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

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).

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.

Study Overview

• Status: Completed
• Conditions: Intermittent Claudication; Peripheral Artery Disease
• Intervention / Treatment: Drug: Rivaroxaban 2.5 Mg Oral Tablet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Santo André, São Paulo, Brazil, 09030370
      • Science Valley Research Institute
    • Santo André, São Paulo, Brazil, 09030-010
      • Hospital e Maternidade Christovão da Gama - Science Valley clinical site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with symptomatic PAD who signed the informed consent form (ICF) with:

  1. Ankle-brachial index (ABI) < 0. 85 in at least one member, and
  2. ACD < 500 meters
  3. age > 18 years
  4. No history of lower-limbs arterial bypass surgery or angioplasties in the last year
  5. walking ability limited by the symptom of claudication and
  6. ability to complete a treadmill test

Exclusion Criteria:

1. 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.

2. 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.
3. severe heart failure (NYHA class III and VI)
4. 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).
5. the use of dual antiplatelet therapy, anticoagulation, or other antithrombotic therapy
6. Continuous use of pentoxifylline or cilostazol
7. Cardiac conditions that may lead to heart failure, such as unstable angina, arrhythmias, acute myocardial infarction in the last three months
8. Non-cardiac conditions that may interfere with the ability to complete functional tests (e.g., chronic obstructive pulmonary disease, anemia, rheumatologic diseases)
9. 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+)

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the total walking distance (TWD) at week 24 in meters in the 6-Minute Walk Test (6MWT)	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the total walking distance (TWD) at week 24 in meters in the treadmill test (TMT)	6 months
Change from baseline in the Quality of Life Walking Impairment Questionnaire (WIQ) from at week 24	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiovascular events (MACE)	Exploratory Efficacy Outcome	6 months
Major Adverse Limb Events (MALE)	Exploratory Efficacy Outcome	6 months
Major or clinically non-relevant bleeding defined according to the International Society of Thrombosis and Hemostasis (ISTH) criteria	Primary Safety Outcome	6 months

Collaborators and Investigators

• Sponsor: Science Valley Research Institute
• Collaborators: Bayer

Publications and helpful links

General Publications

• Ramacciotti E, Agati LB, Volpiani GG, Brito KF, Ribeiro CM, Aguiar VCR, Ramacciotti LS, Paganotti A, Pereira FM, Caffaro RA, Fioranelli A, Krakauer R, Rached HRS, Wolosker N, Anand SS, Eikelboom JW, Lopes RD. Rivaroxaban with Aspirin Versus Aspirin for Peripheral Arterial Disease and Intermittent Claudication. Rationale and Design of the COMPASS CLAUDICATION Trial. Clin Appl Thromb Hemost. 2022 Jan-Dec;28:10760296211073922. doi: 10.1177/10760296211073922.

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2021
• Primary Completion (Actual): November 1, 2022
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 17, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Vascular Diseases; Peripheral Arterial Disease; Intermittent Claudication; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: ScienceValley

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data is collected on RedCap, thast allows open and sharing IPD
• IPD Sharing Time Frame: 1 year
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No