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

NCT04006288 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: IIS-RIVA02
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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).

Conditions

Coronary Artery Disease

Keywords

dual antiplatelet therapy; rivaroxaban; pharmacodynamic

Outcome Measures

Primary Outcomes (1)

• 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

  30 days

Study Arms (6)

Aspirin and clopidogrel

ACTIVE COMPARATOR

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

Drug: Clopidogrel; Drug: aspirin

Aspirin and rivaroxaban from aspirin and clopidogrel

EXPERIMENTAL

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

Drug: aspirin; Drug: rivaroxaban

Aspirin and prasugrel

ACTIVE COMPARATOR

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

Drug: Prasugrel; Drug: aspirin

Aspirin and rivaroxaban from aspirin and prasugrel

EXPERIMENTAL

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

Drug: aspirin; Drug: rivaroxaban

Aspirin and ticagrelor

ACTIVE COMPARATOR

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

Drug: ticagrelor; Drug: aspirin

Aspirin and rivaroxaban from aspirin and ticagrelor

EXPERIMENTAL

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

Drug: aspirin; Drug: rivaroxaban

Interventions

Clopidogrel DRUG

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

Also known as: Plavix

Aspirin and clopidogrel

Prasugrel DRUG

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

Also known as: Effient

Aspirin and prasugrel

ticagrelor DRUG

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

Also known as: brilinta

Aspirin and ticagrelor

aspirin DRUG

all patients will remain on aspirin

Aspirin and clopidogrel; Aspirin and prasugrel; Aspirin and rivaroxaban from aspirin and clopidogrel; Aspirin and rivaroxaban from aspirin and prasugrel; Aspirin and rivaroxaban from aspirin and ticagrelor; Aspirin and ticagrelor

rivaroxaban DRUG

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

Also known as: xarelto

Aspirin and rivaroxaban from aspirin and clopidogrel; Aspirin and rivaroxaban from aspirin and prasugrel; Aspirin and rivaroxaban from aspirin and ticagrelor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: lead
• Janssen, LP: collaborator

Study Sites (1)

University of Florida

Jacksonville, Florida, 32209, United States

Location

Related Publications (1)

• Ortega-Paz L, Franchi F, Rollini F, Galli M, Been L, Ghanem G, Shalhoub A, Ossi T, Rivas A, Zhou X, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Jennings LK, Angiolillo DJ. Switching from Dual Antiplatelet Therapy with Aspirin Plus a P2Y12 Inhibitor to Dual Pathway Inhibition with Aspirin Plus Vascular-Dose Rivaroxaban: The Switching Anti-Platelet and Anti-Coagulant Therapy (SWAP-AC) Study. Thromb Haemost. 2024 Mar;124(3):263-273. doi: 10.1055/a-2098-6639. Epub 2023 May 24.

  PMID: 37224883 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Clopidogrel; Prasugrel Hydrochloride; Ticagrelor; Aspirin; Rivaroxaban

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Morpholines; Oxazines

Results Point of Contact

• Title: Dr. Dominick J Angiolillo. Professor of med University of Florida College of Medicine-Jacksonville
• Organization: University of Florida

dominick.angiolillo@jax.ufl.edu

904-244-3378

Study Officials

• Dominick J Angiolillo, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: laboratory personnel running pharmacodynamic testing will be blinded to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 25, 2019
• First Posted: July 5, 2019
• Study Start: September 6, 2019
• Primary Completion: January 31, 2022
• Study Completion: May 16, 2022
• Last Updated: April 26, 2023
• Results First Posted: April 26, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)