Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study (AFIRE)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02642419
Recruitment Status : Unknown
Verified December 2015 by Japan Cardiovascular Research Foundation.
Recruitment status was:  Recruiting
First Posted : December 30, 2015
Last Update Posted : December 30, 2015
Sponsor:
Information provided by (Responsible Party):
Japan Cardiovascular Research Foundation

Brief Summary:

In patients with atrial fibrillation (AF) complicated with coronary artery disease (CAD), antiplatelet drugs are commonly used for the prevention of recurrence of stent thrombosis and cardiovascular events in combination with anticoagulant drugs. Based on the observations that the incidence of hemorrhagic complications increased when an antiplatelet drug was administered in combination with vitamin K antagonist (VKA), the guidelines for antithrombotic therapy after PCI in the US and EU recommend that DAPT (dual anti-platelets therapy) should be used in AF-complicated CAD patients for as short a time as possible following single anti-platelet and VKA, and that monotherapy with VKA should be started from one year after PCI. In 2013 the European Heart Rhythm Association (EHRA) published the guidelines for the use of NOACs in NVAF patients, which state that NOACs may have advantage to VKAs in terms of anti-thrombotic effects in NVAF patients undergoing PCI. However, no clinical evidence has ever been generated to reveal the efficacy and safety of mono-drug therapy with a NOACs in stable CAD patients one year or more after PCI.

AFIRE study is planned to evaluate the efficacy and safety of mono-drug therapy with a rivaroxaban in stable CAD patients. Among NOACs, rivaroxaban was chosen because of the evidence in Japanese patients and the results of a sub-analysis of ROCKET AF suggesting that rivaroxaban is more effective than VKA in reducing the incidence of myocardial infarction (MI).


Condition or disease Intervention/treatment Phase
Atrial Fibrillation Drug: Rivaroxaban and single antiplatelet drug (aspirin, clopidogrel or prasugrel) Drug: Rivaroxaban Phase 4

Detailed Description:

Study Design:prospective, randomized, open-label trial

Allocation:ratio to rivaroxaban monotherapy and rivaroxaban in co-administration with a single anti-platelet therapy is 1: 1 using WEB system


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study (AFIRE Study)
Study Start Date : January 2015
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Rivaroxaban

Arm Intervention/treatment
Experimental: Rivaroxaban Drug: Rivaroxaban
Rivaroxaban will be orally administered at a dose of 15 mg if the creatinine clearance (CLcr) is 50 mL/min or more and at a dose of 10 mg if the CLcr is 15-49 mL/min.

Experimental: Rivaroxaban and single antiplatelet drug Drug: Rivaroxaban and single antiplatelet drug (aspirin, clopidogrel or prasugrel)
  • Rivaroxaban will be orally administered after a meal at a dose of 15 mg if the creatinine clearance (CLcr) is 50 mL/min or more and at a dose of 10 mg if the CLcr is 15-49 mL/min (regardless of time)
  • Antiplatelet will be selected from aspirin or thienopyridine derivatives (clopidogrel or prasugrel)

    • Aspirin will be orally administered once a day at a dose of 81 mg or 100 mg
    • Clopidogrel will be orally administered once a day after a meal at a dose of 75 mg. The dose will be reduced to 50mg once a day depending on age, body weight or clinical findings.
    • Prasugrel will be orally administered once a day at a dose of 3.75 mg. If the body weight is 50kg or less a reduced dose(2.5 mg once a day) will be considered depending on the age, renal function or other bleeding and thrombotic risk.




Primary Outcome Measures :
  1. Composite endpoint of cardiovascular events [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
    stroke, non-CNS embolism, myocardial infarction, unstable angina pectoris requiring revascularizations or all-cause mortality

  2. Major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]

Secondary Outcome Measures :
  1. Net adverse clinical and cerebral events (NACCE) [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
    composite of all-cause death, myocardial infarction, stroke and major bleeding.

  2. Ischemic cardiovascular events and death [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
    • All-cause mortality
    • Cardiovascular death
    • non-cardiovascular death
    • Myocardial infarction
    • Unstable angina pectoris requiring revascularization
    • Ischemic stroke
    • Transient ischemic attack
    • non-CNS embolism (systemic embolism pulmonary embolism, deep vein thrombosis)
    • PCI/CABG
    • Stent thrombosis
    • Ischemic stroke and systemic embolism

  3. All bleeding events [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
  4. Adverse events excluding hemorrhagic events [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
  5. Comparison of the primary endpoints, ischemic cardiovascular events and mortality between patients treated with aspirin and patients treated with thienopyridine derivatives [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
  6. Subgroup analysis of primary endpoints, ischemic cardiovascular events and mortality according to the CHADS2 score and CHA2DS2-VASc score [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
  7. Subgroup analysis of primary endpoints, ischemic cardiovascular events and mortality according to subject characteristics [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
  8. Subgroup analysis of major bleeding and all bleeding events according to the HAS-BLED score in patients with and without co-administration of antiplatelet drug and analysis of specificity and sensitivity [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
  9. Comparison of the incidence of bleeding events according to whether or not proton pump inhibitors (PPIs) are used [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
  10. Comparison of the incidence of the primary endpoints according to whether rivaroxaban is administered in the morning or evening [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
    Primary endpoints include the composite endpoint of cardiovascular events (stroke, non-CNS embolism, myocardial infarction, unstable angina pectoris requiring revascularization or cardiovascular death) and major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria.

  11. Correlation of discontinuation of antithrombotic agents with ischemic cardiovascular events, bleeding events and adverse events [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
  12. Correlation of prothrombin time at trough with bleeding events and evaluation of the cutoff values in patients with and without co-administration of antiplatelet drug [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]
  13. The incidence of the primary endpoints according to different rates of adherence [ Time Frame: mean duration: 2 years, maximum duration: 3 years ]

    Primary endpoints include the composite endpoint of cardiovascular events (stroke, non-CNS embolism, myocardial infarction, unstable angina pectoris requiring revascularization or cardiovascular death) and major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria.

    The rate of adherence will be calculated by dividing the number of prescribed tablets by the period of treatment: e.g., if 240 tablets are prescribed for 300 days, the rate of adherence will be 80.0% (240/300).




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients with non-valvular atrial fibrillation complicated with stable coronary artery disease who are 20 years or older, with CHADS2 score are ≧1 , and that fulfill one of the following criteria and can provide written consent for participation in the present study will be eligible.

  1. Patients who underwent percutaneous coronary intervention(PCI), including plain old balloon angioplasty(POBA), at least one year ago
  2. Patients who have coronary stenosis requiring no percutaneous coronary intervention (50% or more stenosis) as indicated by coronary CT or coronary angiography(CAG)
  3. Patients who underwent coronary artery bypass graft (CABG) at least one year ago

Exclusion Criteria:

  • Patients for whom rivaroxaban is contraindicated
  • Patients for whom aspirin, thienopyridine derivatives (clopidogrel or prasugrel) are contraindicated
  • Patients who underwent PCI, including POBA, in the past one year
  • Patients who are going to undergo revascularization
  • Patients who have a past history of stent thrombosis
  • Those who are going to undergo invasive surgery (excluding digestive endoscopy and biopsy)
  • Patients who have active tumors
  • Patients who have poorly-controlled hypertension (systolic blood pressure at hospital admission: 160 mmHg or more)
  • Patients who cannot discontinue treatment with antiplatelet drugs (the physician in charge will make a decision on the basis of the lesion shape, lesion site and type of stents.)
  • Patients judged as inappropriate for this study by investigators

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02642419


Contacts
Layout table for location contacts
Contact: Saburo Saito +81-6-6872-0010 afire@jcvrf.jp

Locations
Layout table for location information
Japan
Japan Cardiovascular Research Foundation Recruiting
Suita, Osaka, Japan, 565-8565
Contact: Hisao Ogawa    +81-6-6833-8706    ogawah@ncvc.go.jp   
Principal Investigator: Hisao Ogawa, M.D.         
Sponsors and Collaborators
Japan Cardiovascular Research Foundation
Investigators
Layout table for investigator information
Principal Investigator: Hisao Ogawa Japan Cardiovascular Research Foundation

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Japan Cardiovascular Research Foundation
ClinicalTrials.gov Identifier: NCT02642419     History of Changes
Other Study ID Numbers: AFIRE Study
First Posted: December 30, 2015    Key Record Dates
Last Update Posted: December 30, 2015
Last Verified: December 2015
Additional relevant MeSH terms:
Layout table for MeSH terms
Atrial Fibrillation
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Aspirin
Rivaroxaban
Clopidogrel
Prasugrel Hydrochloride
Platelet Aggregation Inhibitors
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
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics