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Critical Limb IschemiaPhase 2RIVAL-PADNCT02260622

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

A Phase 2 study testing rivaroxaban plus aspirin and clopidogrel plus aspirin in people with Critical Limb Ischemia, run by Ottawa Hospital Research Institute at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Critical Limb Ischemia
What is being tested?
rivaroxaban plus aspirin and clopidogrel plus aspirin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteCanada
Study dates
Oct 2014to Mar 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 29Show fewer
  • 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
  • Aspirin in combination with thienopyridines within 5 days before randomization
  • Intravenous antiplatelets within 5 days before randomization
  • Fibrinolytics within 10 days before randomization
  • Known HIV infection at time of screening
  • Known significant liver disease (e.g., acute clinical hepatitis, chronic active hepatitis, cirrhosis or ALT >3ULN)
  • Childbearing potential without proper contraceptive measures, pregnancy or breast feeding
  • Drug addiction or alcohol abuse within 12 months before the randomization visit
  • Systemic treatment with strong CYP 3A4 and P-glycoprotein inhibitors : such as ketoconazole, itraconazole, posaconazole, or ritonavir
  • Known allergy or hypersensitivity to any component of rivaroxaban, ASA or clopidogrel
  • 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
  • Anticipated need for chronic (> 4 weeks) therapy with non-steroidal anti-inflammatory drugs.
  • 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.
  • Inability to adhere to protocol.
  • Severe concomitant condition or disease (e.g. life expectancy <6 months secondary to cancer, advanced liver disease or dementia)

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • The Ottawa Hospital

    Ottawa, Ontario, K1Y4E9

Other trials in Canada

About this study

Official title: 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

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).

Read more

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.

Being tested
rivaroxaban plus aspirin, clopidogrel plus aspirin
Keywords
Restenosis, Critical Limb Ischemia, Infrainguinal Percutaneous Transluminal Angioplasty, Rivaroxaban, Clopidogrel
Medical subject headings
Chronic Limb-Threatening Ischemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rivaroxaban plus aspirinDrug

    Also called treatment arm

    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

  • clopidogrel plus aspirinDrug

    Also called Plavix plus ASA, Standard Care

    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

Study groups in NCT02260622
Study groupRoleWhat they receive
clopidogrel plus aspirinActive comparatorClopidogrel 75 mg daily X 90 days plus ASA 81 mg daily
Receives: Drug: clopidogrel plus aspirin
rivaroxaban plus aspirinExperimentalRivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily
Receives: Drug: rivaroxaban plus aspirin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 1 year

Secondary outcomes (10)

  1. Number of Participants With 2 Class Improvement on the Rutherford Scale

    Clinical improvement defined as cumulative improvement of 2 classes of the Rutherford scale without the need for repeated TLR in surviving patients.

    There are seven stages to consider. the lower the score the less severe the disease or condition.

    Rutherford Scale:

    Stage 0 - Asymptomatic Stage 1 - Mild claudication Stage 2 - Moderate claudication - The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters.

    Stage 3 - Severe claudication Stage 4 - Rest pain Stage 5 - Ischemic ulceration not exceeding ulcer of the digits of the foot Stage 6 - Severe ischemic ulcers or frank gangrene

    Measured: 1 year

  2. Event-free Survival

    Event-free survival How long a patient is alive without the need for any further intervention or vascular events.

    Measured: 1 year

  3. Overall Survival

    Overall survival. How long a patient is alive following the intervention.

    Measured: 1 year

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

    Target lesion revascularization (TLR) between day 1 and final visit

    Measured: 1 year

  5. TVR

    Target vessel revascularization (TVR between day 1 and final visit)

    Measured: 1 year

  6. Peri-procedure Death

    The number of patients that die within 30 days of the revascularization procedure.

    Measured: 30 days

  7. MACE

    Cumulative rate of major adverse cardiovascular events between day 1 and final visit

    Measured: 1 year

  8. Major Bleeding

    Cumulative rate of major bleeding between day 1 and day 90

    Measured: 90 days

  9. Minor Bleeding

    Cumulative clinically relevant or minor bleeding between day 1 and day 90

    Measured: 90 days

  10. Biomarkers

    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

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2014 (estimated)
  2. Study startOct 2014
  3. Primary completionJun 2017
  4. Study completionMar 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02260622
Sponsor's protocol ID
20130484-01H
Acronym
RIVAL-PAD
Status last verified
Nov 2019
First submitted
6 Oct 2014
Last updated
4 Dec 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing rivaroxaban plus aspirin and clopidogrel plus aspirin in people with Critical Limb Ischemia, run by Ottawa Hospital Research Institute at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reintervention, Above Ankle Amputation and Restenosis (RAS) (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02260622.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2019.

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