Hypertonic Resuscitation Following Traumatic Injury

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 3 Study of Hypertonic Resuscitation Following Traumatic Injury With Hypovolemic Shock

Conditions
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Shock, Traumatic

Intervention / Treatment
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* Drug: 7.5% hypertonic saline/6% Dextran-70 (HSD)
* Drug: 7.5% hypertonic saline (HS)
* Drug: 0.9% normal saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>7.5% hypertonic saline/6% Dextran-70 (HSD) | Drug: 7.5% hypertonic saline/6% Dextran-70 (HSD)<br>* 250 cc dose given as a one-time intravenous (IV) bolus in the pre-hospital setting.<br>* Other names: RescueFlo;|
| Experimental: 2<br>7.5% hypertonic saline (HS) | Drug: 7.5% hypertonic saline (HS)<br>* 250 cc dose given as a one-time IV bolus in the pre-hospital setting.<br>|
| Placebo Comparator: 3<br>0.9% normal saline | Drug: 0.9% normal saline<br>* 250 cc dose given as a one-time IV bolus in the pre-hospital setting.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 Day Survival | 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 days from time of Emergency Department (ED) arrival | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adult Respiratory Distress Syndrome(ARDS)-Free Survival Through Day 28 | Absence of diagnosis of Adult Respiratory Distress Syndrome and alive through day 28 | 28 days from time of ED arrival | 
| Worst Multiple Organ Dysfunction Score (MODS) Mean Through Day 28 | 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. | 28 days from time of ED arrival | 
| Presence of Nosocomial Infection Through Day 28 | Includes one or more nosocomial infections from the following list: pneumonia, blood stream infection, urinary tract infection and wound infection | Within 28 days of injury, while hospitalized | 
| Packed Red Blood Cells (PRBC) First 24 Hours | The numbers of units of packed red blood cells transfused in the first 24 hours | First 24 hours from the time of 911 call | 
| Total Fluids First 24 Hours | 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 | First 24 hours from the time of of 911 call | 
| Ventilator-free Days Through Day 28 | 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 | Duration of hospital stay through day 28 | 
| Days Alive Out of the Intensive Care Unit (ICU) Through Day 28 | The number of days the patient is alive and not being cared for in the intensive care unit | First 28 days from the time of 911 call | 
| Days Alive Out of the Hospital Through Day 28 | The number of days the patient is alive and no longer an inpatient in the hospital through day 28 | First 28 days from the time of 911 call | 
| Survival at Hospital Discharge | Alive at the time of discharge from the Level One or Two trauma hospital. This did not include disposition from rehabilitation facilities. | Duration of hospital stay through to discharge | 
| Zero Units PRBC in First 24 Hours | This is the total number of subjects who received no blood products in the first 24 hours from the time of the 911 call. | From the time dispatch received the 911 call to the end of the first 24 hours | 
| Zero Units PRBC and Died in Field or Emergency Department (ED) | 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. | From the time dispatch received 911 call to the time of death in the field or ED | 
| Zero Units PRBC and Died Within 6 Hours of Admission to the Hospital | 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. | The first 6 hours from the time of admission to the hospital | 
| Zero Units PRBC and Died Within 28 Days From the Time of the 911 Call | 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. | From the time dispatch received the 911 call to 28 days | 
| 1-9 Units PRBC in First 24 Hours | 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. | From the time dispatch received the 911 call to the end of the first 24 hours | 
| 1-9 Units PRBC and Died in Field or ED | 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. | From the time dispatch received 911 call to the time of death in the field or ED | 
| 1-9 Units PRBC and Died Within 6 Hours of Admission to the Hospital | 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). | The first 6 hours from the time of admission to the hospital | 
| 1-9 Units PRBC and Died Within 28 Days From the Time of the 911 Call | 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). | From the time dispatch received the 911 call to 28 days | 
| Greater Than 10 Units PRBC in First 24 Hours | 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. | From the time dispatch received the 911 call to the end of the first 24 hours | 
| Greater Than 10 Units PRBC and Died in Field or ED | 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). | From the time dispatch received 911 call to the time of death in the field or ED | 
| Greater Than 10 Units PRBC and Died Within 6 Hours of Admission to the Hospital | 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). | The first 6 hours from the time of admission to the hospital | 
| Greater Than 10 Units PRBC and Died Within 28 Days From the Time of the 911 Call | 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). | From the time dispatch received the 911 call to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trauma, Shock