Traumatic Brain Injury
Conditions
Keywords
Sequential Compression Device, Anticoagulant Thromboprophylaxis, Deep Vein Thrombosis, Sub Cutaneous, VTE
Brief summary
This is a phase III, multi-centre, double blind, randomized controlled trial of patients with traumatic brain injury (TBI).
Detailed 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.
Interventions
DRUGDalteparin
Dalteparin in prophylactic doses administered daily if screening criteria are satisfied.
DRUGSaline
Saline in prophylactic doses administered daily if screening criteria are satisfied.
Sponsors
Sunnybrook Research Institute
Sunnybrook Health Sciences Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinically important VTE | 8 days | Composite outcome of clinically-important VTE within 7±1 days after randomization defined as any of: 1. Symptomatic, objectively-confirmed pulmonary embolism (PE), or 2. Symptomatic, objectively-confirmed, proximal leg deep vein thrombosis (DVT), or 3. Proximal (above knee) leg DVT on compression ultrasonography on Day 7±1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objectively confirmed new or progressing ICB on radiology, | 8 days | Assessed by comparing the initial brain CT (Day 0) to that performed within 8±1 days following randomization (or most recent prior to death). |
| 180-day Mortality | 180 days | Mortality at 180 days |
| 7-day Mortality | 7 days | Mortality at 7 days |
| 30-day Mortality | 30 days | Mortality at 30 days |
| Clinically-important ICB (Intracranial bleeding) progression | 7 days | Clinically-important ICB progression within 7±1 days after randomization , as defined by having (1) any increase in volume of blood in the brain on any CT scan within 7±1 days relative to initial CT scan on Day 0\* AND (2) clinical worsening within 24 hours of this CT scan, defined by one or more of the following: * Surgical intervention related to increased ICB after Day 0 (craniotomy/craniectomy, ICP monitor, external ventricular drain) * Decrease of GCS (Glasgow Coma Scale) by at least 2 points not related to sedation * Increase in ICP \>5 mmHg on 2 occasions at least 6 hours apart despite medical therapy (if ICP monitor is in place) * Death |
| Functional neurological outcome at day 30 as measured by Glasgow Outcome Scale Extended | 30 days | Glasgow Outcome Scale Extended (GOSE) at Day 30±5 by phone interview. |
| Functional neurological outcome at day 180 as measured by Glasgow Outcome Scale Extended | 180 days | Glasgow Outcome Scale Extended (GOSE) at Day 180±14 by phone interview. |
| Quality of life outcome at 30 days as measured by the EuroQol5D | 30 days | EQ-5D (EuroQol 5D) at Day 30±5 by phone interview. |
| Quality of life outcome at 180 days as measured by the EuroQol5D | 180 days | EQ-5D (EuroQol 5D) at Day 180±14 by phone interview. |
| Delayed VTE after day 7 | 30 days | Any clinically important VTE occurring between Day 8 to Day 30 detected by treating clinicians |
Countries
Canada
Contacts
Primary ContactFarhad Pirouzmand, MD, MSc, FRCSC
Backup ContactKanthi Kavikondala, CCRP
Outcome results
None listed