The Toronto Prehospital Hypertonic Resuscitation Head Injury and Multi Organ Dysfunction Trial (TOPHR HIT)

Study Overview
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Brief Summary
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The TOPHR HIT trial is a clinical trial of patients experiencing blunt trauma who present with an injury to their head which makes them unconscios. The study compares two different fluids given to the patient in the out of hospital setting by a paramedic. The two fluids are salt water (standard treatment) versus a higher concentration of salt water mixed with a sugar (study fluid). The patients have an equal chance of receiving either fluid and the paramedic and the patient and the treating trauma surgeon do not know which fluid was provided in the out of hospital setting.

Detailed Description
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Study Objective 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 Hypertonic Saline Dextran (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.

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

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Biological: hypertonic saline mixed Dextran
* Biological: Saline solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥16 Initial assessment of Glasgow Coma Score (GCS) 8 or less Blunt traumatic mechanism of injury Exclusion Criteria: Known pregnancy Penetrating primary injury VSA prior to randomization; previous intravenous therapy ≥ 50 ml Time interval between arrival at scene and intravenous access exceeds four hours Amputation of above wrist or ankle Any burn (thermal, chemical, electrical, radiation) Suspected hypothermia Asphyxia (strangulation, hanging, choking, suffocation, drowning) and 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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hypertonic saline mixed Dextran<br>hypertonic saline mixed Dextran | Biological: hypertonic saline mixed Dextran<br>* single dose administered intravenously<br>|
| Placebo Comparator: Placebo controlled<br>Saline solution | Biological: Saline solution<br>* placebo - saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30 day survival |  | 30 days after discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | •Survival: 48 hours after admission; Hospital discharge | 48 hrs after admission | 
| Functional neurological outcomes at 4 months |  | 4 Months | 
| Neuropsychological testing at 4 months |  | 4 months | 
| Neuropsychological testing at 1 year |  | 1 year | 
| Physiologic parameters indicative of organ dysfunction |  | 4 months | 
| Structural parameters indicative of brain injury or dysfunction at 4 months |  | 4 months | 
| Serum inflammatory markers measured on arrival, 12, 24, 48 hours later |  | 12, 24, 48 hours later | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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resuscitation