Hypertonic Resuscitation Following Severe Traumatic Brain Injury (TBI)

NCT ID: NCT00316004

Last Updated: 2011-05-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1331 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2010-01-31

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.

Conditions

Brain Injuries, Traumatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

7.5% hypertonic saline/6% dextran (HSD)

250 ml intravenous bolus administration of 7.5% saline/6% dextran 70

Group Type: EXPERIMENTAL

7.5% Hypertonic Saline in 6% Dextran-70 (HSD)

Intervention Type: DRUG

250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 administered as a one-time bolus fluid for initial resuscitation 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

Group Type: EXPERIMENTAL

7.5% Hypertonic Saline (HS)

Intervention Type: DRUG

250 ml intravenous bolus administration of 7.5% hypertonic saline administered as a one-time bolus fluid for initial resuscitation 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

Group Type: PLACEBO_COMPARATOR

0.9% Normal Saline (NS)

Intervention Type: DRUG

250 ml intravenous bolus administration of 0.9% saline administered as a one-time bolus fluid for initial resuscitation to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.

Interventions

7.5% Hypertonic Saline in 6% Dextran-70 (HSD)

250 ml intravenous bolus administration of 7.5% saline/6% dextran 70 administered as a one-time bolus fluid for initial resuscitation to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.

Intervention Type: DRUG

7.5% Hypertonic Saline (HS)

250 ml intravenous bolus administration of 7.5% hypertonic saline administered as a one-time bolus fluid for initial resuscitation to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.

Intervention Type: DRUG

0.9% Normal Saline (NS)

250 ml intravenous bolus administration of 0.9% saline administered as a one-time bolus fluid for initial resuscitation to injured patients with suspected severe traumatic brain injury in the out-of-hospital setting.

Intervention Type: DRUG

Other Intervention Names

RescueFlo

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

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

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

U.S. Army Medical Research and Development Command

FED

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Canadian Department of National Defense

OTHER_GOV

Sponsor Role: collaborator

Heart and Stroke Foundation of Canada

OTHER

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Resuscitation Outcomes Consortium Data Coordinating Center

Principal Investigators

Myron L Weisfeldt, MD

Role: STUDY_CHAIR

Resuscitation Outcomes Consortium

Locations

Alabama Resuscitation Center, University of Alabama

Birmingham, Alabama, United States

Orange County/UC Irvine

Orange, California, United States

UCSD-San Diego Resuscitation Research Center

San Diego, California, United States

Iowa Resuscitation Network, University of Iowa Carver College of Medicine

Iowa City, Iowa, United States

Portland Resuscitation Outcomes Consortium, Oregon Health & Sciences University

Portland, Oregon, United States

The Pittsburgh Resuscitation Network, University of Pittsburgh

Pittsburgh, Pennsylvania, United States

The Regional Medical Center at Memphis

Memphis, Tennessee, United States

Dallas Center for Resuscitation Research, University of Texas Southwestern Medical Center

Dallas, Texas, United States

Seattle-King County Center for Resuscitation Research, University of Washington

Seattle, Washington, United States

Milwaukee Resuscitation Network, Medical College of Wisconsin

Milwaukee, Wisconsin, United States

University of Ottawa/University of British Columbia Collaborative RCC, Ottawa Health Research Institute

Ottawa, Ontario, Canada

Toronto Regional Resuscitation Research Out-of-Hospital Network, University of Toronto

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: RESULT

PMID: 20924011 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25072443 (View on PubMed)

Other Identifiers

5U01HL077863-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IND #12505 TBI cohort

Identifier Type: OTHER

Identifier Source: secondary_id

28226-A - IND 12505

Identifier Type: -

Identifier Source: org_study_id