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

Unity Health Toronto

Status and phase: Completed; Phase 3; Phase 2

Conditions: Brain Injuries

Treatments: Drug: Normal Saline; Drug: hypertonic saline mixed with dextran

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00878631

No.w7711-027801/001/TOR

TOPHR HIT

Details and patient eligibility

About

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.

Full description

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:

1. baseline survival rates for the treatment and control group to aid in the design of a definitive multicentre trial.
2. randomization compliance rate.
3. ease of protocol implementation in the out-of-hospital setting.
4. 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.

Enrollment: 113 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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113 participants in 2 patient groups

1 Normal Saline

Active Comparator group

Description:

infusion of 250 ccs of Normal Saline within 4 hours of the accident

Treatment:

Drug: Normal Saline

2 - hypertonic saline mixed with dextran

Experimental group

Description:

a single dose 250 ml of 7.5% hypertonic saline in 6% dextran 70 infused within 4 hours of the accident

Treatment:

Drug: hypertonic saline mixed with dextran