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Pilot Study to Examine the Use of Rivaroxaban After Angioplasty for Critical Limb Ischemia (RIVAL-PAD)

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ClinicalTrials.gov Identifier: NCT02260622
Recruitment Status : Completed
First Posted : October 9, 2014
Last Update Posted : July 22, 2019
Sponsor:
Collaborator:
The Ottawa Hospital
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Tracking Information
First Submitted Date  ICMJE October 6, 2014
First Posted Date  ICMJE October 9, 2014
Last Update Posted Date July 22, 2019
Study Start Date  ICMJE October 2014
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
RAS [ Time Frame: 1 year ]
The primary outcome is a combined endpoint consisting of any Reintervention, Above ankle amputation and restenosis (RAS) at one year
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02260622 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
  • Improved Rutherford Scale [ Time Frame: 1 year ]
    Clinical improvement defined as cumulative improvement of 2 classes of the Rutherford scale without the need for repeated TLR in surviving patients.
  • Event-free survival [ Time Frame: 1 year ]
    Event-free survival
  • Overall survival [ Time Frame: 1 year ]
    Overall survival
  • TLR [ Time Frame: 1 year ]
    Target lesion revascularization (TLR) between day 1 and final visit
  • TVR [ Time Frame: 1 year ]
    Target vessel revascularization (TVR between day 1 and final visit)
  • Peri-procedure death [ Time Frame: 30 days ]
    Peri-procedure death within 30 days
  • MACE [ Time Frame: 1 year ]
    Cumulative rate of major adverse cardiovascular events between day 1 and final visit
  • Major Bleeding [ Time Frame: 90 days ]
    Cumulative rate of major bleeding between day 1 and day 90
  • Minor Bleeding [ Time Frame: 90 days ]
    Cumulative clinically relevant or minor bleeding between day 1 and day 90
  • Biomarkers [ Time Frame: 90 days ]
    Biological plausibility by measuring coagulation changes and SMC proliferation markers within 7 and 90 days based on the following markers: D-dimer, soluble CD40/44 ligands, and ERK 1/2
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study to Examine the Use of Rivaroxaban After Angioplasty for Critical Limb Ischemia
Official Title  ICMJE A Phase 2, Open Label, Pilot Study to Examine the Use of Rivaroxaban Plus Aspirin vs. Clopidogrel Plus Aspirin for the Prevention of Restenosis After Infrainguinal Percutaneous Transluminal Angioplasty for Critical Limb Ischemia
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Critical Limb Ischemia
Intervention  ICMJE
  • Drug: 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
    Other Name: treatment arm
  • 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
    Other Names:
    • Plavix plus ASA
    • Standard Care
Study Arms  ICMJE
  • Active Comparator: clopidogrel plus aspirin
    Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily
    Intervention: Drug: clopidogrel plus aspirin
  • Experimental: rivaroxaban plus aspirin
    Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily
    Intervention: Drug: rivaroxaban plus aspirin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 17, 2016)
20
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2014)
40
Actual Study Completion Date  ICMJE March 2019
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02260622
Other Study ID Numbers  ICMJE 20130484-01H
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ottawa Hospital Research Institute
Study Sponsor  ICMJE Ottawa Hospital Research Institute
Collaborators  ICMJE The Ottawa Hospital
Investigators  ICMJE
Principal Investigator: Esteban Gandara, MD Ottawa Hospital Research Institute
Principal Investigator: Prasad Jetty, MD Ottawa Hospital Research Institute
PRS Account Ottawa Hospital Research Institute
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP