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

Phase 3

Completed

• Conditions: Traumatic Brain Injury
• Interventions: Biological: hypertonic saline mixed Dextran; Biological: Saline solution

• Registration Number: NCT01642524
• Lead Sponsor: Sunnybrook Health Sciences Centre

Brief Summary

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

Study Objective

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 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.

Study Timeline

• Study Start: 2004-04
• Primary Completion: 2006-01
• Study Completion: 2011-07
• Status Verified: 2012-07
• Study First Submitted: 2012-07-11
• Study First Submitted QC: 2012-07-13
• Last Update Submitted: 2012-07-13
• Study First Posted: 2012-07-17
• Last Update Posted: 2012-07-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 114

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
hypertonic saline mixed Dextran	hypertonic saline mixed Dextran	hypertonic saline mixed Dextran
Placebo controlled	Saline solution	Saline solution

Primary Outcome Measures

Name	Time	Method
30 day survival	30 days after discharge

Secondary Outcome Measures

Name	Time	Method
Survival	48 hrs after admission	•Survival: 48 hours after admission; Hospital discharge
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