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

Brain Injuries Clinical Trial

— TOPHR HIT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00878631
• Other study ID #: TOPHR HIT
• Secondary ID: No.w7711-027801/
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: April 8, 2009
• Last updated: April 8, 2009
• Start date: September 2004
• Est. completion date: December 2008

Study information

• Verified date: April 2009
• Source: St. Michael's Hospital, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 113
• Est. completion date: December 2008
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Injuries

Intervention

Drug:
• hypertonic saline mixed with dextran
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
• Normal Saline
250 ccs of normal saline infused within 4 hours of the accident

Locations

Country	Name	City	State
Canada	St Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Center	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
St. Michael's Hospital, Toronto	Defence Research and Development Canada, Sunnybrook Health Sciences Center, Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Morrison LJ, Rizoli SB, Schwartz B, Rhind SG, Simitciu M, Perreira T, Macdonald R, Trompeo A, Stuss DT, Black SE, Kiss A, Baker AJ. The Toronto prehospital hypertonic resuscitation-head injury and multi organ dysfunction trial (TOPHR HIT)--methods and dat — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	randomization compliance rate		duration of enrolment	No
Primary	ease of protocol implementation in the out-of-hospital setting		duration of study	Yes
Primary	adverse event rate of hypertonic saline dextran infusion		duration of study	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	magnetic resonance imaging to evaluate effects of HSD on brain atrophy post-injury		4 months post incident	Yes
Secondary	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	Yes