OPtimal Timing of Thromboprophylaxis in Traumatic IntraCranial Haemorrhage - Pilot Study

NCT02260908 | Unknown

• 1 other identifier: OPT1-22-06-10
• Study Type: interventional
• Target: 300
• 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, resulting in 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. In addition, 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 (36 to 48 hours after injury) versus the current practice (waiting until the 6th 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 OPTTICH (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 (US).

  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 US will be recorded and stratified into above-knee (proximal DVT) or below-knee (distal DVT). Patients who have both proximal and distal DVT 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 (PE)

  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 until day 5, followed by standard of care (DVT prophylaxis with Enoxaparin) starting on post-injury day 6.

Drug: Enoxaparin

Late initiation of thromboprophylaxis

PLACEBO COMPARATOR

Initiation of placebo (normal saline) 36-48 hours post-injury until day 5, followed by standard of care (DVT prophylaxis with Enoxaparin) starting on post-injury 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 for six doses, starting 36-48 hours post-traumatic injury.

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:

• Unexpected to survive or 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 10\^9/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 enrollment 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
• Intracranial haemorrhage progression on 24-hour repeat CT scan

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

RECRUITING

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

  Hamilton Health Sciences/McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Niv Sne, MD FRCSC

CONTACT

905-527-4322; nivsne@yahoo.ca

Timothy Rice, MD

CONTACT

905-527-4322; timothy.rice@medportal.ca

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: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Niv Sne, Director of Trauma Research

Study Record Dates

• First Submitted: October 6, 2014
• First Posted: October 9, 2014
• Study Start: October 1, 2014
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: April 10, 2015

Record last verified: 2015-04

Locations

CA (1)