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

NCT02260622 | Completed Phase 2 Results DMC

• 1 other identifier: 20130484-01H
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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. 1.Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily OR
2. 2.Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily

Conditions

Critical Limb Ischemia

Keywords

Restenosis; Critical Limb Ischemia; Infrainguinal Percutaneous Transluminal Angioplasty; Rivaroxaban; Clopidogrel

Outcome Measures

Primary Outcomes (1)

• Reintervention, Above Ankle Amputation and Restenosis (RAS)

  The primary outcome is a combined endpoint consisting of any Reintervention (surgical procedures to revascularize), Above ankle amputation and restenosis(recurrence of blockage in the vein) (RAS) at one year

  1 year

Secondary Outcomes (10)

• Number of Participants With 2 Class Improvement on the Rutherford Scale

  1 year

• Event-free Survival

  1 year

• Overall Survival

  1 year

• The Number of Patients Requiring Target Lesions Revascularization Between Day 1 and the Final Visit (TLR)

  1 year

• TVR

  1 year

Study Arms (2)

clopidogrel plus aspirin

ACTIVE COMPARATOR

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

Drug: clopidogrel plus aspirin

rivaroxaban plus aspirin

EXPERIMENTAL

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

Drug: rivaroxaban plus aspirin

Interventions

rivaroxaban plus aspirin 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

Also known as: treatment arm

rivaroxaban plus aspirin

clopidogrel plus aspirin 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

Also known as: Plavix plus ASA, Standard Care

clopidogrel plus aspirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Infra-inguinal PAD presenting as CLI defined as a Rutherford category of 3, 4, or 5
• More than 50% stenosis in the target infrainguinal vessel
• Good candidates for PTA using POBA (plain old balloon angioplasty) with or without stenting defined as TASC a and b lesions.

You may not qualify if:

• Rutherford scale of 0,1,2 or 6
• Acute limb-threatening ischemia (e.g. embolic disease)
• Previous infrainguinal bypass or PTA procedures of the affected leg
• Hybrid procedures
• Creatinine clearance \<30 mL/min
• Platelet count \<100x109/L
• INR \>1.5; Hbg \<100 g/L
• History of or condition associated with increased bleeding risk including, but not limited to:
• Major surgical procedure or trauma within 30 days before the randomization visit
• Clinically significant gastrointestinal bleeding within 6 months before the randomization visit
• History of intracranial, intraocular, spinal, or atraumatic intra-articular bleeding
• Chronic hemorrhagic disorder
• Known intracranial neoplasm, arteriovenous malformation, or aneurysm
• Sustained uncontrolled hypertension: systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg
• Severe, disabling stroke (modified Rankin score of 4 to 5, inclusive) within 3 months or any stroke within 14 days before the randomization visit

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• The Ottawa Hospital: collaborator

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1Y4E9, Canada

Location

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia

Interventions

Rivaroxaban; Aspirin; Clopidogrel; Standard of Care

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Penny Phillips
• Organization: Ottawa Hospital Research Institute

pphillips@ohri.ca

613-737-8899

Study Officials

• Esteban Gandara, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Prasad Jetty, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2014
• First Posted: October 9, 2014
• Study Start: October 1, 2014
• Primary Completion: June 1, 2017
• Study Completion: March 1, 2019
• Last Updated: December 4, 2019
• Results First Posted: November 22, 2019

Record last verified: 2019-11

Locations

CA (1)