Hypertonic Resuscitation Following Traumatic Injury

This study has been terminated.
(Futility & potential safety concern (increased early mortality in the HS/HSD arms for those with no PRBC in 1st 24 hr, post-randomization subgp))
Sponsor:
Collaborators:
The Institute of Circulatory and Respiratory Health (ICRH)
Defence Research and Development Canada
Information provided by:
University of Washington
ClinicalTrials.gov Identifier:
NCT00316017
First received: April 17, 2006
Last updated: February 25, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention Phase
Shock, Traumatic
Drug: 7.5% hypertonic saline/6% Dextran-70 (HSD)
Drug: 7.5% hypertonic saline (HS)
Drug: 0.9% normal saline
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 3 Study of Hypertonic Resuscitation Following Traumatic Injury With Hypovolemic Shock

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • 28 Day Survival [ Time Frame: 28 days from time of Emergency Department (ED) arrival ] [ Designated as safety issue: No ]
    The day of episode is counted as "Day 0". So for measures using a 28 day period, the maximum value is 29 (i.e. days 0 through 28).


Secondary Outcome Measures:
  • Adult Respiratory Distress Syndrome(ARDS)-Free Survival Through Day 28 [ Time Frame: 28 days from time of ED arrival ] [ Designated as safety issue: No ]
    Absence of diagnosis of Adult Respiratory Distress Syndrome and alive through day 28

  • Worst Multiple Organ Dysfunction Score (MODS) Mean Through Day 28 [ Time Frame: 28 days from time of ED arrival ] [ Designated as safety issue: No ]

    Multiple Organ Dysfunction Score is described as:

    Six organ systems were chosen, and a score of 0-4 allotted for each organ according to function (0 being normal function through to 4 for most severe dysfunction) with a maximum score of 24. The worst score based on available data (missing values were assumed normal) in each 24-hour period is taken for calculation of the aggregate score.


  • Presence of Nosocomial Infection Through Day 28 [ Time Frame: Within 28 days of injury, while hospitalized ] [ Designated as safety issue: No ]
    Includes one or more nosocomial infections from the following list: pneumonia, blood stream infection, urinary tract infection and wound infection

  • Packed Red Blood Cells (PRBC) First 24 Hours [ Time Frame: First 24 hours from the time of 911 call ] [ Designated as safety issue: No ]
    The numbers of units of packed red blood cells transfused in the first 24 hours

  • Total Fluids First 24 Hours [ Time Frame: First 24 hours from the time of of 911 call ] [ Designated as safety issue: No ]
    The total amount of IV fluids given in the pre-hospital setting and the hospital setting in the first 24 hours following the time of 911 call

  • Ventilator-free Days Through Day 28 [ Time Frame: Duration of hospital stay through day 28 ] [ Designated as safety issue: No ]
    The number of days beginning with the day of 911 call counted as "Day O" through day 28 that the patient did not require mechanical ventilation

  • Days Alive Out of the Intensive Care Unit (ICU) Through Day 28 [ Time Frame: First 28 days from the time of 911 call ] [ Designated as safety issue: No ]
    The number of days the patient is alive and not being cared for in the intensive care unit

  • Days Alive Out of the Hospital Through Day 28 [ Time Frame: First 28 days from the time of 911 call ] [ Designated as safety issue: No ]
    The number of days the patient is alive and no longer an inpatient in the hospital through day 28

  • Survival at Hospital Discharge [ Time Frame: Duration of hospital stay through to discharge ] [ Designated as safety issue: No ]
    Alive at the time of discharge from the Level One or Two trauma hospital. This did not include disposition from rehabilitation facilities.

  • Zero Units PRBC in First 24 Hours [ Time Frame: From the time dispatch received the 911 call to the end of the first 24 hours ] [ Designated as safety issue: No ]
    This is the total number of subjects who received no blood products in the first 24 hours from the time of the 911 call.

  • Zero Units PRBC and Died in Field or Emergency Department (ED) [ Time Frame: From the time dispatch received 911 call to the time of death in the field or ED ] [ Designated as safety issue: Yes ]
    This is the total number of subjects who died in the field or the ED from the set of subjects who received no blood products.

  • Zero Units PRBC and Died Within 6 Hours of Admission to the Hospital [ Time Frame: The first 6 hours from the time of admission to the hospital ] [ Designated as safety issue: Yes ]
    This is the total number of subjects who died within the first 6 hours from the time of admission to the hospital among the patients who received no blood products.

  • Zero Units PRBC and Died Within 28 Days From the Time of the 911 Call [ Time Frame: From the time dispatch received the 911 call to 28 days ] [ Designated as safety issue: Yes ]
    This is the total number of subjects who died within 28 days from the time of the 911 call among the patients who received no units of PRBC.

  • 1-9 Units PRBC in First 24 Hours [ Time Frame: From the time dispatch received the 911 call to the end of the first 24 hours ] [ Designated as safety issue: No ]
    This is the total number of subjects who received 1 to 9 units of packed red blood cells (PRBC) in the first 24 hours from the time of the 911 call.

  • 1-9 Units PRBC and Died in Field or ED [ Time Frame: From the time dispatch received 911 call to the time of death in the field or ED ] [ Designated as safety issue: No ]
    This is the total number of subjects who received 1 to 9 units of packed red blood cells (PRBC) among the patients who died in the field or the ED.

  • 1-9 Units PRBC and Died Within 6 Hours of Admission to the Hospital [ Time Frame: The first 6 hours from the time of admission to the hospital ] [ Designated as safety issue: No ]
    This is the total number of subjects who died within the first 6 hours from the time of admission to the hospital among the patients who received 1 to 9 units of packed red blood cells (PRBC).

  • 1-9 Units PRBC and Died Within 28 Days From the Time of the 911 Call [ Time Frame: From the time dispatch received the 911 call to 28 days ] [ Designated as safety issue: No ]
    This is the total number of subjects who died within 28 days from the time of the 911 call among the patients who received 1 to 9 units of packed red blood cells (PRBC).

  • Greater Than 10 Units PRBC in First 24 Hours [ Time Frame: From the time dispatch received the 911 call to the end of the first 24 hours ] [ Designated as safety issue: No ]
    This is the total number of subjects who received greater than 10 units of packed red blood cells (PRBC) in the first 24 hours from the time of the 911 call.

  • Greater Than 10 Units PRBC and Died in Field or ED [ Time Frame: From the time dispatch received 911 call to the time of death in the field or ED ] [ Designated as safety issue: No ]
    This is the total number of subjects who died in the field or the ED among the patients who received greater than 10 units of packed red blood cells (PRBC).

  • Greater Than 10 Units PRBC and Died Within 6 Hours of Admission to the Hospital [ Time Frame: The first 6 hours from the time of admission to the hospital ] [ Designated as safety issue: No ]
    This is the total number of subjects who died within the first 6 hours from the time of admission to the hospital among the patients who received greater than 10 units of packed red blood cells (PRBC).

  • Greater Than 10 Units PRBC and Died Within 28 Days From the Time of the 911 Call [ Time Frame: From the time dispatch received the 911 call to 28 days ] [ Designated as safety issue: No ]
    This is the total number of subjects who died within 28 days from the time of the 911 call among the patients who received greater than 10 units of packed red blood cells (PRBC).


Enrollment: 895
Study Start Date: May 2006
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
7.5% hypertonic saline/6% Dextran-70 (HSD)
Drug: 7.5% hypertonic saline/6% Dextran-70 (HSD)
250 cc dose given as a one-time intravenous (IV) bolus in the pre-hospital setting.
Other Name: RescueFlo
Experimental: 2
7.5% hypertonic saline (HS)
Drug: 7.5% hypertonic saline (HS)
250 cc dose given as a one-time IV bolus in the pre-hospital setting.
Placebo Comparator: 3
0.9% normal saline
Drug: 0.9% normal saline
250 cc dose given as a one-time IV bolus in the pre-hospital setting.

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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00316017

Locations
United States, Alabama
Alabama Resuscitaion Center, University of Alabama
Birmingham, Alabama, United States, 35249
United States, California
UCSD-San Diego Resuscitation Research Center
San Diego, California, United States, 92103
United States, Iowa
Iowa Resuscitation Network, University of Iowa Carver College of Medicine
Iowa City, Iowa, United States, 52242
United States, Oregon
Portland Resuscitation Outcomes Consortium, Oregon Health & Sciences University
Portland, Oregon, United States, 97239
United States, Pennsylvania
The Pittsburgh Resuscitation Network, University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Dallas Center for Resuscitation Research, University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Washington
Seattle-King County Center For Resuscitation Research, University of Washington
Seattle, Washington, United States, 98195
United States, Wisconsin
Milwaukee Resuscitation Network, Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
University of Ottawa/University of British Columbia Collaborative RCC, Ottawa Health Research Institute
Ottawa, Ontario, Canada, K1Y4E9
Toronto Regional Resuscitation Research Out-of-Hospital Network, University of Toronto
Toronto, Ontario, Canada, M5B1W8
Sponsors and Collaborators
University of Washington
The Institute of Circulatory and Respiratory Health (ICRH)
Defence Research and Development Canada
Investigators
Study Chair: Myron L Weisfeldt, MD Resuscitation Outcomes Consortium
  More Information

Additional Information:
Publications:
Responsible Party: Gerald van Belle, PhD/Prinicipal Investigator, Resuscitation Outcomes Consortium Data Coordinating Center
ClinicalTrials.gov Identifier: NCT00316017     History of Changes
Other Study ID Numbers: 28226-A - IND 12506, 5U01HL077863-05, IND #12506 (shock cohort)
Study First Received: April 17, 2006
Results First Received: September 2, 2010
Last Updated: February 25, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by University of Washington:
Trauma
Shock

Additional relevant MeSH terms:
Shock
Shock, Traumatic
Wounds and Injuries
Pathologic Processes
Dextrans
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Plasma Substitutes
Blood Substitutes

ClinicalTrials.gov processed this record on July 20, 2014