OPtimal Timing of Thromboprophylaxis in Traumatic IntraCranial Haemorrhage - Pilot Study

Traumatic Intracranial Haemorrhage Clinical Trial

— OPTTICH  

Official title:

OPTTICH Pilot Study - OPtimal Timing of Thromboprophylaxis in Traumatic IntraCranial Haemorrhage

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02260908
• Other study ID #: OPT1-22-06-10
• Status: Recruiting
• Phase: N/A
• First received: October 6, 2014
• Last updated: April 8, 2015
• Start date: October 2014
• Est. completion date: September 2016

Study information

• Verified date: April 2015
• Source: McMaster University
• Contact: Niv Sne, MD FRCSC
• Phone: 905-527-4322
• Email: nivsne[@]yahoo.ca
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hemorrhage
• Intracranial Hemorrhage, Traumatic
• Intracranial Hemorrhages
• Traumatic Intracranial Haemorrhage

Intervention

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

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

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences- General site	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
McMaster University	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Secondary	Non-intracranial bleeding	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.	Maximum of 60 days or until hospital discharge.	Yes
Secondary	Pulmonary Embolism (PE)	Patients who develop clinical suspicion 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 or the pulmonary artery. Patients with a high probability of PE on clinical grounds but with negative CT chest will undergo a ventilation-perfusion scan.	Maximum of 60 days or until hospital discharge.	Yes
Secondary	Intracranial haemorrhage progression (IHP)	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.	Maximum of 60 days or until hospital discharge.	Yes