Clinical trial NCT00316017: Hypertonic Resuscitation Following Traumatic Injury
Official title: Phase 3 Study of Hypertonic Resuscitation Following Traumatic Injury With Hypovolemic Shock
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Shock, Traumatic
Keywords: Trauma
Shock
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: The Institute of Circulatory and Respiratory Health (ICRH)
name: Defence Research and Development Canada
First posted: 2006-04-19
Enrollment: 895
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 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.

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

Primary outcomes:
measure: 28 Day Survival
timeFrame: 28 days from time of Emergency Department (ED) arrival
Secondary outcomes:
measure: Adult Respiratory Distress Syndrome(ARDS)-Free Survival Through Day 28
timeFrame: 28 days from time of ED arrival
measure: Worst Multiple Organ Dysfunction Score (MODS) Mean Through Day 28
timeFrame: 28 days from time of ED arrival
measure: Presence of Nosocomial Infection Through Day 28
timeFrame: Within 28 days of injury, while hospitalized
measure: Packed Red Blood Cells (PRBC) First 24 Hours
timeFrame: First 24 hours from the time of 911 call
measure: Total Fluids First 24 Hours
timeFrame: First 24 hours from the time of of 911 call
measure: Ventilator-free Days Through Day 28
timeFrame: Duration of hospital stay through day 28
measure: Days Alive Out of the Intensive Care Unit (ICU) Through Day 28
timeFrame: First 28 days from the time of 911 call
measure: Days Alive Out of the Hospital Through Day 28
timeFrame: First 28 days from the time of 911 call
measure: Survival at Hospital Discharge
timeFrame: Duration of hospital stay through to discharge
measure: Zero Units PRBC in First 24 Hours
timeFrame: From the time dispatch received the 911 call to the end of the first 24 hours
measure: Zero Units PRBC and Died in Field or Emergency Department (ED)
timeFrame: From the time dispatch received 911 call to the time of death in the field or ED
measure: Zero Units PRBC and Died Within 6 Hours of Admission to the Hospital
timeFrame: The first 6 hours from the time of admission to the hospital
measure: Zero Units PRBC and Died Within 28 Days From the Time of the 911 Call
timeFrame: From the time dispatch received the 911 call to 28 days
measure: 1-9 Units PRBC in First 24 Hours
timeFrame: From the time dispatch received the 911 call to the end of the first 24 hours
measure: 1-9 Units PRBC and Died in Field or ED
timeFrame: From the time dispatch received 911 call to the time of death in the field or ED
measure: 1-9 Units PRBC and Died Within 6 Hours of Admission to the Hospital
timeFrame: The first 6 hours from the time of admission to the hospital
measure: 1-9 Units PRBC and Died Within 28 Days From the Time of the 911 Call
timeFrame: From the time dispatch received the 911 call to 28 days
measure: Greater Than 10 Units PRBC in First 24 Hours
timeFrame: From the time dispatch received the 911 call to the end of the first 24 hours
measure: Greater Than 10 Units PRBC and Died in Field or ED
timeFrame: From the time dispatch received 911 call to the time of death in the field or ED
measure: Greater Than 10 Units PRBC and Died Within 6 Hours of Admission to the Hospital
timeFrame: The first 6 hours from the time of admission to the hospital
measure: Greater Than 10 Units PRBC and Died Within 28 Days From the Time of the 911 Call
timeFrame: From the time dispatch received the 911 call to 28 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Resuscitaion Center, University of Alabama
state: Alabama
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: 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, 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.
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.