OPtimal Timing of Thromboprophylaxis in Traumatic IntraCranial Haemorrhage (OPTTTICH Feasibility Study)

NCT01589393 | Completed

• 1 other identifier: CIHR-2009
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Traumatic Intracranial Haemorrhage

Keywords

Trauma; Thromboprophylaxis; Intracranial haemorrhage; Deep vein Thrombosis

Outcome Measures

Primary Outcomes (1)

• Proximal lower limb deep vein thrombosis (DVT) diagnosed by bilateral lower extremity compression ultrasound.

  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.

  Maximum of 60 days or until hospital discharge.

Secondary Outcomes (3)

• Non-intracranial bleeding

  Maximum of 60 days or until hospital discharge.

• Pulmonary Embolism

  Maximum of 60 days or until hospital discharge

• Intracranial haemorrhage progression (IHP).

  Maximum of 60 days or until hospital discharge.

Study Arms (2)

Early initiation of thromboprophylaxis

ACTIVE COMPARATOR

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.

Drug: Enoxaparin

Late initiation of thromboprophylaxis

PLACEBO COMPARATOR

Initiation of placebo 36-48 hours post traumatic injury until day 5, then standard of care (DVT prophylaxis with Enoxaparin) starting on Day 6.

Other: Placebo

Interventions

Enoxaparin DRUG

Enoxaparin 30 mg subcutaneously twice daily for six doses starting 36-48 hours post traumatic injury.

Also known as: Lovenox

Early initiation of thromboprophylaxis

Placebo OTHER

0.9% normal saline in equal volume to active comparator given subcutaneously twice daily starting 36-48 hours post traumatic injury for six doses.

Late initiation of thromboprophylaxis

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Multi-system trauma patients referred to the trauma service with a non-progressing tICH documented on 24-hour repeat head CT scan

You may not qualify if:

• Less than 16 years of age
• Unexpected to survive or to remain in hospital \>72 hours
• Known malignancy under active care at time of admission
• Known DVT, PE, or other condition requiring anticoagulation at time of admission
• Coagulopathy (defined as international normalized ratio (INR) values \>1.5 times the upper limit of normal, or partial thromboplastin time (PTT) values \>1.5 times the upper limit of normal) at 24 hours after admission
• Platelet count \<75 x 109/L at 24 hours after admission
• Bilateral lower limb amputation
• History of allergy to heparin or suspected or proven HIT
• Limitation of life support or palliative care
• Prior enrolment in this trial or currently in a confounding randomized trial
• Pregnancy
• Study drug (LMWH or placebo) not administered within 36-48 hours post-injury
• Grade V liver or splenic injuries that have not received definitive care (e.g. embolization, surgical intervention) within 36-48 hours after injury
• Persistent intracranial pressure \>20 mm Hg
• Spinal subdural haematoma or spinal epidural haematoma

Sponsors & Collaborators

• McMaster University: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Hamilton Health Sciences- General site

Hamilton, Ontario, L8L 2X2, Canada

Location

MeSH Terms

Conditions

Intracranial Hemorrhage, Traumatic; Wounds and Injuries; Intracranial Hemorrhages; Venous Thrombosis

Interventions

Enoxaparin

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thrombosis; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Niv Sne, MD FRCSC

  Hamiltn Health Sciences/McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2012
• First Posted: May 2, 2012
• Study Start: September 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: March 22, 2018

Record last verified: 2012-04

Locations

CA (1)