Feasibility Trial of Traumatic Brain Injured Patients Randomized in the Prehospital Setting to Either Hypertonic Saline and Dextran Versus Normal Saline

Study Overview
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Brief Summary
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This clinical trial will evaluate the ease of conducting a randomized trial on patients with severe head injury who are cared for by paramedics in the out of hospital setting. The trial will compare two different kinds of fluids that are commonly used to elevate blood pressure and minimize the impact of the brain injury. The two solutions are a salt solution of different concentrations. One is a normal saline solution similar to the consistency of human blood and the other is a higher concentration mixed with a sugar that helps to keep the solution in the blood stream longer. This study is conducted without patient consent at the time of the study enrolment. The study will report on whether this trial is feasible in the out of hospital setting before launching into a larger definitive trial.

Detailed Description
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The Toronto Prehospital Hypertonic Resuscitation-Head Injury and Multi Organ Dysfunction Trial (TOPHR HIT) is a randomized, placebo-controlled out of hospital trial of blunt trauma patients with head injuries. The study compares a group receiving normal saline according to a paramedic's protocol, with a treatment group receiving a single dose 250 ml of 7.5% hypertonic saline in 6% dextran 70 (RescueFlow BioPhausia AB, Stockholm Sweden). The primary objective of this study is to report feasibility in accordance with the methodology described by Lancaster and Dodds*, specifically addressing: baseline survival rates for the treatment and control group to aid in the design of a definitive multicentre trial. randomization compliance rate. ease of protocol implementation in the out-of-hospital setting. adverse rate of HSD infusion. The secondary objectives include measuring the effect of HSD in modulating the immuno-inflammatory response to severe head injury and its effect on modulating the release of neuro-biomarkers into serum; evaluating the role of serum neuro-biomarkers in predicting patient outcome and clinical response to HSD intervention; evaluating effects of HSD on brain atrophy post-injury and neurocognitive and neuropsychological outcomes. *Lancaster, G.A., S. Dodd, and P.R. Williamson, Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract, 2004. 10(2): p. 307-12.

Official Title
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The Toronto Prehospital Hypertonic Resuscitation Head Injury and Multi Organ Dysfunction Trial

Conditions
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Brain Injuries

Intervention / Treatment
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* Drug: hypertonic saline mixed with dextran
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 16; Initial assessment of GCS 8 or less; Blunt traumatic mechanism of injury. Exclusion Criteria: Known pregnancy; Primary injury penetrating; VSA prior to randomization; Previous Intravenous therapy ≥ 50 ml; Time interval between arrival at scene and intravenous access exceeds four hours; Amputation above wrist or ankle; Any burn (thermal, chemical, electrical, radiation) Suspected hypothermia; Asphyxia (strangulation, hanging, choking, suffocation, drowning) Fall from height ≤ 1m or ≤ 5 Stairs

Ages Eligible for Study
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Minimum Age: 16 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 |
| --- | --- |
| Active Comparator: 1 Normal Saline<br>infusion of 250 ccs of Normal Saline within 4 hours of the accident | Drug: Normal Saline<br>* 250 ccs of normal saline infused within 4 hours of the accident<br>|
| Experimental: 2 - hypertonic saline mixed with dextran<br>a single dose 250 ml of 7.5% hypertonic saline in 6% dextran 70 infused within 4 hours of the accident | Drug: hypertonic saline mixed with dextran<br>* a single dose 250 ml of 7.5% hypertonic saline in 6% dextran 70 is given within 4 hours from the time of the accident<br>* Other names: RescueFlow BioPhausia AB, Stockholm Sweden;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| baseline survival rates for the treatment and control group to aid in the design of a definitive multicentre trial |  | survival at 48 hours, hospital discharge, 30 days and 4 months | 
| randomization compliance rate |  | duration of enrolment | 
| ease of protocol implementation in the out-of-hospital setting |  | duration of study | 
| adverse event rate of hypertonic saline dextran infusion |  | duration of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| neurocognitive outcomes at discharge (cerebral performance category) and at 4 months (functional independence measure, disability rating scale, Glasgow Outcome Scale and Glasgow outcome Scale Extended |  | discharge and at 4 months post incident | 
| neuropsychological outcomes including learning and memory, working memory, executive function, language function, visuospatial function, speed of processing and Beck Depression Scale. A focused attention reaction time test was added to 12 month testing. |  | at 4 and 12 months post incident | 
| magnetic resonance imaging to evaluate effects of HSD on brain atrophy post-injury |  | 4 months post incident | 
| the effect of HSD in modulating the immuno-inflammatory response to severe head injury and its effect on modulation the release of neuro-biomarkers into serum; evaluating the role of serum neuro-biomarkers in predicting patient outcome |  | samples taken within 48 hours of incident | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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emergency medical services, traumatic brain injury, hypertonic saline with dextran, fluid resuscitation