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Trial record 95 of 509 for:    ASPIRIN AND P2

Pharmacodynamic Effects of Low-dose Rivaroxaban With Antiplatelet Therapies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03718429
Recruitment Status : Recruiting
First Posted : October 24, 2018
Last Update Posted : February 6, 2019
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE October 19, 2018
First Posted Date  ICMJE October 24, 2018
Last Update Posted Date February 6, 2019
Actual Study Start Date  ICMJE January 14, 2019
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2018)
  • Platelet aggregation measured by VerifyNow PRU [ Time Frame: 20 days ]
    P2Y12 reaction units (PRU) by VerifyNow with or without low-dose rivaroxaban in addition to each regimen of antiplatelet therapy
  • Thrombin generation [ Time Frame: 20 days ]
    Comparison of clot kinetic assessed as thrombin generation measured by Technothrombin fluorogenic assay kit with or without low-dose rivaroxaban in addition to each regimen of antiplatelet therapy
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03718429 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2018)
  • Platelet aggregation measured by VASP PRI [ Time Frame: 20 days ]
    Platelet reactivity index (PRI) by VASP with or without low-dose rivaroxaban in addition to each regimen of antiplatelet therapy
  • Clot strength [ Time Frame: 20 days ]
    Comparison of thrombus formation assessed as clot strength measured by thromboelastography with or without low-dose rivaroxaban in addition to each regimen of antiplatelet therapy
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacodynamic Effects of Low-dose Rivaroxaban With Antiplatelet Therapies
Official Title  ICMJE Pharmacodynamic Effects of Low-dose Rivaroxaban in Combination With Antiplatelet Therapies in Patients With Coronary and Peripheral Artery Disease Manifestations
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.

To date there is very little data, and not conducted in human subjects, on the interplay between anti-Xa blockade with low-dose rivaroxaban and antiplatelet therapies, and in particular how this affects profiles of platelet reactivity and thrombin generation. Given the potential role for the use of low-dose rivaroxaban for the prevention of ischemic recurrences in patients with atherothrombotic disease manifestations, including coronary artery disease (CAD) and peripheral arterial disease (PAD), the study team proposes a prospective pharmacodynamic (PD) investigation assessing the impact of low-dose rivaroxaban when used in combination with antiplatelet treatment regimens commonly used in clinical practice.

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.

However, although the introduction of newer antithrombotic strategies has been associated with a reduction in ischemic recurrences in high-risk patients, these have been consistently associated with an increase in bleeding complications. These have been observed particularly with the combination of an oral anticoagulant agent, including low-dose rivaroxaban, with standard DAPT, also known as "triple therapy". Observations from laboratory and clinical studies suggest that in the presence of effective blockade of other pathways triggering thrombotic complications aspirin may not offer added antithrombotic effects but contribute to the increased bleeding. These observations have set the basis for a large number of clinical outcomes studies evaluating whether dropping aspirin in the presence of more potent and effective blockade of other pathways triggering thrombosis has a better safety profile without a tradeoff in efficacy. Amongst these strategies, the use of low-dose rivaroxaban in adjunct to a P2Y12 inhibitor, also known as dual therapy, has been proposed. This approach may be of potential benefit to reduce atherothrombotic complications in high-risk patients following an acute coronary event. On the other hand, regimens with more modest antithrombotic effects compared with a combination of low-dose rivaroxaban and a P2Y12 receptor inhibitor such as low-dose rivaroxaban alone or in combination with aspirin may be more suitable in more stabilized patients.

To date there is very little data, and not conducted in human subjects, on the interplay between anti-Xa blockade with low-dose rivaroxaban and antiplatelet therapies, and in particular how this affects profiles of platelet reactivity and thrombin generation. Given the potential role for the use of low-dose rivaroxaban for the prevention of ischemic recurrences in patients with atherothrombotic disease manifestations, including coronary artery disease (CAD) and peripheral arterial disease (PAD), the study team proposes a prospective pharmacodynamic (PD) investigation assessing the impact of low-dose rivaroxaban when used in combination with antiplatelet treatment regimens commonly used in clinical practice.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The proposed investigation will be a prospective PD (pharmacodynamic) study conducted in cohorts of patients with CAD, PAD, or atrial fibrillation
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Coronary Artery Disease
  • Peripheral Arterial Disease
  • Atrial Fibrillation
Intervention  ICMJE Drug: Rivaroxaban 2.5Mg Tablet
PD assessments will be conducted at 3 time points: i) baseline (while on standard of care antiplatelet therapy), ii) 7-10 days after adjunctive treatment with low dose rivaroxaban, and iii) 7-10 days after dropping aspirin.
Other Name: Xarelto
Study Arms  ICMJE
  • Experimental: aspirin
    Patients will be treated with adjunctive low-dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy will be suspended for 7-10 days.
    Intervention: Drug: Rivaroxaban 2.5Mg Tablet
  • Experimental: aspirin and clopidogrel
    Patients will be treated with adjunctive low-dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy will be suspended for 7-10 days.
    Intervention: Drug: Rivaroxaban 2.5Mg Tablet
  • Experimental: aspirin and ticagrelor
    Patients will be treated with adjunctive low-dose rivaroxaban (2.5 mg/bid) for 7-10 days, after which aspirin therapy will be suspended for 7-10 days.
    Intervention: Drug: Rivaroxaban 2.5Mg Tablet
  • No Intervention: rivaroxaban
    A control cohort of subjects with atrial fibrillation on full dose rivaroxaban (20 mg/qd) as per standard of care will be recruited and will undergo a single PD assessment.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 23, 2018)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Known CAD (defined as angiographic evidence of >50% coronary artery stenosis or prior coronary revascularization) or PAD (defined as a positive ABI or prior revascularization)
  • on treatment with either aspirin (81mg/qd), aspirin (81mg/qd) plus clopidogrel (75mg/qd), or aspirin (81mg/qd) plus ticagrelor (90mg/bid) for at least 3 months per standard of care OR
  • Atrial fibrillation (paroxysmal, persistent or permanent) on treatment with rivaroxaban 20 mg qd (if CrCl >50 mL/min) or 15 mg qd (if CrCl 15 - 50 mL/min) per standard of care. Patients with concomitant CAD or PAD who are also taking antiplatelet medications are not eligible. However, if these are only on oral anticoagulation with rivaroxaban (and no antiplatelet therapy) the person will be eligible.

Exclusion criteria:

  • Active pathological bleeding, history of clinically significant bleeding events, or deemed at increased risk of bleeding.
  • CrCL <20mL/min
  • Any clinical indication to be on triple antithrombotic therapy (DAPT plus an oral anticoagulant)
  • An acute coronary event in the past 90 days
  • Prior hemorrhagic stroke or intracranial hemorrhage
  • Ischemic stroke/transient ischemic attack in the past 6 months
  • Chronic use of nonsteroidal anti-inflammatory drugs
  • On treatment with combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, and conivaptan) or inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort).
  • Known moderate or severe hepatic impairment (Child-Pugh B and C)
  • Prior hypersensitivity reaction to rivaroxaban
  • On treatment with prasugrel in the past 10 days.
  • Platelet count <80x106/mL
  • Hemoglobin <10g/dL
  • Hemodynamic instability
  • Pregnant females [women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study].
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dominick J Angiolillo, MD,PhD 904-244-3378 dominick.angiolillo@jax.ufl.edu
Contact: Andrea Goosen 904-244-5617 Andrea.Goosen@jax.ufl.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03718429
Other Study ID Numbers  ICMJE IIS-RIVA01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No sharing is planned
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE Janssen Scientific Affairs, LLC
Investigators  ICMJE
Principal Investigator: Dominick J Angiolillo, MD,PhD University of Florida
PRS Account University of Florida
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP