Pilot Study to Examine the Use of Rivaroxaban After Angioplasty for Critical Limb Ischemia

NCT ID: NCT02260622

Last Updated: 2019-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2019-03-31

Brief Summary

Background: Up to 10% of patients with peripheral arterial disease (PAD) will develop critical limb ischemia (CLI) which is a decrease of blood flow in the arteries of the limb. CLI results in resting pain, ulcers, gangrene, and limb loss. The outcome for patients with CLI is poor. Within 3 months of onset, 12% of patients will require an amputation (removal of part of the limb) and 9% will die of major cardiovascular events (heart attack or stroke). Percutaneous angioplasty (PTA), a procedure used to open the blockages in blood flow, has become the first-line treatment for CLI given its effectiveness, lower cost, and lower risk of complications. However, 40% of patients will have re-narrowing of the arteries (restenosis) following the PTA procedure. This is thought to happen in part due to build up of blood cells called platelets which can also lead to the formation of blood clots. In order to try to avoid this problem, most patients are prescribed a combination of two blood thinning medications, acetylsalicylic acid (ASA or aspirin) and clopidogrel (the brand name is Plavix).

The purpose of this study is to determine if a new blood thinner called rivaroxaban, given in combination with aspirin, would be more effective in preventing re-narrowing of the arteries than the current standard of care (aspirin and clopidogrel).

Rivaroxaban is a pill and does not require blood test monitoring. It has been approved by Health Canada for use in prevention of blood clots in patients undergoing hip or knee surgery and to treat patients with blood clots in their legs and lungs. Low dose aspirin has been approved for reducing the risk of heart attacks and strokes. These medications have not been tested together in patients for prevention of re-narrowing of their arteries

This is a pilot study conducted at one center, The Ottawa Hospital.

It is a Phase 2 open label randomized controlled trial.

Following the PTA procedure, once all inclusion/exclusion criteria are met, the participant will be randomized into one of two groups:

1. Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily OR

2. Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily

Visits will occur at 7 days, 30 days, 90 days, 6 months and 12 months. Participants will be followed for 12 months (± 14 days) in total. All adverse events will be collected for the duration of the study.

Conditions

Critical Limb Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

clopidogrel plus aspirin

Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily

Group Type: ACTIVE_COMPARATOR

clopidogrel plus aspirin

Intervention Type: DRUG

Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days

rivaroxaban plus aspirin

Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily

Group Type: EXPERIMENTAL

rivaroxaban plus aspirin

Intervention Type: DRUG

Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days

Interventions

rivaroxaban plus aspirin

Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days

Intervention Type: DRUG

clopidogrel plus aspirin

Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days

Intervention Type: DRUG

Other Intervention Names

treatment arm; Plavix plus ASA; Standard Care

Eligibility Criteria

Inclusion Criteria

1. Written informed consent.

2. Infra-inguinal PAD presenting as CLI defined as a Rutherford category of 3, 4, or 5

3. More than 50% stenosis in the target infrainguinal vessel

4. Good candidates for PTA using POBA (plain old balloon angioplasty) with or without stenting defined as TASC a and b lesions.

Exclusion Criteria

1. Rutherford scale of 0,1,2 or 6

2. Acute limb-threatening ischemia (e.g. embolic disease)

3. Previous infrainguinal bypass or PTA procedures of the affected leg

4. Hybrid procedures

5. Creatinine clearance <30 mL/min

6. Platelet count <100x109/L

7. INR >1.5; Hbg <100 g/L

8. History of or condition associated with increased bleeding risk including, but not limited to:

1. Major surgical procedure or trauma within 30 days before the randomization visit

2. Clinically significant gastrointestinal bleeding within 6 months before the randomization visit

3. History of intracranial, intraocular, spinal, or atraumatic intra-articular bleeding

4. Chronic hemorrhagic disorder

5. Known intracranial neoplasm, arteriovenous malformation, or aneurysm

6. Sustained uncontrolled hypertension: systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg

9. Severe, disabling stroke (modified Rankin score of 4 to 5, inclusive) within 3 months or any stroke within 14 days before the randomization visit

10. Aspirin in combination with thienopyridines within 5 days before randomization

11. Intravenous antiplatelets within 5 days before randomization

12. Fibrinolytics within 10 days before randomization

13. Known HIV infection at time of screening

14. Known significant liver disease (e.g., acute clinical hepatitis, chronic active hepatitis, cirrhosis or ALT >3ULN)

15. Childbearing potential without proper contraceptive measures, pregnancy or breast feeding

16. Drug addiction or alcohol abuse within 12 months before the randomization visit

17. Systemic treatment with strong CYP 3A4 and P-glycoprotein inhibitors : such as ketoconazole, itraconazole, posaconazole, or ritonavir

18. Known allergy or hypersensitivity to any component of rivaroxaban, ASA or clopidogrel

19. Need for long term anticoagulation or double antiplatelet agents other than PAD such as atrial fibrillation, heart valve replacement, acute coronary syndrome, stroke or venous thromboembolism

20. Anticipated need for chronic (> 4 weeks) therapy with non-steroidal anti-inflammatory drugs.

21. Concomitant treatment with any other anticoagulant, including oral anticoagulants, such as warfarin, dabigatran, apixaban, except under circumstances of switching therapy to or from study treatment.

22. Inability to adhere to protocol.

23. Severe concomitant condition or disease (e.g. life expectancy <6 months secondary to cancer, advanced liver disease or dementia)

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

Sponsors

The Ottawa Hospital

OTHER

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Esteban Gandara, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Prasad Jetty, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Locations

The Ottawa Hospital

Ottawa, Ontario, Canada

Countries

Canada

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

20130484-01H

Identifier Type: -

Identifier Source: org_study_id