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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

April 17, 2006
February 25, 2011
May 2006
August 2009   (final data collection date for primary outcome measure)
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).
28 day survival
Complete list of historical versions of study NCT00316017 on ClinicalTrials.gov Archive Site
  • 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).
  • ARDS criteria met during the first 28 days post injury
  • Multiple Organ Dysfunction Score (MODS)
  • Presence of nosocomial infection
  • Total fluid requirements in the first 24 hours after injury
  • Number of days on ventilator
  • Duration of hospital stay
Not Provided
Not Provided
 
Hypertonic Resuscitation Following Traumatic Injury
Phase 3 Study of Hypertonic Resuscitation Following Traumatic Injury With Hypovolemic Shock

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Shock, Traumatic
  • 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
  • Drug: 7.5% hypertonic saline (HS)
    250 cc dose given as a one-time IV bolus in the pre-hospital setting.
  • Drug: 0.9% normal saline
    250 cc dose given as a one-time IV bolus in the pre-hospital setting.
  • Experimental: 1
    7.5% hypertonic saline/6% Dextran-70 (HSD)
    Intervention: Drug: 7.5% hypertonic saline/6% Dextran-70 (HSD)
  • Experimental: 2
    7.5% hypertonic saline (HS)
    Intervention: Drug: 7.5% hypertonic saline (HS)
  • Placebo Comparator: 3
    0.9% normal saline
    Intervention: Drug: 0.9% normal saline
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
895
August 2009
August 2009   (final data collection date for primary outcome measure)

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
Both
15 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00316017
28226-A - IND 12506, 5U01HL077863-05, IND #12506 (shock cohort)
Yes
Gerald van Belle, PhD/Prinicipal Investigator, Resuscitation Outcomes Consortium Data Coordinating Center
University of Washington
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • The Institute of Circulatory and Respiratory Health (ICRH)
  • Defence Research and Development Canada
Study Chair: Myron L Weisfeldt, MD Resuscitation Outcomes Consortium
University of Washington
February 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP