The Toronto prehospital hypertonic resuscitation-head injury and multi organ dysfunction trial (TOPHR HIT)--methods and data collection tools.
BACKGROUND
Clinical trials evaluating the use of hypertonic saline in the treatment of hypovolemia and head trauma suggest no survival superiority over normal saline; however subgroup analyses suggest there may be a reduction in the inflammatory response and multiorgan failure which may lead to better survival and enhanced neurocognitive function. We describe a feasibility study of randomizing head injured patients to hypertonic saline and dextran vs. normal saline administration in the out of hospital setting.


METHODS
This feasibility study employs a randomized, placebo-controlled design evaluating normal saline compared with a single dose of 250 ml of 7.5% hypertonic saline in 6% dextran 70 in the management of traumatic brain injuries. The primary feasibility endpoints of the trial were: 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, and 4) adverse event 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.


CONCLUSIONS
We anticipate three aspects of the trial will present challenges to trial success; ethical demands associated with a waiver of consent trial, challenging follow up and comprehensive accurate timely data collection of patient identifiers and clinical or laboratory values. In addition all the data collection tools had to be derived de novo as none existed in the literature.


BACKGROUND
NCT00878631.
Morrison
Laurie J
LJ
Rescu, Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, 30 Bond St, Toronto Ontario, Canada. morrisonl@smh.toronto.on.ca
Rizoli
Sandro B
SB
Schwartz
Brian
B
Rhind
Shawn G
SG
Simitciu
Merita
M
Perreira
Tyrone
T
Macdonald
Russell
R
Trompeo
Anna
A
Stuss
Donald T
DT
Black
Sandra E
SE
Kiss
Alex
A
Baker
Andrew J
AJ
D003071:Cognition; D006259:Craniocerebral Trauma / Q000401:mortality / Q000523:psychology / Q000628:therapy*; D003625:Data Collection / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009102:Multiple Organ Failure / Q000401:mortality / Q000523:psychology / Q000628:therapy*; D012151:Resuscitation / Q000379:methods*; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*
D012462:Saline Solution, Hypertonic