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

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

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.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Biological: hypertonic saline mixed Dextran; Biological: Saline solution

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 Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Defence Research and Development Canada

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: July 11, 2012
• First Submitted That Met QC Criteria: July 13, 2012
• First Posted (Estimate): July 17, 2012

Study Record Updates

• Last Update Posted (Estimate): July 17, 2012
• Last Update Submitted That Met QC Criteria: July 13, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: resuscitation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Craniocerebral Trauma; Anticoagulants; Plasma Substitutes; Blood Substitutes; Dextrans
• Other Study ID Numbers: TOPHR HIT