Clinical trial NCT00878631: Feasibility Trial of Traumatic Brain Injured Patients Randomized in the Prehospital Setting to Either Hypertonic Saline and Dextran Versus Normal Saline
Official title: The Toronto Prehospital Hypertonic Resuscitation Head Injury and Multi Organ Dysfunction Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Brain Injuries
Keywords: emergency medical services
traumatic brain injury
hypertonic saline with dextran
fluid resuscitation
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Sunnybrook Health Sciences Center, Toronto
name: Defence Research and Development Canada
First posted: 2009-04-09
Enrollment: 113
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: baseline survival rates for the treatment and control group to aid in the design of a definitive multicentre trial
timeFrame: survival at 48 hours, hospital discharge, 30 days and 4 months
measure: randomization compliance rate
timeFrame: duration of enrolment
measure: ease of protocol implementation in the out-of-hospital setting
timeFrame: duration of study
measure: adverse event rate of hypertonic saline dextran infusion
timeFrame: duration of study
Secondary outcomes:
measure: 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
timeFrame: discharge and at 4 months post incident
measure: 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.
timeFrame: at 4 and 12 months post incident
measure: magnetic resonance imaging to evaluate effects of HSD on brain atrophy post-injury
timeFrame: 4 months post incident
measure: 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
timeFrame: samples taken within 48 hours of incident
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
Study officials:
References:
citation: 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.
citation: 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.
citation: Rhind SG, Crnko NT, Baker AJ, Morrison LJ, Shek PN, Scarpelini S, Rizoli SB. Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients. J Neuroinflammation. 2010 Jan 18;7:5. doi: 10.1186/1742-2094-7-5.
citation: 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 data collection tools. Trials. 2009 Nov 20;10:105. doi: 10.1186/1745-6215-10-105.