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

• ClinicalTrials.gov Identifier: NCT04006288
• Recruitment Status: Recruiting
• First Posted: July 3, 2019
• Last Update Posted: September 10, 2019
• Sponsor: University of Florida
• Collaborator: Janssen, LP
• Information provided by (Responsible Party): University of Florida

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).

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Drug: Clopidogrel; Drug: Prasugrel; Drug: ticagrelor; Drug: aspirin; Drug: rivaroxaban	Phase 4

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 6, 2019
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: April 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Aspirin and clopidogrel; aspirin 81 mg/qd plus clopidogrel 75mg/qd for 30 days	Drug: Clopidogrel; Patients on aspirin and plavix will be randomized to either continue with aspirin and plavix or to switch to aspirin and rivaroxaban; Other Name: Plavix; Drug: aspirin; all patients will remain on aspirin
Experimental: Aspirin and rivaroxaban from aspirin and clopidogrel; aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days	Drug: aspirin; all patients will remain on aspirin; Drug: rivaroxaban; Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban; Other Name: xarelto
Active Comparator: Aspirin and prasugrel; aspirin 81 mg/qd plus prasugrel 10mg/qd for 30 days	Drug: Prasugrel; Patients on aspirin and prasugrel will be randomized to either continue with aspirin and prasugrel or to switch to aspirin and rivaroxaban; Other Name: Effient; Drug: aspirin; all patients will remain on aspirin
Experimental: Aspirin and rivaroxaban from aspirin and prasugrel; aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days	Drug: aspirin; all patients will remain on aspirin; Drug: rivaroxaban; Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban; Other Name: xarelto
Active Comparator: Aspirin and ticagrelor; aspirin 81 mg/qd plus ticagrelor 60mg/bid for 30 days	Drug: ticagrelor; Patients on aspirin and ticagrelor will be randomized to either continue with aspirin and ticagrelor or to switch to aspirin and rivaroxaban; Other Name: brilinta; Drug: aspirin; all patients will remain on aspirin
Experimental: Aspirin and rivaroxaban from aspirin and ticagrelor; aspirin 81mg/qd plus rivaroxaban 2.5mg/bid for 30 days	Drug: aspirin; all patients will remain on aspirin; Drug: rivaroxaban; Patients on DAPT will be randomized to either continue with DAPT or to switch to aspirin and rivaroxaban; Other Name: xarelto

Outcome Measures

Primary Outcome Measures :

1. Maximal platelet aggregation (MPA%) by light transmittance aggregometry (LTA) [ Time Frame: 30 days ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Dominick J Angiolillo, MD, PhD; 9042443378; dominick.angiolillo@jax.ufl.edu

Contact: Andrea Goosen, RN; 9042445617; andrea.goosen@jax.ufl.edu

Locations

United States, Florida

University of Florida; Recruiting

Jacksonville, Florida, United States, 32209

Contact: Dominick J Angiolillo, MD, PhD dominick.angiolillo@jax.ufl.edu

Principal Investigator: Dominick J Angiolillo, MD, PhD

Sponsors and Collaborators

University of Florida

Janssen, LP

Investigators

• Principal Investigator: Dominick J Angiolillo, MD, PhD; University of Florida

More Information

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT04006288 History of Changes
• Other Study ID Numbers: IIS-RIVA02
• First Posted: July 3, 2019
• Last Update Posted: September 10, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Florida:

dual antiplatelet therapy; rivaroxaban; pharmacodynamic

Additional relevant MeSH terms:

Myocardial Ischemia; Aspirin; Clopidogrel; Coronary Artery Disease; Coronary Disease; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Rivaroxaban; Ticagrelor; Prasugrel Hydrochloride; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists