Overview
This is a pilot study, phase III, multi-centre, double blind, randomized controlled trial of patients with traumatic brain injury (TBI).
Description
Patients with severe brain injury are at risk for developing blood clots in their legs, which can travel to the lungs. This potentially serious complication is known as venous thromboembolism (VTE). Anticoagulants are commonly used to prevent VTE in hospital patients. However, in patients with major head injury, anticoagulant prevention is commonly delayed for the fear that it can potentially lead to further bleeding in the brain. Another method that aims to prevent blood clots involves the use of sequential compression device (SCD) that compress the legs and increase the flow of blood in the leg veins.
This study will compare results from patients who receive the SCDs only to those who receive both SCD and anticoagulants. The outcome of this study will provide information about how best to prevent blood clots while not increase brain bleeding after head injury.
Eligibility
Inclusion Criteria
The pragmatic nature of this study seeks to include all consecutive patients presenting
with significant TBI, regardless of whether ICB is evident at presentation. Inclusion
criteria are the following:
i) Patients with severe TBI defined as GCS of ≤8, or
ii) Patients with moderate TBI defined as GCS = 9-12, admitted to ICU, with at least some
ICB present on initial CT scan and any of the following:
1. Requiring invasive mechanical ventilation at the time of screening
2. Increased ICB on repeat CT scan compared to initial CT scan
iii) Upon randomization the patient will be able to receive the first dose of study drug in
the first 3 calendar days from the time of injury
iv) ≥ 18 years of age
Exclusion Criteria
All participants meeting any of the following exclusion criteria at baseline will be
excluded from participation in this study:
i) Known Hypersensitivity to FRAGMIN (Dalteparin), or its constituents including benzyl
alcohol or to other low molecular weight heparins and/or heparins or pork products
ii) Known history of confirmed or suspected immunologically-mediated heparin-induced
thrombocytopenia (delayed-onset severe thrombocytopenia), and/or in patients with a known
history of a positive in vitro platelet-aggregation test in the presence of FRAGMIN
(Dalteparin) is positive
iii) Known septic endocarditis
iv) Uncontrollable active bleeding
v) Known major blood clotting disorders
vi) Known acute gastroduodenal ulcer (with active bleeding)
vii) Severe uncontrolled hypertension (i.e. BP>210 despite medications)
viii) Known diabetic or hemorrhagic retinopathy
ix) Anticipated to be unable to receive SCD on at least one lower extremity due to nature
of injuries for duration of intervention period
x) Presence of another confounding factor that can adequately explain the poor GCS at time
of presentation (e.g. drug toxicity, seizure)
xi) Known presence of irreversible coagulopathies
xii) Known Pregnancy
xiii) Participants extremely low weight (<45 kg), or extremely high weight (>120kg)
xiv) Not expected to survive more than 48 hours from admission