Apixaban For Thromboprophylaxis In Patients With Acute Spinal Cord Injury

Sponsor

McMaster University (Other)

Overall Status

Terminated

CT.gov ID

NCT03200613

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injuries Venous Thromboembolism	Drug: Apixaban Drug: Low molecular weight heparin	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

Open Label

Primary Purpose:

Prevention

Official Title:

Apixaban Versus Low-Molecular Weight Heparin For Thromboprophylaxis In Patients With Acute Spinal Cord Injury: A Pilot Study

Actual Study Start Date :

Sep 1, 2017

Actual Primary Completion Date :

Jul 1, 2019

Actual Study Completion Date :

Aug 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apixaban Apixaban 2.5 mg orally twice daily	Drug: Apixaban 2.5 mg orally twice daily Other Names: Eliquis
Active Comparator: Low Molecular Weight Heparin Either enoxaparin 40 mg or dalteparin 5000 units subcutaneously once daily	Drug: Low molecular weight heparin Dalteparin 5000 units daily or Enoxaparin 40 mg subcutaneous daily Other Names: Lovenox or Fragmin

Arm

Intervention/Treatment

Experimental: Apixaban

Apixaban 2.5 mg orally twice daily

Drug: Apixaban

2.5 mg orally twice daily

Other Names:

Eliquis

Active Comparator: Low Molecular Weight Heparin

Either enoxaparin 40 mg or dalteparin 5000 units subcutaneously once daily

Drug: Low molecular weight heparin

Dalteparin 5000 units daily or Enoxaparin 40 mg subcutaneous daily

Other Names:

Lovenox or Fragmin

Outcome Measures

Primary Outcome Measures

Primary feasibility outcome: recruitment rate per year (i.e. the screened to enrolled ratio) [24 months]
The investigators define success as the ability to identify 20 eligible patients at each center per 12-month period.

Secondary Outcome Measures

Composite of Symptomatic Venous Thromboembolism or Sudden Death Where Pulmonary Embolism Cannot be Excluded [24 months]
A composite of symptomatic, objectively verified VTE (upper or lower limb DVT and/or PE) or sudden death where PE cannot be excluded
Major Bleeding [24 months]
Major bleeding according to the International Society on Thrombosis and Haemostasis definition

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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