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

This study has been completed.
Sponsor:
Collaborators:
Sunnybrook Health Sciences Center, Toronto
Defence Research and Development Canada
Information provided by:
St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier:
NCT00878631
First received: April 8, 2009
Last updated: NA
Last verified: April 2009
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Brain Injuries
Drug: hypertonic saline mixed with dextran
Drug: Normal Saline
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Toronto Prehospital Hypertonic Resuscitation Head Injury and Multi Organ Dysfunction Trial

Resource links provided by NLM:


Further study details as provided by St. Michael's Hospital, Toronto:

Primary Outcome Measures:
  • baseline survival rates for the treatment and control group to aid in the design of a definitive multicentre trial [ Time Frame: survival at 48 hours, hospital discharge, 30 days and 4 months ] [ Designated as safety issue: Yes ]
  • randomization compliance rate [ Time Frame: duration of enrolment ] [ Designated as safety issue: No ]
  • ease of protocol implementation in the out-of-hospital setting [ Time Frame: duration of study ] [ Designated as safety issue: Yes ]
  • adverse event rate of hypertonic saline dextran infusion [ Time Frame: duration of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: discharge and at 4 months post incident ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: at 4 and 12 months post incident ] [ Designated as safety issue: Yes ]
  • magnetic resonance imaging to evaluate effects of HSD on brain atrophy post-injury [ Time Frame: 4 months post incident ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: samples taken within 48 hours of incident ] [ Designated as safety issue: Yes ]

Enrollment: 113
Study Start Date: September 2004
Study Completion Date: December 2008
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Normal Saline
infusion of 250 ccs of Normal Saline within 4 hours of the accident
Drug: Normal Saline
250 ccs of normal saline infused within 4 hours of the accident
Experimental: 2 - hypertonic saline mixed with dextran
a single dose 250 ml of 7.5% hypertonic saline in 6% dextran 70 infused within 4 hours of the accident
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
Other Name: RescueFlow BioPhausia AB, Stockholm Sweden

Detailed 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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00878631

Locations
Canada, Ontario
Sunnybrook Health Sciences Center
Toronto, Ontario, Canada, M4N 3M5
St Michael's Hospital
Toronto, Ontario, Canada, M5V 1W8
Sponsors and Collaborators
St. Michael's Hospital, Toronto
Sunnybrook Health Sciences Center, Toronto
Defence Research and Development Canada
  More Information

Publications:
Morrison LJ, Rizoli S, Schwartz B, Rhind S, Black S, Stuss DT, Baker A, Univ of Toronto, Sunnybrook Health Sciences Centre, Toronto, Canada; on behalf of the TOPHR HIT Investigators. The Toronto Prehospital Resuscitation Head Injury and Multi-Organ Dysfunction Trial (TOPHR HIT). Circulation October 31, 2006; 114(18): #104.
Morrison LJ, Rizoli S, Schwartz B, Rhind S, Black S, Stuss DT, Baker A, Stuss DT, Baker A, Simitciu M, Perreira T, MacDonald RD. University of Toronto, Sunnybrook Health Sciences Center, Toronto, Canada; on behalf of the TOPHR HIT Investigators. The Toronto Prehospital Hypertonic Resuscitation Head Injury and Multi-Organ Dysfunction Trial (TOPHR HIT). Prehosp Emerg Care 2007; 11(1): 94.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Laurie Morrison, St Michael's Hospital
ClinicalTrials.gov Identifier: NCT00878631     History of Changes
Other Study ID Numbers: TOPHR HIT, No.w7711-027801/001/TOR
Study First Received: April 8, 2009
Last Updated: April 8, 2009
Health Authority: Canada: Health Canada

Keywords provided by St. Michael's Hospital, Toronto:
emergency medical services
traumatic brain injury
hypertonic saline with dextran
fluid resuscitation

Additional relevant MeSH terms:
Brain Injuries
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Dextrans
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Plasma Substitutes
Blood Substitutes

ClinicalTrials.gov processed this record on April 23, 2014