Clinical trial NCT00316004: Hypertonic Resuscitation Following Severe Traumatic Brain Injury (TBI)
Official title: Phase 3 Study of Hypertonic Resuscitation Following Severe Traumatic Brain Injury (TBI)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Brain Injuries, Traumatic
Keywords: Traumatic
Brain injury
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: U.S. Army Medical Research and Development Command
name: Canadian Institutes of Health Research (CIHR)
name: Canadian Department of National Defense
name: Heart and Stroke Foundation of Canada
First posted: 2006-04-19
Enrollment: 1331
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if hypertonic saline with and without dextran can improve neurologic outcomes in victims of severe traumatic brain injury (TBI).

Injury and lost blood from trauma can cause your body to go into shock (low blood pressure related to blood loss). This decreased blood flow can lead to organ damage. In order to restore the blood pressure and blood flow, the medics give fluids into the patients' veins as soon as possible. This is called "resuscitation". The fluid most commonly used is "isotonic" or one that is the same salt concentration as the blood. The investigators are trying to determine if infusing a "hypertonic" fluid or one more concentrated than the blood can increase the blood pressure and restore blood flow more efficiently. The hypertonic fluids they are using are called hypertonic saline with dextran (HSD) and hypertonic saline (no dextran). Hypertonic saline is a salt solution that is slightly more concentrated than blood. Dextran is a sugar solution.

Detailed description: To determine if prehospital administration of 7.5% Hypertonic Saline in 6% Dextran-70 (HSD) OR 7.5% Hypertonic Saline (HS) compared to current standard therapy with NS as an initial resuscitation fluid affects neurological outcome following severe traumatic brain injury.

Trauma is the leading cause of death among North Americans between the ages of 1 and 44 years. The majority of these deaths result from hypovolemic shock or severe brain injury. Patients in hypovolemic shock develop a state of systemic tissue ischemia then a subsequent reperfusion injury at the time of fluid resuscitation. Conventional resuscitation involves the IV administration of a large volume of isotonic or slightly hypotonic (lactated ringers, LR) solutions beginning in the pre-hospital setting. Although not conclusive, prior studies have suggested that alternative resuscitation with hypertonic saline (7.5%) solutions may reduce morbidity or mortality in these patients. Furthermore, hypertonic fluids may have specific advantages in the brain-injured patient, as they may aid in the rapid restoration of cerebral perfusion and prevent extravascular fluid sequestration, thereby limiting secondary brain injury. In addition, recent studies have demonstrated that hypertonicity significantly alters the activation of inflammatory cells, an effect that may reduce subsequent organ injury from ischemia-reperfusion and decrease nosocomial infection.

This study is a randomized, double-blind, three-arm placebo controlled trial designed to evaluate the clinical outcome of trauma patients with severe TBI as manifested by a pre-hospital GCS of 8 or less. Patients will be randomized to a single 250cc IV dose of 7.5% saline in 6% Dextran-70 (HSD), 7.5% saline (HS) or normal saline as the initial fluid for pre-hospital resuscitation. No additional interventions will occur once the patient is admitted to the hospital. In hospital data collection will last up to 28 days. Patients will have neurologic outcome measurements at discharge, 1 month post discharge, and 6 months post injury. Enrollment will be restricted to age ≥ 15 years or ≥ 50 kg if age is unknown.

Eligibility criteria: Inclusion Criteria:

* Blunt trauma
* Pre-hospital Glasgow Coma Scale equal to or less than 8(GCS≤8)\*
* Age 15 years or older or 50 kg or more

  * Patients who met the inclusion criteria above and did not meet the exclusion criteria below but who had systolic blood pressure (SBP) ≤70 or SBP\>70 and SBP≤90 and heart rate (HR)≥108 were included in the Hypertonic Resuscitation following Traumatic Injury study that focused on shock patients who may or may not have a traumatic brain injury (TBI). In other words, patients with both TBI and shock would not be included in this study of TBI patients without shock at the time of enrollment.

Exclusion Criteria:

* Known or suspected pregnancy
* Age younger than 15 years or less than 50 kg if age unknown
* Ongoing pre-hospital cardiopulmonary resuscitation (CPR)
* Administration of more than 2L crystalloid or any colloid or blood products
* Severe hypothermia (T less than 28C)
* Drowning or asphyxia due to hanging
* Burns TBSA more than 20%
* Isolated penetrating injury to the head
* Inability to obtain pre-hospital intravenous access
* Time of call received at dispatch to study intervention more than four hours
* Known prisoners

Primary outcomes:
measure: Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Completer Analysis
timeFrame: 6 months after injury
measure: Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Imputed Analysis
timeFrame: 6 months after injury
Secondary outcomes:
measure: 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
timeFrame: 6 months after injury
measure: 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
timeFrame: 6 months after injury
measure: Disability Rating Score (DRS) Categories of Disability
timeFrame: 6 months after injury
measure: 28 Day Survival
timeFrame: 28 days after injury
measure: Survival at Hospital Discharge up to 6 Months From Date of Injury
timeFrame: Date of hospital discharge up to 6 months from date of injury
measure: Acute Respiratory Distress Syndrome (ARDS)-Free Survival to Day 28
timeFrame: From day of injury to 28 days after injury
measure: Worst Multiple Organ Dysfunction Score (MODS) Through Day 28
timeFrame: From day of injury to 28 days after injury
measure: Ventilator-free Days Through Day 28
timeFrame: From day of injury to 28 days after injury
measure: Days Alive Out of the Intensive Care Unit (ICU) Through Day 28
timeFrame: From day of injury to 28 days after injury
measure: Days Alive Out of the Hospital Through Day 28
timeFrame: From day of injury to 28 days after injury
measure: Presence of Nosocomial Infections
timeFrame: From day of injury to 28 days after injury
measure: Total Fluids in First 24 Hours
timeFrame: First 24 hours from the time dispatch received 911 call
measure: Packed Red Blood Cells (PRBC) First 24 Hours
timeFrame: First 24 hours from the time dispatch received 911 call
measure: Discharge Disposition
timeFrame: Duration of hospital stay
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Resuscitation Center, University of Alabama
state: Alabama
city: Orange
country: United States
facility: Orange County/UC Irvine
state: California
city: San Diego
country: United States
facility: UCSD-San Diego Resuscitation Research Center
state: California
city: Iowa City
country: United States
facility: Iowa Resuscitation Network, University of Iowa Carver College of Medicine
state: Iowa
city: Portland
country: United States
facility: Portland Resuscitation Outcomes Consortium, Oregon Health & Sciences University
state: Oregon
city: Pittsburgh
country: United States
facility: The Pittsburgh Resuscitation Network, University of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: The Regional Medical Center at Memphis
state: Tennessee
city: Dallas
country: United States
facility: Dallas Center for Resuscitation Research, University of Texas Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: Seattle-King County Center for Resuscitation Research, University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Milwaukee Resuscitation Network, Medical College of Wisconsin
state: Wisconsin
city: Ottawa
country: Canada
facility: University of Ottawa/University of British Columbia Collaborative RCC, Ottawa Health Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Toronto Regional Resuscitation Research Out-of-Hospital Network, University of Toronto
state: Ontario
Study officials:
affiliation: Resuscitation Outcomes Consortium
name: Myron L Weisfeldt, MD
role: STUDY_CHAIR
References:
citation: Bulger EM, May S, Brasel KJ, Schreiber M, Kerby JD, Tisherman SA, Newgard C, Slutsky A, Coimbra R, Emerson S, Minei JP, Bardarson B, Kudenchuk P, Baker A, Christenson J, Idris A, Davis D, Fabian TC, Aufderheide TP, Callaway C, Williams C, Banek J, Vaillancourt C, van Heest R, Sopko G, Hata JS, Hoyt DB; ROC Investigators. Out-of-hospital hypertonic resuscitation following severe traumatic brain injury: a randomized controlled trial. JAMA. 2010 Oct 6;304(13):1455-64. doi: 10.1001/jama.2010.1405.
citation: Tisherman SA, Schmicker RH, Brasel KJ, Bulger EM, Kerby JD, Minei JP, Powell JL, Reiff DA, Rizoli SB, Schreiber MA. Detailed description of all deaths in both the shock and traumatic brain injury hypertonic saline trials of the Resuscitation Outcomes Consortium. Ann Surg. 2015 Mar;261(3):586-90. doi: 10.1097/SLA.0000000000000837.