Rivaroxaban 2.5 mg BID and Aspirin for Intermittent Claudication in PAD Patients

Study Overview
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Brief Summary
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This trial is evaluating if rivaroxaban 2.5 mg BID and aspirin 100 mg OD compared to aspirin alone improves on intermittent claudication distance in PAD patients.

Detailed Description
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Background: The COMPASS trial demonstrated that in patients with peripheral arterial disease the combination of rivaroxaban and aspirin compared with aspirin reduces the risk of major adverse limb events, but it is not known whether this combination can also improve symptoms in patients with intermittent claudication. The primary objective of this study is to evaluate the effect of the combination on intermittent claudication distance. Study design: Eighty-eight patients with intermittent claudication will be randomized to receive rivaroxaban 2,5 mg twice daily plus aspirin 100 mg once daily or aspirin 100 mg once daily for 24 weeks. The primary outcome is the change in claudication distance from baseline to 24 hours as measured by 6 minutes walking test and treadmill test. The main safety outcome is the incidence of major bleeding according to ISTH criteria. Summary: The COMPASS CLAUDICATION trial will provide high-quality evidence regarding the effect of the combination of rivaroxaban and aspirin on claudication distance in patients with peripheral arterial disease.

Official Title
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A Prospective, Randomized, Open-label, Multicenter Study Comparing Rivaroxaban 2.5 mg Twice Daily Associated With Aspirin 100 mg Once Daily Versus Aspirin 100 mg Once Daily in Patients With Peripheral Arterial Disease and Limiting Intermittent Claudication. (The COMPASS CLAUDICATION Trial).

Conditions
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Peripheral Artery Disease, Intermittent Claudication

Intervention / Treatment
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* Drug: Rivaroxaban 2.5 Mg Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with symptomatic PAD who signed the informed consent form (ICF) with: Ankle-brachial index (ABI) < 0. 85 in at least one member, and ACD < 500 meters age > 18 years No history of lower-limbs arterial bypass surgery or angioplasties in the last year walking ability limited by the symptom of claudication and ability to complete a treadmill test Exclusion Criteria: high risk of bleeding - Evidence of a recent history of bleeding in the last three months, hemorrhagic diathesis in the last three months, changes in coagulation tests (INR> 1.5 or aPTT > 2), pulmonary bronchiectasis, active cancer, active gastroduodenal ulcer, use of dual antiplatelet therapy. Recent hemorrhagic stroke (1 month) or any history of previous hemorrhagic or lacunar stroke, if detected by occasional prior tomography, which is not part of the study protocol. severe heart failure (NYHA class III and VI) advanced stable kidney disease (estimated creatinine clearance <15 ml per minute), defined as eTFG <15 mL/min by 1.73 m2 calculated by the abbreviated formula Diet Modification in Kidney Disease (MDRD). the use of dual antiplatelet therapy, anticoagulation, or other antithrombotic therapy Continuous use of pentoxifylline or cilostazol Cardiac conditions that may lead to heart failure, such as unstable angina, arrhythmias, acute myocardial infarction in the last three months Non-cardiac conditions that may interfere with the ability to complete functional tests (e.g., chronic obstructive pulmonary disease, anemia, rheumatologic diseases) Non-cardiovascular conditions are considered by the researcher as associated with a poor prognosis. a. Active cancer with a life expectancy of fewer than six months b. Collagen limiting diseases c. Previous or scheduled surgeries that prevent functional evaluation d. Orthopedic diseases that hinder functional evaluation (j) Pregnancy. Women with the potential to bear children should be under contraceptive strategies and take a negative pregnancy test to be enrolled. (k) Patients with COVID in the contagious phase (PCR+) -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 arms, active comparator (vascular dose) versus aspirin alone
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vascular dose<br>Rivaroxaban 2.5 mg BID and aspirin 100 mg OD for 6 months | Drug: Rivaroxaban 2.5 Mg Oral Tablet<br>* oral anticoagulants plus antiplatelet agent<br>* Other names: Aspirin 100 Mg oral Tablet;|
| Active Comparator: Aspirin<br>Aspirin 100 mg OD for 6 months | Drug: Rivaroxaban 2.5 Mg Oral Tablet<br>* oral anticoagulants plus antiplatelet agent<br>* Other names: Aspirin 100 Mg oral Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial claudication distance (ICD) and the total walking distance (TWD) on 6 MWT | Improvement of the initial claudication distance (ICD) and the total walking distance (TWD) | 6 months | 
| Absolute claudication distance (ACD) on treadmill | ACD is the total distance traveled on a treadmill until it stops due to IC pain. | 6 months | 
| Quality of life Walking Impairment Questionnaire (WIQ): | A modified version of WiQ will be administered at baseline and 12 and 24 weeks | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiovascular event | Exploratory: major adverse cardiovascular events - MACE | 6 months | 
| Major adverse events of the limbs | MALE - acute limb ischemia | 6 months |