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Switching From DAPT to Dual Pathway Inhibition With Low-dose Rivaroxaban in Adjunct to Aspirin in Patients With Coronary Artery Disease (SWAP-AC)

Primary Purpose

Coronary Artery Disease

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Clopidogrel

Prasugrel

ticagrelor

aspirin

rivaroxaban

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring dual antiplatelet therapy, rivaroxaban, pharmacodynamic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Willing and able to provide written informed consent
Above 18 years of age
Have known CAD and have completed their required duration of standard of care DAPT (aspirin in combination with either clopidogrel, prasugrel, or ticagrelor) and still be on treatment:
- ≥ 6 months after an elective PCI
- ≥ 12 months after experiencing an ACS (irrespective of revascularization at the time of ACS; thus patients treated by PCI, CABG, or medically managed can be considered)

Exclusion criteria:

Deemed to be at high risk of bleeding, active bleeding or history of major bleeding Stroke within 1 month or any history of hemorrhagic or lacunar stroke
Estimated glomerular filtration rate <15 mL/min by MDRD equation
Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy, or oral anticoagulant therapy
Known non-cardiovascular disease that is associated with poor prognosis (e.g., metastatic cancer) or that increases the risk of an adverse reaction to study interventions.
History of hypersensitivity or known contraindication for rivaroxaban.
Systemic treatment with strong inhibitors of both CYP 3A4 and p-glycoprotein (e.g., systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus [HIV]-protease inhibitors, such as ritonavir), or strong inducers of CYP 3A4, i.e.

rifampicin, rifabutin, phenobarbital, phenytoin, and carbamazepine

Any known hepatic disease associated with coagulopathy
Subjects who are pregnant, breastfeeding, or are of childbearing potential, and sexually active and not practicing an effective method of birth control (e.g. surgically sterile, prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive patch, male partner sterilization)
Concomitant participation in another study with investigational drug
Known contraindication to any study related procedures
Hemoglobin ≤9 mg/dL
Platelet count <80x106/mL

Sites / Locations

University of Florida

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Arm Label

Aspirin and clopidogrel

Aspirin and rivaroxaban from aspirin and clopidogrel

Aspirin and prasugrel

Aspirin and rivaroxaban from aspirin and prasugrel

Aspirin and ticagrelor

Aspirin and rivaroxaban from aspirin and ticagrelor

Arm Description

aspirin 81 mg/qd plus clopidogrel 75mg/qd for 30 days

aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days

aspirin 81 mg/qd plus prasugrel 10mg/qd for 30 days

aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days

aspirin 81 mg/qd plus ticagrelor 60mg/bid for 30 days

aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days

Outcomes

Primary Outcome Measures

Maximal Platelet Aggregation (MPA%) by Light Transmittance Aggregometry (LTA)

The primary end point of this study will be the comparison of MPA% measured by LTA using the CATF cocktail as agonist between DAPT and low-dose rivaroxaban plus aspirin for each DAPT regimen

Secondary Outcome Measures

Full Information

NCT ID

NCT04006288

First Posted

June 25, 2019

Last Updated

April 25, 2023

Sponsor

University of Florida

Collaborators

Janssen, LP

1. Study Identification

Unique Protocol Identification Number

NCT04006288

Brief Title

Switching From DAPT to Dual Pathway Inhibition With Low-dose Rivaroxaban in Adjunct to Aspirin in Patients With Coronary Artery Disease

Acronym

SWAP-AC

Official Title

Switching From Standard of Care Dual Antiplatelet Treatment (DAPT) Regimens With Aspirin Plus a P2Y12 Inhibitor to Dual Pathway Inhibition (DPI) With Low-dose Rivaroxaban in Adjunct to Aspirin in Patients With Coronary Artery Disease: The Switching Anti-Platelet and Anti-Coagulant Therapy (SWAP-AC) Study

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Completed

Study Start Date

September 6, 2019 (Actual)

Primary Completion Date

January 31, 2022 (Actual)

Study Completion Date

May 16, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Florida

Collaborators

Janssen, LP

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Recent studies indicate that anti-factor-Xa inhibition with low-dose rivaroxaban may have a role in the reduction of ischemic recurrences in patients with atherosclerotic disease manifestations. The objectives of this investigation are to assess the feasibility of switching from a DAPT to DPI regimen and to compare the pharmacodynamic profiles of these treatment regimens. This will be a prospective study conducted in cohorts of patients with CAD on treatment per standard of care with DAPT. Patients will be randomized to either maintain DAPT or to DPI. DPI consists in treatment with aspirin (81mg/qd) plus rivaroxaban (2.5mg/bid).

Detailed Description

Recent studies indicate that anti-factor-Xa inhibition with low-dose rivaroxaban may have a role in the reduction of ischemic recurrences in patients with atherosclerotic disease manifestations. In the COMPASS trial, patients with stable coronary or peripheral artery disease and no indication for oral anticoagulation or dual antiplatelet therapy (DAPT) were randomized to rivaroxaban 2.5 mg bid in combination with aspirin, rivaroxaban 5 mg bid monotherapy or aspirin monotherapy. The study showed a significant 24% relative reduction in ischemic outcomes with rivaroxaban 2.5 mg bid plus aspirin combination strategy compared with aspirin alone. These observations have raised practical considerations on how to implement the results of the COMPASS trial in clinical practice particularly for patients who are completing a minimum duration of DAPT and contemplating between continuing with a DAPT regimen versus switching to a dual pathway inhibition (DPI) regimen with aspirin plus rivaroxaban. Therefore, the objectives of this investigation are to assess the feasibility of switching from a DAPT to DPI regimen and to compare the pharmacodynamic profiles of these treatment regimens. This will be a prospective study conducted in cohorts of patients with CAD on treatment per standard of care with DAPT. Patients will be randomized to either maintain DAPT or to DPI. DPI consists in treatment with aspirin (81mg/qd) plus rivaroxaban (2.5mg/bid).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Coronary Artery Disease

Keywords

dual antiplatelet therapy, rivaroxaban, pharmacodynamic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

Patients treated with either aspirin (81mg/qd) plus clopidogrel, aspirin (81mg/qd) plus ticagrelor (90mg/bid), or aspirin (81mg/qd) plus prasugrel (10mg/bid) will be identified. Each cohort will be randomized 1:1 to either maintain DAPT or to DPI. DPI consists in treatment with aspirin (81mg/qd) plus rivaroxaban (2.5mg/bid). Patients randomized to DAPT will continue their guideline recommended DAPT regimens.

Masking

None (Open Label)

Masking Description

laboratory personnel running pharmacodynamic testing will be blinded to treatment assignment.

Allocation

Randomized

Enrollment

90 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Aspirin and clopidogrel

Arm Type

Active Comparator

Arm Description

aspirin 81 mg/qd plus clopidogrel 75mg/qd for 30 days

Arm Title

Aspirin and rivaroxaban from aspirin and clopidogrel

Arm Type

Experimental

Arm Description

aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days

Arm Title

Aspirin and prasugrel

Arm Type

Active Comparator

Arm Description

aspirin 81 mg/qd plus prasugrel 10mg/qd for 30 days

Arm Title

Aspirin and rivaroxaban from aspirin and prasugrel

Arm Type

Experimental

Arm Description

aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days

Arm Title

Aspirin and ticagrelor

Arm Type

Active Comparator

Arm Description

aspirin 81 mg/qd plus ticagrelor 60mg/bid for 30 days

Arm Title

Aspirin and rivaroxaban from aspirin and ticagrelor

Arm Type

Experimental

Arm Description

aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days

Intervention Type

Drug

Intervention Name(s)

Clopidogrel

Other Intervention Name(s)

Plavix

Intervention Description

Patients on aspirin and plavix will be randomized to either continue with aspirin and plavix or to switch to aspirin and rivaroxaban

Intervention Type

Drug

Intervention Name(s)

Prasugrel

Other Intervention Name(s)

Effient

Intervention Description

Patients on aspirin and prasugrel will be randomized to either continue with aspirin and prasugrel or to switch to aspirin and rivaroxaban

Intervention Type

Drug

Intervention Name(s)

ticagrelor

Other Intervention Name(s)

brilinta

Intervention Description

Patients on aspirin and ticagrelor will be randomized to either continue with aspirin and ticagrelor or to switch to aspirin and rivaroxaban

Intervention Type

Drug

Intervention Name(s)

aspirin

Intervention Description

all patients will remain on aspirin

Intervention Type

Drug

Intervention Name(s)

rivaroxaban

Other Intervention Name(s)

xarelto

Intervention Description

Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban

Primary Outcome Measure Information:

Title

Maximal Platelet Aggregation (MPA%) by Light Transmittance Aggregometry (LTA)

Description

The primary end point of this study will be the comparison of MPA% measured by LTA using the CATF cocktail as agonist between DAPT and low-dose rivaroxaban plus aspirin for each DAPT regimen

Time Frame

30 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Willing and able to provide written informed consent Above 18 years of age Have known CAD and have completed their required duration of standard of care DAPT (aspirin in combination with either clopidogrel, prasugrel, or ticagrelor) and still be on treatment: ≥ 6 months after an elective PCI ≥ 12 months after experiencing an ACS (irrespective of revascularization at the time of ACS; thus patients treated by PCI, CABG, or medically managed can be considered) Exclusion criteria: Deemed to be at high risk of bleeding, active bleeding or history of major bleeding Stroke within 1 month or any history of hemorrhagic or lacunar stroke Estimated glomerular filtration rate <15 mL/min by MDRD equation Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy, or oral anticoagulant therapy Known non-cardiovascular disease that is associated with poor prognosis (e.g., metastatic cancer) or that increases the risk of an adverse reaction to study interventions. History of hypersensitivity or known contraindication for rivaroxaban. Systemic treatment with strong inhibitors of both CYP 3A4 and p-glycoprotein (e.g., systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus [HIV]-protease inhibitors, such as ritonavir), or strong inducers of CYP 3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin, and carbamazepine Any known hepatic disease associated with coagulopathy Subjects who are pregnant, breastfeeding, or are of childbearing potential, and sexually active and not practicing an effective method of birth control (e.g. surgically sterile, prescription oral contraceptives, contraceptive injections, intrauterine device, double barrier method, contraceptive patch, male partner sterilization) Concomitant participation in another study with investigational drug Known contraindication to any study related procedures Hemoglobin ≤9 mg/dL Platelet count <80x106/mL

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dominick J Angiolillo, MD, PhD

Organizational Affiliation

University of Florida

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Florida

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32209

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Switching From DAPT to Dual Pathway Inhibition With Low-dose Rivaroxaban in Adjunct to Aspirin in Patients With Coronary Artery Disease

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