Clinical trial NCT03200613: Apixaban For Thromboprophylaxis In Patients With Acute Spinal Cord Injury
Official title: Apixaban Versus Low-Molecular Weight Heparin For Thromboprophylaxis In Patients With Acute Spinal Cord Injury: A Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Spinal Cord Injuries
Venous Thromboembolism
Keywords: Spinal cord injury
Venous thromboembolism
Hemorrhage
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2017-06-27
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Thromboprophylaxis options are limited for patients with acute spinal cord injury (SCI) and there are no studies on direct oral anticoagulants (DOACs) for thromboprophylaxis in this population. Participants will be randomized to apixaban 2.5 mg twice daily or standard dose low-molecular-weight heparin (LMWH), either enoxaparin 40 mg or dalteparin 5000 units, subcutaneously once daily for 90 days or until fully mobilized, whatever comes first. Thromboprophylaxis will be started as soon as hemostasis is achieved. The primary outcome for this pilot study will be the recruitment rate per year (i.e. the screened to enrolled ratio). The primary efficacy endpoint will be a composite of symptomatic, objectively verified, venous thromboembolism (VTE), defined as upper or lower limb deep vein thrombosis (DVT) and/or pulmonary embolism (PE) or sudden death where PE cannot be excluded. The primary safety endpoint will be major bleeding.

Detailed description: Patients with acute (SCI) have a high risk of VTE despite thromboprophylaxis. The current standard thrombprophylaxis is to use LMWH fas soon as hemostasis is achieved. The duration of thromboprophylaxis is commonly 3 months. This entails once or twice daily subcutaneous injections of LMWH for the patients for this duration, which is inconvenient for the patients. There are currently no studies on use of DOACs for thromboprophylaxis in patients with SCI.

We will perform a pilot study at Hamilton General on apixaban versus LMWH for thromboprophylaxis in patients with acute SCI. Upon providing written informed consent, eligible patients will be randomized to apixaban 2.5 mg twice daily or LMWH, either enoxaparin 40 mg or dalteparin 5000 units, subcutaneously once daily for 90 days or until fully mobilized, whatever comes first.

The primary outcome for the feasibility study will be the recruitment rate per year (i.e. the screened to enrolled ratio). Other key feasibility measures will be accrual ratio, protocol violations pertaining to eligibility criteria and randomization procedures, retention rate for primary end-point assessment at 1 year, and the estimates of endpoint rates in the population. The primary efficacy endpoint will be a composite of symptomatic, objectively verified VTE (upper or lower limb DVT and/or PE) or sudden death where PE cannot be excluded. The primary safety endpoint will be major bleeding.

This will be the first study comparing the use of LMWH against a DOAC in SCI patients. Use of a DOAC such as apixaban can eliminate the burden associated with daily injections for the patients.

Eligibility criteria: Inclusion Criteria:

* Adult patients (≥18 years old) with acute spinal cord injury (SCI) presenting to the hospital within 1 week of SCI and is at least 36 h after the injury
* Traumatic SCI
* SCI with or without other injuries

Exclusion Criteria:

* Already on therapeutic oral anticoagulation prior to enrollment
* Active bleeding, intracranial or perispinal hematoma, or acquired or congenital bleeding disorder
* Pregnancy or breast feeding
* Severe renal failure (creatinine clearance ≤30 ml/min)
* Liver cirrhosis
* Severe thrombocytopenia (platelets \<50)
* Attending physician believes that the patient is not suitable for the study (for example, psychiatric disorder; history of non-compliance)
* Geographic inaccessibility: planned transfer to other site where follow-up not possible
* Failure to obtain written consent
* Previous hypersensitivity reaction to study drugs
* Patients with expected short hospital admission (≤7 days) due to minor injury

Primary outcomes:
measure: Primary feasibility outcome: recruitment rate per year (i.e. the screened to enrolled ratio)
timeFrame: 24 months
Secondary outcomes:
measure: Composite of Symptomatic Venous Thromboembolism or Sudden Death Where Pulmonary Embolism Cannot be Excluded
timeFrame: 24 months
measure: Major Bleeding
timeFrame: 24 months
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
Study officials:
References:
citation: Piran S, Schulman S. Incidence and risk factors for venous thromboembolism in patients with acute spinal cord injury: A retrospective study. Thromb Res. 2016 Nov;147:97-101. doi: 10.1016/j.thromres.2016.09.030. Epub 2016 Oct 3.
citation: Piran S, Schulman S. Thromboprophylaxis in Patients with Acute Spinal Cord Injury: A Narrative Review. Semin Thromb Hemost. 2019 Mar;45(2):150-156. doi: 10.1055/s-0039-1678720. Epub 2019 Feb 11.