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

Atrial Fibrillation Clinical Trial

— AFIRE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02642419
• Other study ID #: AFIRE Study
• Status: Recruiting
• Phase: Phase 4
• First received: October 21, 2015
• Last updated: December 26, 2015
• Start date: January 2015
• Est. completion date: December 2017

Study information

• Verified date: December 2015
• Source: Japan Cardiovascular Research Foundation
• Contact: Saburo Saito
• Phone: +81-6-6872-0010
• Email: afire[@]jcvrf.jp
• Is FDA regulated: No
• Health authority: Japan: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2200
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

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.
• 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.

Locations

Country	Name	City	State
Japan	Japan Cardiovascular Research Foundation	Suita	Osaka

Sponsors (1)

Lead Sponsor	Collaborator
Japan Cardiovascular Research Foundation

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite endpoint of cardiovascular events	stroke, non-CNS embolism, myocardial infarction, unstable angina pectoris requiring revascularizations or all-cause mortality	mean duration: 2 years, maximum duration: 3 years	Yes
Primary	Major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria		mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	Net adverse clinical and cerebral events (NACCE)	composite of all-cause death, myocardial infarction, stroke and major bleeding.	mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	Ischemic cardiovascular events and death	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	mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	All bleeding events		mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	Adverse events excluding hemorrhagic events		mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	Comparison of the primary endpoints, ischemic cardiovascular events and mortality between patients treated with aspirin and patients treated with thienopyridine derivatives		mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	Subgroup analysis of primary endpoints, ischemic cardiovascular events and mortality according to the CHADS2 score and CHA2DS2-VASc score		mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	Subgroup analysis of primary endpoints, ischemic cardiovascular events and mortality according to subject characteristics		mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	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		mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	Comparison of the incidence of bleeding events according to whether or not proton pump inhibitors (PPIs) are used		mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	Comparison of the incidence of the primary endpoints according to whether rivaroxaban is administered in the morning or evening	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.	mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	Correlation of discontinuation of antithrombotic agents with ischemic cardiovascular events, bleeding events and adverse events		mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	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		mean duration: 2 years, maximum duration: 3 years	Yes
Secondary	The incidence of the primary endpoints according to different rates of adherence	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).	mean duration: 2 years, maximum duration: 3 years	Yes