Trial Outcomes & Findings for Hypertonic Resuscitation Following Severe Traumatic Brain Injury (TBI) (NCT NCT00316004)

NCT ID: NCT00316004

Last Updated: 2011-05-19

Results Overview

Glasgow outcome score extended (GOSE) contains eight categories: 1. Dead, 2. Vegetative State (VS), 3. Lower Severe Disability (Lower SD), 4. Upper Severe Disability (Upper SD), 5. Lower Moderate Disability (Lower MD), 6. Upper Moderate Disability (Upper MD), 7. Lower Good Recovery (Lower GR) and 8. Upper Good Recovery (Upper GR). A measured neurological outcome of GOSE≤4 is a poor outcome of severe disability, vegetative state, or death. Completer analysis includes only those patients with GOSE completed at 6 months after injury.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 1331 participants
• Primary outcome timeframe: 6 months after injury
• Results posted on: 2011-05-19

Participant Flow

Subjects were enrolled by Emergency Medicine Services (EMS) personnel in the prehospital setting based on pre-defined inclusion/exclusion criteria. The first subject was enrolled in May 2006. The last subject was enrolled in May 2009.

1331 subjects were randomized. 1282 were included in primary imputation analysis. 49 were randomized with study fluid package opened but no study fluid was given. Reasons given were: Did not meet inclusion criteria; Met an exclusion criterion; No intravenous access; Fluid bag sterility broken; EMS responder unsure of inclusion/exclusion criteria.

Participant milestones

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Overall Study STARTED	373	355	603
Overall Study COMPLETED	359	341	582
Overall Study NOT COMPLETED	14	14	21

Reasons for withdrawal

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Overall Study Subject was not given study fluid.	14	14	21

Baseline Characteristics

Hypertonic Resuscitation Following Severe Traumatic Brain Injury (TBI)

Baseline characteristics by cohort

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=373 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=355 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=603 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	Total n=1331 Participants Total of all reporting groups
Age Categorical <=18 years	33 participants n=5 Participants	19 participants n=7 Participants	43 participants n=5 Participants	95 participants n=4 Participants
Age Categorical Between 18 and 65 years	296 participants n=5 Participants	305 participants n=7 Participants	484 participants n=5 Participants	1085 participants n=4 Participants
Age Categorical >=65 years	41 participants n=5 Participants	29 participants n=7 Participants	74 participants n=5 Participants	144 participants n=4 Participants
Age Continuous	38.5 years STANDARD_DEVIATION 18.6 • n=5 Participants	38.6 years STANDARD_DEVIATION 17.3 • n=7 Participants	39.5 years STANDARD_DEVIATION 19.2 • n=5 Participants	39.0 years STANDARD_DEVIATION 18.4 • n=4 Participants
Gender Female	86 participants n=5 Participants	68 participants n=7 Participants	163 participants n=5 Participants	317 participants n=4 Participants
Gender Male	284 participants n=5 Participants	286 participants n=7 Participants	438 participants n=5 Participants	1008 participants n=4 Participants
Region of Enrollment United States	291 participants n=5 Participants	259 participants n=7 Participants	441 participants n=5 Participants	991 participants n=4 Participants
Region of Enrollment Canada	82 participants n=5 Participants	96 participants n=7 Participants	162 participants n=5 Participants	340 participants n=4 Participants

PRIMARY outcome

Timeframe: 6 months after injury

Population: The primary analysis was designed as modified intent-to-treat, with all patients who had fluid connected to intravenous (IV) tubing included regardless of how much fluid was administered. Per the a priori trial design, patients for whom the fluid bag was opened but not connected to the IV were not considered enrolled in the trial.

Glasgow outcome score extended (GOSE) contains eight categories: 1. Dead, 2. Vegetative State (VS), 3. Lower Severe Disability (Lower SD), 4. Upper Severe Disability (Upper SD), 5. Lower Moderate Disability (Lower MD), 6. Upper Moderate Disability (Upper MD), 7. Lower Good Recovery (Lower GR) and 8. Upper Good Recovery (Upper GR). A measured neurological outcome of GOSE≤4 is a poor outcome of severe disability, vegetative state, or death. Completer analysis includes only those patients with GOSE completed at 6 months after injury.

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=302 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=293 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=492 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Completer Analysis	181 Participants	171 Participants	276 Participants

PRIMARY outcome

Timeframe: 6 months after injury

Population: To adjust for 15% of subjects with absent 6-month GOSE data, an analysis using 20 hot deck imputations for the 6-month GOSE was done using data from patients who were discharged alive based on 1-month post discharge GOSE data or discharge GOSE (if 1-month post discharge data were not available), length of hospital stay, and treatment group.

Glasgow outcome score extended (GOSE) contains 8 categories: 1. Dead, 2. Vegetative State, 3. Lower Severe Disability, 4. Upper Severe Disability, 5. Lower Moderate Disability, 6. Upper Moderate Disability, 7. Lower Good Recovery and 8. Upper Good Recovery. To adjust for 15% of subjects with absent 6-month GOSE data, an analysis using 20 hot deck imputations for the 6-month GOSE was done using data from patients who were discharged alive based on 1-month post discharge GOSE data or discharge GOSE (if 1-month post discharge data were not available), length of hospital stay, and treatment group.

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=359 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=341 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=582 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Imputed Analysis	192.9 Participants (with imputed values)	185.4 Participants (with imputed values)	299.8 Participants (with imputed values)

SECONDARY outcome

Timeframe: 6 months after injury

Population: To adjust for 15% of subjects with absent 6-month GOSE data, an analysis using 20 hot deck imputations for the 6-month GOSE was done using data from patients who were discharged alive based on 1-month post discharge GOSE data or discharge GOSE (if 1-month post discharge data were not available), length of hospital stay, and treatment group.

The Abbreviated Injury Scale (AIS) ranks injuries on a scale of 1 to 6, with 1 being minor, 2 moderate, 3 serious, 4 severe, 5 critical and 6 an unsurvivable injury. A priori secondary analyses included the subgroup of participants in each intervention group with a head AIS≥4, which is a diagnostic indicator of severe to lethal head injury. Of this subset of participants with AIS≥4, a second subset of participants with a GOSE≤4 at the 6 month follow up was analyzed. GOSE≤4 represents Upper Severe Disability or worse outcomes. 15% of subjects required imputation analysis for 6-month GOSE.

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=208 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=193 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=331 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Subgroup of Participants With Head Abbreviated Injury Scores (AIS) Greater Than or Equal to 4 (Head AIS≥4) Assessed to Have Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Imputed Analysis	146.1 Participants (with imputed values)	128.0 Participants (with imputed values)	219.0 Participants (with imputed values)

SECONDARY outcome

Timeframe: 6 months after injury

Population: To adjust for 15% of subjects with absent 6-month GOSE data, an analysis using 20 hot deck imputations for the 6-month GOSE was done using data from patients who were discharged alive based on 1-month post discharge GOSE data or discharge GOSE (if 1-month post discharge data were not available), length of hospital stay, and treatment group.

The Abbreviated Injury Scale (AIS) ranks injuries on a scale of 1 to 6, with 1 being minor, 2 moderate, 3 serious, 4 severe, 5 critical and 6 an unsurvivable injury. A priori secondary analyses included the subgroup of participants in each intervention group with a head AIS≥2, which is a diagnostic indicator of moderate to lethal head injury. Of this subset of participants with AIS≥2, a second subset of participants with a GOSE≤4 at the 6 month follow up was analyzed. GOSE≤4 represents Upper Severe Disability or worse outcomes. 15% of subjects required imputation analysis for 6-month GOSE.

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=281 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=268 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=458 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Subgroup of Participants With Head Abbreviated Injury Scores (AIS) Greater Than or Equal to 2 (Head AIS≥2) Assessed to Have Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Imputed Analysis	166.7 Participants (with imputed values)	150.6 Participants (with imputed values)	253.2 Participants (with imputed values)

SECONDARY outcome

Timeframe: 6 months after injury

Population: To adjust for 15% of subjects with absent 6-month DRS data, an analysis using 20 hot deck imputations for the 6-month DRS was done using data from patients who were discharged alive based on 1-month post discharge DRS data or discharge DRS (if 1-month post discharge data were not available), length of hospital stay, and treatment group.

The DRS is an additional measure of neurological outcome that categorizes the patient's level of disability on a scale of 0 to 29, with 0 indicating no disability to 29 indicating extreme vegetative state. To adjust for 15% of subjects with absent 6-month DRS data, an analysis using 20 hot deck imputations for the 6-month DRS was done using data from patients who were discharged alive based on 1-month post discharge DRS data or discharge DRS (if 1-month post discharge data were not available), length of hospital stay, and treatment group.

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=359 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=341 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=582 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Disability Rating Score (DRS) Categories of Disability 0-1 (none/mild disability)	124.8 Participants (with imputed values)	128.0 Participants (with imputed values)	232.0 Participants (with imputed values)
Disability Rating Score (DRS) Categories of Disability 2-6 (Partial/Moderate Disability)	98.3 Participants (with imputed values)	89.4 Participants (with imputed values)	143.2 Participants (with imputed values)
Disability Rating Score (DRS) Categories of Disability 7-21 (moderately severe/severe/extremely severe)	33.0 Participants (with imputed values)	26.6 Participants (with imputed values)	43.3 Participants (with imputed values)
Disability Rating Score (DRS) Categories of Disability 22-30 (vegetative/extreme vegetative/dead)	102.9 Participants (with imputed values)	97.0 Participants (with imputed values)	163.4 Participants (with imputed values)

SECONDARY outcome

Timeframe: 28 days after injury

Population: An analysis of this secondary outcome was done for all participants assigned to each of the three groups who did not refuse or were lost to follow-up prior to discharge.

The patient who is admitted to the hospital after injury and is alive on the 28th day after injury. For 28-day survival, patients with missing 28-day vital status who were known to be discharged alive prior to 28 days were assumed to be alive at day 28.

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=357 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=340 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=575 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
28 Day Survival	268 Participants	260 Participants	432 Participants

SECONDARY outcome

Timeframe: Date of hospital discharge up to 6 months from date of injury

Population: An analysis of this secondary outcome was done for all participants assigned to each of the three groups who had relevant data.

The patient who is admitted to the hospital alive after injury and is alive when discharged from the hospital up to 6 months from the date of injury.

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=354 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=337 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=575 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Survival at Hospital Discharge up to 6 Months From Date of Injury	263 Participants	255 Participants	427 Participants

SECONDARY outcome

Timeframe: From day of injury to 28 days after injury

Population: Number of participants analyzed in each group is the actual number analyzed, which does not include participants with one of the following: 1. prehospital death; 2. transfer to another hospital without IRB approval; or 3. patient, family member, or legally authorized representative refused consent and was withdrawn from the study.

The patient is alive and free of ARDS from the date of injury through to the 28th day following injury. The diagnosis of ARDS is based on standard criteria: a) hypoxia with a ratio of arterial oxygen pressure to percent oxygen delivered of less than 200; b) bilateral infiltrates on chest X-ray; and c) clinical evidence of increased left atrial pressure or pulmonary artery wedge pressure of greater than 18 mmHg.

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=356 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=337 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=572 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Acute Respiratory Distress Syndrome (ARDS)-Free Survival to Day 28	247 Participants	239 Participants	401 Participants

SECONDARY outcome

Timeframe: From day of injury to 28 days after injury

Population: Number of participants analyzed in each group is the actual number analyzed, which does not include participants with one of the following: 1. prehospital death; 2. transfer to another hospital without IRB approval; or 3. patient, family member, or legally authorized representative refused consent and was withdrawn from the study.

Multiple Organ Dysfunction Score is described as: Six organ systems were chosen: 1) respiratory; 2) renal; 3) hepatic; 4) cardiovascular; 5) hematologic; and 6) neurologica. A score of 0-4 was allotted for each organ according to function (0 being normal function through 4 for most severe dysfunction) with a maximum score of 24. The worst score based on available data (missing values were assumed normal) was taken for calculation of the aggregate score. Deaths are assigned the worst score (24).

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=348 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=329 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=558 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Worst Multiple Organ Dysfunction Score (MODS) Through Day 28	9 Scores on a scale Standard Deviation 9.3	8.6 Scores on a scale Standard Deviation 9.3	8.6 Scores on a scale Standard Deviation 9.5

SECONDARY outcome

Timeframe: From day of injury to 28 days after injury

Population: Number of participants analyzed in each group is the actual number analyzed, which does not include participants with one of the following: 1. prehospital death; 2. transfer to another hospital without IRB approval; or 3. patient, family member, or legally authorized representative refused consent and was withdrawn from the study.

The number of days beginning with the day of 911 call counted as "Day 0" through day 28 that the patient did not require mechanical ventilation. Deaths are assigned the worst score (0).

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=355 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=337 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=572 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Ventilator-free Days Through Day 28	17.0 Days Standard Deviation 11.6	17.6 Days Standard Deviation 11.5	17.4 Days Standard Deviation 11.7

SECONDARY outcome

Timeframe: From day of injury to 28 days after injury

Population: Number of participants analyzed in each group is the actual number analyzed, which does not include participants with one of the following: 1. prehospital death; 2. transfer to another hospital without IRB approval; or 3. patient, family member, or legally authorized representative refused consent and was withdrawn from the study.

The number of days the patient is alive and not being cared for in the intensive care unit

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=355 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=337 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=572 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Days Alive Out of the Intensive Care Unit (ICU) Through Day 28	15.2 Days Standard Deviation 11.5	15.8 Days Standard Deviation 11.4	15.6 Days Standard Deviation 11.7

SECONDARY outcome

Timeframe: From day of injury to 28 days after injury

Population: Number of participants analyzed in each group is the actual number analyzed, which does not include participants with one of the following: 1. prehospital death; 2. transfer to another hospital without IRB approval; or 3. patient, family member, or legally authorized representative refused consent and was withdrawn from the study.

The number of days the patient is alive and no longer an inpatient in the hospital through day 28

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=354 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=337 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=575 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Days Alive Out of the Hospital Through Day 28	9.8 Days Standard Deviation 10.9	10 Days Standard Deviation 11.0	10.7 Days Standard Deviation 11.2

SECONDARY outcome

Timeframe: From day of injury to 28 days after injury

Population: An analysis of this secondary outcome was done for all participants assigned to each of the three groups who had relevant data. Percentages were based on population at risk. Row 1 nosocomial infections; Row 2 pneumonia; Row 3 bloodstream infections; Row 4 urinary tract infections; and Row 5 wound infections

Includes one or more nosocomial infections diagnosed during the hospital stay but not present on admission to the hospital from the following list: pneumonia, bloodstream infection, urinary tract infection, and/or wound infection

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=320 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=313 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=530 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Presence of Nosocomial Infections Nosocomial Infections ≥ 1	102 Diagnoses	101 Diagnoses	136 Diagnoses
Presence of Nosocomial Infections Pneumonia	72 Diagnoses	71 Diagnoses	100 Diagnoses
Presence of Nosocomial Infections Bloodstream Infection	23 Diagnoses	21 Diagnoses	19 Diagnoses
Presence of Nosocomial Infections Urinary Tract Infection	30 Diagnoses	32 Diagnoses	32 Diagnoses
Presence of Nosocomial Infections Wound Infection	8 Diagnoses	8 Diagnoses	16 Diagnoses

SECONDARY outcome

Timeframe: First 24 hours from the time dispatch received 911 call

Population: An analysis of this secondary outcome was done for all participants assigned to each of the three groups who had relevant data.

The average (mean) total amount of intravenous (IV) fluids given in the pre-hospital setting and the hospital setting in the first 24 hours following the time of the 911 call

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=357 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=341 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=581 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Total Fluids in First 24 Hours	6.7 Liters Standard Deviation 5.5	6.7 Liters Standard Deviation 5.5	6.9 Liters Standard Deviation 5.7

SECONDARY outcome

Timeframe: First 24 hours from the time dispatch received 911 call

Population: An analysis of this secondary outcome was done for all participants assigned to each of the three groups who had relevant data.

The average (mean) number of units of packed red blood cells (PRBC) transfused in the first 24 hours following the time of the 911 call in each group.

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=356 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=341 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=580 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Packed Red Blood Cells (PRBC) First 24 Hours	1.4 Unit of PRBC Standard Deviation 3.6	1.2 Unit of PRBC Standard Deviation 3.4	1.5 Unit of PRBC Standard Deviation 4.3

SECONDARY outcome

Timeframe: Duration of hospital stay

Population: Number of participants analyzed in each group is the actual number analyzed, which does not include participants with one of the following: 1. prehospital death; 2. transfer to another hospital without IRB approval; or 3. patient, family member, or legally authorized representative refused consent and was withdrawn from the study.

Disposition of patient at the time of discharge from the acute care hospital

Outcome measures

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=352 Participants 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=336 Participants 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=574 Participants 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Discharge Disposition Home	138 Participants	134 Participants	253 Participants
Discharge Disposition Death	89 Participants	81 Participants	147 Participants
Discharge Disposition Inpatient Rehabilitation	84 Participants	90 Participants	122 Participants
Discharge Disposition Skilled Nursing Facility	37 Participants	28 Participants	40 Participants
Discharge Disposition Nursing Home or Inpatient Psychiatric Facility	4 Participants	3 Participants	12 Participants

Adverse Events

7.5% Hypertonic Saline/6% Dextran (HSD)

Serious events: 69 serious events

Other events: 0 other events

Deaths: 0 deaths

7.5% Hypertonic Saline (HS)

Serious events: 72 serious events

Other events: 0 other events

Deaths: 0 deaths

0.9% Normal Saline (NS)

Serious events: 141 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	7.5% Hypertonic Saline/6% Dextran (HSD) n=359 participants at risk 250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	7.5% Hypertonic Saline (HS) n=341 participants at risk 250 ml intravenous bolus administration of 7.5% hypertonic saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.	0.9% Normal Saline (NS) n=582 participants at risk 250 ml intravenous bolus administration of 0.9% saline as the initial resuscitation fluid given to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.
Blood and lymphatic system disorders Hypernatremia (sodium>160 mEq/L) requiring intervention	2.9% 10/349 • Number of events 10 • The time frame was from May 2006 through May 2009, which was 3 years Serial blood sodium levels were drawn to monitor the effects of the hypertonic saline solutions; Serial head CT's (computed tomography) were done to monitor for increased intracranial hemorrhage; and incidents of seizures in the first 24 hours.	4.2% 14/334 • Number of events 14 • The time frame was from May 2006 through May 2009, which was 3 years Serial blood sodium levels were drawn to monitor the effects of the hypertonic saline solutions; Serial head CT's (computed tomography) were done to monitor for increased intracranial hemorrhage; and incidents of seizures in the first 24 hours.	2.3% 13/573 • Number of events 13 • The time frame was from May 2006 through May 2009, which was 3 years Serial blood sodium levels were drawn to monitor the effects of the hypertonic saline solutions; Serial head CT's (computed tomography) were done to monitor for increased intracranial hemorrhage; and incidents of seizures in the first 24 hours.
Nervous system disorders Increased intracranial hemorrhage on serial head CT	16.3% 57/349 • Number of events 57 • The time frame was from May 2006 through May 2009, which was 3 years Serial blood sodium levels were drawn to monitor the effects of the hypertonic saline solutions; Serial head CT's (computed tomography) were done to monitor for increased intracranial hemorrhage; and incidents of seizures in the first 24 hours.	18.5% 60/325 • Number of events 60 • The time frame was from May 2006 through May 2009, which was 3 years Serial blood sodium levels were drawn to monitor the effects of the hypertonic saline solutions; Serial head CT's (computed tomography) were done to monitor for increased intracranial hemorrhage; and incidents of seizures in the first 24 hours.	21.8% 122/560 • Number of events 122 • The time frame was from May 2006 through May 2009, which was 3 years Serial blood sodium levels were drawn to monitor the effects of the hypertonic saline solutions; Serial head CT's (computed tomography) were done to monitor for increased intracranial hemorrhage; and incidents of seizures in the first 24 hours.
Nervous system disorders Seizures in the first 24 hours	1.1% 4/359 • Number of events 4 • The time frame was from May 2006 through May 2009, which was 3 years Serial blood sodium levels were drawn to monitor the effects of the hypertonic saline solutions; Serial head CT's (computed tomography) were done to monitor for increased intracranial hemorrhage; and incidents of seizures in the first 24 hours.	0.88% 3/341 • Number of events 3 • The time frame was from May 2006 through May 2009, which was 3 years Serial blood sodium levels were drawn to monitor the effects of the hypertonic saline solutions; Serial head CT's (computed tomography) were done to monitor for increased intracranial hemorrhage; and incidents of seizures in the first 24 hours.	2.1% 12/582 • Number of events 12 • The time frame was from May 2006 through May 2009, which was 3 years Serial blood sodium levels were drawn to monitor the effects of the hypertonic saline solutions; Serial head CT's (computed tomography) were done to monitor for increased intracranial hemorrhage; and incidents of seizures in the first 24 hours.

Other adverse events

Adverse event data not reported

Additional Information

Susanne May, PhD

Clinical Trial Center, University of Washington, Seattle, WA

Phone: 206-685-1302

Email: sjmay@uw.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place