Apixaban For Thromboprophylaxis In Patients With Acute Spinal Cord Injury

NCT ID: NCT03200613

Last Updated: 2020-02-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-01
• Study Completion Date: 2019-08-01

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.

Conditions

Spinal Cord Injuries; Venous Thromboembolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Apixaban

Apixaban 2.5 mg orally twice daily

Group Type: EXPERIMENTAL

Apixaban

Intervention Type: DRUG

2.5 mg orally twice daily

Low Molecular Weight Heparin

Either enoxaparin 40 mg or dalteparin 5000 units subcutaneously once daily

Group Type: ACTIVE_COMPARATOR

Low molecular weight heparin

Intervention Type: DRUG

Dalteparin 5000 units daily or Enoxaparin 40 mg subcutaneous daily

Interventions

Apixaban

2.5 mg orally twice daily

Intervention Type: DRUG

Low molecular weight heparin

Dalteparin 5000 units daily or Enoxaparin 40 mg subcutaneous daily

Intervention Type: DRUG

Other Intervention Names

Eliquis; Lovenox or Fragmin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Sam Schulman

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hamilton General Hospital

Hamilton, Ontario, Canada

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 27721141 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30743281 (View on PubMed)

Other Identifiers

SCI Pilot RCT

Identifier Type: -

Identifier Source: org_study_id