Hypertonic Resuscitation Following Traumatic Injury

NCT ID: NCT00316017

Last Updated: 2011-03-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 895 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2009-08-31

Brief Summary

The purpose of this study is to determine if hypertonic saline with and without dextran can improve overall survival in victims of trauma with shock.

Injury and lost blood from trauma can cause your body to be in 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 resuscitation fluid most commonly used is "isotonic" or one that is the same 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 the investigators 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 your blood. Dextran is a sugar solution.

Detailed Description

Specific Aim: To determine if prehospital administration of 7.5% hypertonic saline /6% Dextran-70 (HSD) OR 7.5% hypertonic saline alone (HS), compared to current standard therapy with normal saline (NS), as an initial resuscitation fluid, affects survival following traumatic injury with hypovolemic shock.

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 prehospital 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. The majority of previous clinical trials have focused on the use of HSD. The potential for 7.5% saline alone (HS) to have similar effects has not been well studied. Removal of the dextran component may enhance the anti-inflammatory effects of this solution, which could improve secondary outcomes such as acute respiratory distress syndrome (ARDS), multiple organ failure syndrome (MOFS) and rates of nosocomial infections.

This study is a randomized, double-blind, three-arm placebo controlled trial designed to evaluate the clinical outcome of trauma patients with hypovolemic shock, as manifested by prehospital hypotension. 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 prehospital resuscitation. No additional interventions will occur once the patient is admitted to the hospital. In hospital data collection will last up to 28 days.

Conditions

Shock, Traumatic

Study Design

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

Study Groups

1

7.5% hypertonic saline/6% Dextran-70 (HSD)

Group Type: EXPERIMENTAL

7.5% hypertonic saline/6% Dextran-70 (HSD)

Intervention Type: DRUG

250 cc dose given as a one-time intravenous (IV) bolus in the pre-hospital setting.

2

7.5% hypertonic saline (HS)

Group Type: EXPERIMENTAL

7.5% hypertonic saline (HS)

Intervention Type: DRUG

250 cc dose given as a one-time IV bolus in the pre-hospital setting.

3

0.9% normal saline

Group Type: PLACEBO_COMPARATOR

0.9% normal saline

Intervention Type: DRUG

250 cc dose given as a one-time IV bolus in the pre-hospital setting.

Interventions

7.5% hypertonic saline/6% Dextran-70 (HSD)

250 cc dose given as a one-time intravenous (IV) bolus in the pre-hospital setting.

Intervention Type: DRUG

7.5% hypertonic saline (HS)

250 cc dose given as a one-time IV bolus in the pre-hospital setting.

Intervention Type: DRUG

0.9% normal saline

250 cc dose given as a one-time IV bolus in the pre-hospital setting.

Intervention Type: DRUG

Other Intervention Names

RescueFlo

Eligibility Criteria

Inclusion Criteria

• Blunt or penetrating trauma
• Prehospital Systolic Blood Pressure (SBP) <= 70;OR
• Prehospital SBP 71-90 AND Hear Rate (HR) ≥108
• 15 years of age or older, or 50kg or more if age unknown

Exclusion Criteria

• Known or suspected pregnancy
• Age younger than 15 or less than 50kg if age unknown
• Ongoing prehospital cardiopulmonary resuscitation (CPR)
• Administration of more than 2000cc crystalloid or any colloid or blood products
• Severe hypothermia (suspected Temperature less than 28 degrees celsius)
• Drowning or asphyxia due to hanging
• Burns Total Body Surface Area (TBSA) more than 20%
• Isolated penetrating injury to the head
• Inability to obtain prehospital intravenous access
• Time of call received at dispatch to study intervention greater 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

The Institute of Circulatory and Respiratory Health (ICRH)

UNKNOWN

Sponsor Role: collaborator

Defence Research and Development Canada

INDUSTRY

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 Resuscitaion Center, University of Alabama

Birmingham, Alabama, 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

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, Kerby JD, Emerson S, Stiell IG, Schreiber MA, Brasel KJ, Tisherman SA, Coimbra R, Rizoli S, Minei JP, Hata JS, Sopko G, Evans DC, Hoyt DB; ROC investigators. Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial. Ann Surg. 2011 Mar;253(3):431-41. doi: 10.1097/SLA.0b013e3181fcdb22.

Reference Type: RESULT

PMID: 21178763 (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 #12506 (shock cohort)

Identifier Type: OTHER

Identifier Source: secondary_id

28226-A - IND 12506

Identifier Type: -

Identifier Source: org_study_id