Optimizing Antithrombotic Care in Patients With AtriaL fibrillatiON and Coronary stEnt (OAC-ALONE) Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Kyoto University, Graduate School of Medicine
Sponsor:
Collaborators:
Research Institute for Production Development
Daiichi Sankyo Co., Ltd.
Information provided by (Responsible Party):
Satoshi Shizuta, Kyoto University, Graduate School of Medicine
ClinicalTrials.gov Identifier:
NCT01962545
First received: October 5, 2013
Last updated: May 31, 2015
Last verified: May 2015
  Purpose

The purpose of the study is to evaluate non-inferiority of oral anticoagulant (OAC) monotherapy to OAC plus single antiplatelet therapy (APT) in patients with atrial fibrillation (AF) and prior (>12 months) coronary stenting.


Condition Intervention Phase
Atrial Fibrillation
Coronary Artery Disease
Drug: OAC alone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Optimizing Antithrombotic Care in Patients With AtriaL fibrillatiON and Coronary stEnt (OAC-ALONE) Study

Resource links provided by NLM:


Further study details as provided by Kyoto University, Graduate School of Medicine:

Primary Outcome Measures:
  • The primary endpoint of this study is a composite of all-caused death, myocardial infarction, and stroke or systemic embolism. [ Time Frame: Day-0 to the day when the finally enrolled patient complete 1-year follow-up (anticipated mean duration: 2.5-year). ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Stent thrombosis. [ Time Frame: Day-0 to the day when the finally enrolled patient complete 1-year follow-up (anticipated mean duration: 2.5-year). ] [ Designated as safety issue: Yes ]
    Stent thrombosis.

  • Myocardial infarction. [ Time Frame: Day-0 to the day when the finally enrolled patient complete 1-year follow-up (anticipated mean duration: 2.5-year). ] [ Designated as safety issue: Yes ]
    One of the individual components of the primary endpoint.

  • Stroke or systemic embolism. [ Time Frame: Day-0 to the day when the finally enrolled patient complete 1-year follow-up (anticipated mean duration: 2.5-year). ] [ Designated as safety issue: Yes ]
    One of the individual components of the primary endpoint.

  • All-caused death. [ Time Frame: Day-0 to the day when the finally enrolled patient complete 1-year follow-up (anticipated mean duration: 2.5-year). ] [ Designated as safety issue: Yes ]
    One of the individual components of the primary endpoint.

  • Major bleeding. [ Time Frame: Day-0 to the day when the finally enrolled patient complete 1-year follow-up (anticipated mean duration: 2.5-year). ] [ Designated as safety issue: Yes ]
  • Cardiovascular death. [ Time Frame: Day-0 to the day when the finally enrolled patient complete 1-year follow-up (anticipated mean duration: 2.5-year). ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 2000
Study Start Date: October 2013
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OAC alone
OAC includes warfarin or NOAC. The dose of warfarin should be adjusted with the target international normalized ratio (INR) range of 2.0-3.0 for those <70 years and 1.6-2.6 for those =>70 years, which is recommended in the Japanese guidelines. NOAC includes dabigatran 150mg or 110mg twice daily, rivaroxaban 15mg daily with the reduced dose of 10mg daily, apixaban 5mg twice daily with the reduced dose of 2.5mg twice daily, and edoxaban 60mg daily with the reduced dose of 30mg daily.
Drug: OAC alone
Single APT with either aspirin or clopidogrel is discontinued in this arm.
No Intervention: OAC plus single APT

OAC includes warfarin or NOAC. The dose of warfarin should be adjusted with the target INR range of 2.0-3.0 for those <70 years and 1.6-2.6 for those =>70 years, which is recommended in the Japanese guidelines. NOAC includes dabigatran 150mg or 110mg twice daily, rivaroxaban 15mg daily with the reduced dose of 10mg daily, apixaban 5mg twice daily with the reduced dose of 2.5mg twice daily, and edoxaban 60mg daily with the reduced dose of 30mg daily.

Single APT includes aspirin or clopidogrel. The dose of aspirin is 81-324mg/day and the dose of clopidogrel is 75mg/day.


Detailed Description:

It has been reported that 5-10% of patients undergoing percutaneous coronary intervention (PCI) have concomitant AF. Most of those patients have an indication for OAC therapy to prevent stroke or systemic thromboembolism, and also for APT to prevent ischemic cardiac events, particularly myocardial infarction (MI) due to stent thrombosis (ST). However, combined use of OAC and APT is associated with increased risk of major bleeding. Thus, we need to balance the risk for stroke or systemic thromboembolism and coronary events against the risk for bleeding complications.

The AF guidelines of European Society of Cardiology (ESC) published in 2010 recommended vitamin-K antagonist (VKA) monotherapy as life-long antithrombotic therapy after 12 months of combined use of VKA plus APT in AF patients undergoing coronary stenting. Single APT with either aspirin or clopidogrel is the commonly used APT regimen in non-AF patients beyond 1-year after PCI-stenting. No APT coverage after coronary stenting was reported to be associated with increased risk for ST. It has not yet been thoroughly clarified whether VKA monotherapy is equally effective as single APT in the prevention of ST, although several RCTs have shown that VKA was more effective than aspirin for the secondary prevention of ischemic cardiac events in post-MI patients mostly untreated with coronary stent, and recent observational studies have suggested the safety of VKA monotherapy beyond 1-year after PCI-stenting. Nevertheless, there have been no RCTs focusing the safety of VKA monotherapy for AF patients in the chronic phase of PCI-stenting.

Also, because phase-3 RCTs comparing warfarin and non-VKA OAC (NOAC) in the prevention of stroke or systemic embolism in AF patients showed no significant difference in the incidence of MI during follow-up, the consensus document of ESC published in 2014 recommended OAC monotherapy with either VKA or NOAC as life-long antithrombotic therapy beyond 1-year after coronary stenting for AF patients. However, there have been no RCTs or observational studies demonstrating the safety of NOAC alone beyond 1-year after PCI-stenting.

Accordingly, we planned a prospective randomized controlled open label trial comparing OAC alone versus OAC plus single APT in AF patients beyond 1-year after PCI-stenting. AF patients receiving OAC with either warfarin or NOAC in combination with single APT with either aspirin or clopidogrel, who underwent PCI-stenting more than 12 months ago, are eligible for the study. Patients are randomly assigned to OAC alone (intervention arm, discontinuing single APT) or OAC plus single APT (control arm, no change in antithrombotic therapy).

The patient enrollment period is approximately 3 years and follow-up duration is at least 1 year. Therefore, the anticipated mean follow-up duration is approximately 2.5-year.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with a documented history of AF who underwent PCI with stenting >12 months before enrollment.
  2. Patients who are treated with OAC (warfarin or NOAC) and an antiplatelet drug (aspirin or clopidogrel), but not with other antiplatelet drugs including ticlopidine, prasugrel, ticagrelor, and cilostazol.
  3. In patients treated with warfarin, the INR value at enrollment should be => 1.6, and agreement on dose adjustment of warfarin with the target INR range of 2.0-3.0 for those <70 years and 1.6-2.6 for those =>70 years, which is recommended in the Japanese guidelines, is necessary before enrollment.
  4. Patients 20 years or older.
  5. Patients with written informed consent.

Exclusion Criteria:

  1. Patients who underwent PCI including balloon angioplasty alone within the past 12 months.
  2. Patients in whom OAC is scheduled to be discontinued during the follow-up period.
  3. Patients with a past history of ST.
  4. Patients with a planned coronary revascularization.
  5. Patients with a planned cardiovascular or non-cardiovascular surgery.
  6. Patients with expectation of survival less than one year.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01962545

Contacts
Contact: Takeshi Kimura, M.D. +81-75-751-4254 taketaka@kuhp.kyoto-u.ac.jp
Contact: Satoshi Shizuta, M.D. +81-75-751-3198 shizuta@kuhp.kyoto-u.ac.jp

Locations
Japan
Kyoto University Graduate School of Medicine Recruiting
Kyoto, Japan, 606-8507
Contact: Takeshi Kimura, M.D.    +81-75-751-4254    taketaka@kuhp.kyoto-u.ac.jp   
Contact: Satoshi Shizuta, M.D.    +81-75-751-3198    shizuta@kuhp.kyoto-u.ac.jp   
Principal Investigator: Takeshi Kimura, M.D.         
Sponsors and Collaborators
Satoshi Shizuta
Research Institute for Production Development
Daiichi Sankyo Co., Ltd.
Investigators
Principal Investigator: Takeshi Kimura, M.D. Kyoto University, Graduate School of Medicine
  More Information

No publications provided

Responsible Party: Satoshi Shizuta, Kyoto University, Kyoto University, Graduate School of Medicine
ClinicalTrials.gov Identifier: NCT01962545     History of Changes
Other Study ID Numbers: C740
Study First Received: October 5, 2013
Last Updated: May 31, 2015
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Kyoto University, Graduate School of Medicine:
Atrial Fibrillation
Percutaneous coronary intervention
Stent
Anticoagulant therapy
Antiplatelet therapy
Warfarin
NOAC
Aspirin
Clopidogrel

Additional relevant MeSH terms:
Atrial Fibrillation
Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Arrhythmias, Cardiac
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Vascular Diseases
Clopidogrel
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2015