224824 | guy@guyclifton.com |
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| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| D007035 | Hypothermia |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D007036 | Hypothermia, Induced |
| ID | Term |
|---|---|
| D017679 | Cryotherapy |
| D013812 | Therapeutics |
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| 0-12 months |
| Neurological Outcome Scale for Traumatic Brain Injury | 0-12 months |
| Symbol Digit Modalities Test | 0-12 months |
| Rey Osterrieth Complex Figure | 0-12 months |
| Verbal Selective Reminding Test Trails B | 0-12 months |
| Grooved Pegboard | 0-12 months |
| Controlled Oral Word Association Test | 0-12 months |
| Pittsburgh |
| Pennsylvania |
| 15213 |
| United States |
| University of Texas Health Science Center, Memorial Hermann Hospital | Houston | Texas | 77030 | United States |
| Charleston Area Medical Center | Charleston | West Virginia | 25304 | United States |
| University of Calgary Health Science Center : Foothills Medical Center | Calgary | Alberta | T2N4N1 | Canada |
| Control |
Treated at normothermia |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Control |
treated at normothermia |
|
|
|
| Other Pre-specified | Glasgow Outcome Scale - Extended | Not Posted | 0-12 months |
| Other Pre-specified | Disability Rating Scale | Not Posted | assessed 0-12 months |
| Other Pre-specified | Neurobehavioral Rating Scale - Revised | Not Posted | 0-12 months |
| Other Pre-specified | Neurological Outcome Scale for Traumatic Brain Injury | Not Posted | 0-12 months |
| Other Pre-specified | Symbol Digit Modalities Test | Not Posted | 0-12 months |
| Other Pre-specified | Rey Osterrieth Complex Figure | Not Posted | 0-12 months |
| Other Pre-specified | Verbal Selective Reminding Test Trails B | Not Posted | 0-12 months |
| Other Pre-specified | Grooved Pegboard | Not Posted | 0-12 months |
| Other Pre-specified | Controlled Oral Word Association Test | Not Posted | 0-12 months |
| 30 |
| 52 |
| 42 |
| 52 |
| EG001 | Randomized to Normothermia and Normothermia Maintained | Induction and maintenance of normothermia and not excluded by second set of exclusion criteria | 20 | 45 | 38 | 45 |
| EG002 | 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 | 11 | 67 | 22 | 67 |
| EG003 | Randomized to Normothermia Then Excluded | Maintenance of normothermia before trauma evaluation in ED and then excluded by second set of criteria | 5 | 68 | 30 | 68 |
|
| Decreased Cerebral Perfusion Pressure | Nervous system disorders | Standard Terminology | Systematic Assessment | Cerebral perfusion pressure <50 mmHg for each occurrence documented on the physiology case report form during hourly data collection |
|
| Subdural Hemorrhage | Nervous system disorders | Standard Terminology | Systematic Assessment | New hemorrhage into subdural space requiring surgery |
|
| Intraparenchymal Hemorrhage | Nervous system disorders | Standard Terminology | Systematic Assessment | New hemorrhage into brain tissue requiring surgery |
|
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | Standard Terminology | Systematic Assessment | 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 |
|
| Acute Respiratory Distress Syndrome | Respiratory, thoracic and mediastinal disorders | Standard Terminology | Systematic Assessment | Presence of all 3 of the following;
|
|
| Hypothermia | General disorders | Standard Terminology | Systematic Assessment | rectal or core temperature less than or equal to 32 degrees C for any period of time not induced or related to general anesthesia |
|
| Multiple Organ Dysfunction | General disorders | Standard Terminology | Systematic Assessment | a pattern of simultaneous or near simultaneous organ failure in at least 3 organ systems. |
|
| Hypoxemia | Respiratory, thoracic and mediastinal disorders | Standard Terminology | Systematic Assessment | 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 |
|
| Hypotension | Cardiac disorders | Standard Terminology | Systematic Assessment | 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 |
|
| Cardiac Arrest | Cardiac disorders | Standard Terminology | Systematic Assessment | sudden or unexpected cessation of pumping action of the heart |
|
| Hemothorax | Respiratory, thoracic and mediastinal disorders | Standard Terminology | Systematic Assessment | 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 |
|
| Tentorial Herniation | Nervous system disorders | Standard Terminology | Systematic Assessment | acute clinical neurologic deterioration with pupillary dilation |
|
| Blood Stream Infection | Infections and infestations | Standard Terminology | Systematic Assessment | 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 |
|
| Catheter Positive Culture | Infections and infestations | Standard Terminology | Systematic Assessment | >15 colonies of pathogenic microorganisms cultured from an arterial or central venous catheter tip associated with clinical sepsis or laboratory-confirmed bloodstream infection |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | Standard Terminology | Systematic Assessment | Presence of air in the pleural cavity which is not present on admission x-ray associated with hypoxemia or respiratory distress |
|
| Epidural Hemorrhage | Nervous system disorders | Systematic Assessment | New hemorrhage into epidural space. (Does not include EDH from initial injury but includes a re-bleed into the previously evacuated surgical site |
|
| Clinical Sepsis | General disorders | Systematic Assessment | 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 |
|
|
| Decreased Cerebral Perfusion Pressure | Nervous system disorders | Standard Terminology | Systematic Assessment | Cerebral perfusion pressure <60 mm Hg for 2 or more consecutive hours but that does not meet the definition of critical decreased perfusion pressure (See serious adverse events for that definition) |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Standard Terminology | Systematic Assessment | new or progressive infiltrated, consolidation or pleural effusion on chest x-ray and at least one of the following:
|
|
| Urinary Tract Infection | Renal and urinary disorders | Standard Terminology | Systematic Assessment | Fever >38C and positive urine culture or physician diagnosis of urinary tract infection |
|
| Deep Vein Thrombosis | Vascular disorders | Standard Terminology | Systematic Assessment | diagnostic (ultrasound, venogram, Doppler studies) evidence of deep vein thrombosis |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | Standard Terminology | Systematic Assessment | presence of air in the pleural cavity which is not present on admission x-ray and is not associated with hypoxemia or respiratory distress |
|
| Decubitus | Skin and subcutaneous tissue disorders | Standard Terminology | Systematic Assessment | new ulceration of the skin and subcutaneous tissue which is pressure-related; code only Stage II ulcers or higher (through epidermis and dermis) |
|
| hypotension | General disorders | Standard Terminology | Systematic Assessment | Systolic blood pressure <90 mm Hg or Mean arterial pressure <70 mm Hg for 2 or more consecutive hours but not associated with end-organ failure due to hypoperfusion (see Serious Adverse events for definition of critical hypotension) |
|
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| D006259 |
| Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D001832 | Body Temperature Changes |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |