OPtimal Timing of Thromboprophylaxis in Traumatic IntraCranial Haemorrhage (OPTTTICH Study)
Victims of trauma with severe head injury who have bled into their brains are at high risk of developing blood clots in their legs. These blood clots can break off and travel through the bloodstream to the lungs causing death. Blood thinners can be given to patients to prevent blood clots from developing but this can leave patients at risk for additional bleeding in the brain causing further damage or death. The earlier blood thinners are started the more effective they are at preventing blood clots but some patients with severe head injury who have bled into their brains will develop further bleeding even if they do not receive blood thinners. Even though a growing body of research has shown that the majority of bleeding in the brain stops within the first 24 hours after injury and that it is safe to start blood thinners as early as 24 hours after injury, doctors are still waiting longer than 4 days to start blood thinners in these patients over concerns of worsening bleeding. In Canada, almost half of the patients with severe head injury do not receive blood thinners until at least five days after injury. Delays in starting blood thinners appear to put patients at increased risk of developing blood clots, unnecessarily. This study will compare the benefits of starting low-molecular weight heparin (LMWH), a type of blood thinner, early (less than 48 hours) versus the current practice (waiting until the 5th day after being injured) in preventing blood clots in patients who have bled into their brains after severe head injury. The investigators believe that starting LMWH earlier will be more effective in preventing blood clots without worsening any bleeding when compared to waiting to start blood thinners. This study is called OPTTTICH (Optimal Timing of Thromboprophylaxis in Traumatic IntraCranial Haemorrhage) and will be the largest Canadian investigator-initiated randomized control trial on blood clot prevention in trauma patients with severe head injury who have bled into their brains.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||OPtimal Timing of Thromboprophylaxis in Traumatic IntraCranial Haemorrhage (OPTTTICH Study)|
- Proximal lower limb deep vein thrombosis (DVT) diagnosed by bilateral lower extremity compression ultrasound. [ Time Frame: Maximum of 60 days or until hospital discharge. ] [ Designated as safety issue: Yes ]Ultrasounds will be performed within 72 hours of enrollment as well as twice weekly when in ICU and weekly thereafter. Non-compressibility of 1 or more proximal deep venous segments on compression US will be considered diagnostic. Each segment will be assessed as fully compressible, partially compressible, not compressible, or not well visualized. All positive ultrasounds will be recorded and stratified into above knee (proximal DVT) or below knee (distal DVT). Patients who have both proximal and distal vein thrombus will be classified as having proximal DVT.
- Non-intracranial bleeding [ Time Frame: Maximum of 60 days or until hospital discharge. ] [ Designated as safety issue: Yes ]Non-intracranial bleeding events will be recorded and classified as either major or minor bleeding, according to a modified bleeding assessment tool adapted to our patient population.
- Pulmonary Embolism [ Time Frame: Maximum of 60 days or until hospital discharge ] [ Designated as safety issue: Yes ]Patients who develop clinical suspsicion of PE will have a helical CT chest. Pulmonary embolism will be diagnosed by the presence of an intraluminal filling defect detected in either the main,lobar,or segmental branches of the pulmonary artery. Patients with a high probability of PE on clinical grounds but with negative CT chest will undergo a ventilation-perfusion scan.
- Intracranial haemorrhage progression (IHP). [ Time Frame: Maximum of 60 days or until hospital discharge. ] [ Designated as safety issue: Yes ]If a Patient develops clinical evidence of neurological deterioration an emergent head CT scan will be performed.The CT scan will be reviewed by the blinded attending neuroradiologist. A comparison to the previous CT scan will be made and assessed for evidence of IHP. Intracranial haemorrhage progression will be defined as either 1) the development of a new haematoma, 2) any enlargement of an existing haematoma by an attending neuroradiologist's CT report, or 3) any progression of haematoma by the Marshall Head CT Classification System.
|Study Start Date:||September 2010|
|Estimated Study Completion Date:||September 2012|
|Estimated Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Early initiation of thromboprophylaxis
Early initiation of thromboprophylaxis with Enoxaparin between 36-48 hours post injury to day 5, followed by standard of care (DVT prophylaxis with Enoxaparin) starting day 6 post injury.
Enoxaparin 30 mg subcutaneously twice daily for six doses starting 36-48 hours post traumatic injury.
Other Name: Lovenox
Placebo Comparator: Late initiation of thromboprophylaxis
Initiation of placebo 36-48 hours post traumatic injury until day 5, then standard of care (DVT prophylaxis with Enoxaparin) starting on Day 6.
0.9% normal saline in equal volume to active comparator given subcutaneously twice daily starting 36-48 hours post traumatic injury for six doses.
|Hamilton Health Sciences- General site|
|Hamilton, Ontario, Canada, L8L 2X2|
|Principal Investigator:||Niv Sne, MD FRCSC||Hamiltn Health Sciences/McMaster University|