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Optimal Antithrombotic Therapy in Ischemic Stroke Patients With Non-Valvular Atrial Fibrillation and Atherothrombosis (ATIS-NVAF)

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ClinicalTrials.gov Identifier: NCT03062319
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : December 27, 2017
Sponsor:
Collaborators:
Network for Clinical Stroke Trials
The BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program
Information provided by (Responsible Party):
Hiroshi Yamagami, National Cerebral and Cardiovascular Center

Brief Summary:
The Purpose of this open-label randomized controlled multicenter trial is to evaluate the efficacy and safety of mono-drug therapy with oral anticoagulant compared to combination therapy with antiplatelet drug, in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis.

Condition or disease Intervention/treatment Phase
Ischemic Stroke Atrial Fibrillation Atherothrombosis Drug: Oral Anticoagulant Drug: Antiplatelet Drug Phase 4

Detailed Description:
The Purpose of this open-label randomized controlled multicenter trial is to evaluate the efficacy and safety of mono-drug therapy with oral anticoagulant compared to combination therapy with antiplatelet drug, in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis. Target sample size is 400. The primary outcome is a composite endpoint of ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization) and major bleeding defined by the International Society on Thrombosis and Haemostasis(ISTH) criteria within 2 years after randomization.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Optimal Antithrombotic Therapy in Ischemic Stroke Patients With Non-Valvular Atrial Fibrillation and Atherothrombosis
Actual Study Start Date : April 6, 2017
Estimated Primary Completion Date : January 31, 2021
Estimated Study Completion Date : January 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Dual-therapy group
Dual-therapy group: single anticoagulant drug and single antiplatelet drug. The dosage is determined according to each drug's package insert in Japan. In patients treated with warfarin, 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 is recommended according to the Japanese guidelines.
Drug: Oral Anticoagulant
warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban

Drug: Antiplatelet Drug
aspirin, clopidogrel, prasugrel, ticlopidine, or cilostazol

Active Comparator: Single-therapy group
Single-therapy group: single anticoagulant drug. The dosage is determined according to each drug's package insert in Japan. In patients treated with warfarin, 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 is recommended according to the Japanese guidelines.
Drug: Oral Anticoagulant
warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban




Primary Outcome Measures :
  1. Composite endpoint of ischemic cardiovascular events and major bleeding [ Time Frame: 2 years after randomization ]
    One of the following ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, or ischemic events requiring urgent revascularization), or major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria


Secondary Outcome Measures :
  1. All-cause mortality [ Time Frame: 2 years after randomization ]
    All-cause mortality

  2. Ischemic cardiovascular events [ Time Frame: 2 years after randomization ]
    Ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization)

  3. All ischemic cardiovascular events including transient ischemia [ Time Frame: 2 years after randomization ]
    All ischemic cardiovascular events including transient ischemia (cardiovascular death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction, unstable angina pectoris, systemic embolism, progression of symptomatic peripheral artery disease, ischemic events requiring urgent revascularization)

  4. Ischemic stroke [ Time Frame: 2 years after randomization ]
    Ischemic stroke

  5. Myocardial infarction and cardiovascular death [ Time Frame: 2 years after randomization ]
    Myocardial infarction and cardiovascular death

  6. major bleeding [ Time Frame: 2 years after randomization ]
    major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria

  7. Intracranial hemorrhage [ Time Frame: 2 years after randomization ]
    Intracranial hemorrhage



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Ages Eligible for Study:   20 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with an acute ischemic stroke or TIA from 8 days and up to 360 days from the onset of symptoms
  2. Age: 20-90 years.
  3. Patients with non-valvular atrial fibrillation (chronic or paroxysmal) who start or continue taking an oral anticoagulant
  4. Patients who have one of the following atherothrombotic diseases

    1. A past history of ischemic heart disease (myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI)
    2. A past history of peripheral artery disease (symptomatic peripheral arterial occlusive disease, lower extremity bypass surgery/angioplasty/stenting)
    3. Carotid artery stenosis (symptomatic or asymptomatic (=>50% diameter), a history of carotid artery stenting (CAS) or carotid endarterectomy (CEA))
    4. Intracranial artery stenosis (=>50% stenosis of the diameter of a major intracranial artery: intracranial internal carotid artery, anterior cerebral artery (ACA)-A1 and A2, middle cerebral artery (MCA)-M1 and M2, posterior cerebral artery (PCA)-P1 and P2, vertebral artery, and basilar artery; a history of intracranial stent placement or intracranial bypass surgery)
    5. A past history of atherothrombotic brain infarction, lacunar infarction, or branch atheromatous disease
  5. Patients who can walk independently (modified Rankin Scale score =<3)
  6. Patients who can take oral medications
  7. Patients who can receive follow-up survey
  8. Provision of written informed consent either directly or by a suitable surrogate

Exclusion Criteria:

  1. History of myocardial infarction or acute coronary syndrome within the past 12 months
  2. Patients who underwent PCI with drug-eluting stents within the past 12 months or PCI with bare-metal stents within the past 3 months
  3. Patients who underwent carotid artery stent placement, intracranial stent placement, or lower extremity stent placement within the past 3 months
  4. History of symptomatic intracranial hemorrhage or gastrointestinal bleeding within the past 6 months
  5. Hemorrhagic diathesis or blood coagulation disorders
  6. Platelet counts <100,000 /mm3 at enrollment.
  7. Severe anemia (hemoglobin <7 g/dL)
  8. Severe renal failure (creatinine clearance =<15 mL/min) or undergoing chronic hemodialysis.
  9. Severe liver dysfunction (Grade B or C of the Child-Pugh classification)
  10. Patients who are unable to walk independently (modified Rankin Scale score =>4)
  11. Pregnant or possibly pregnant women
  12. Active cancer
  13. Expectation of survival less than 2 years
  14. Anticoagulant or antiplatelet is scheduled to be discontinued for more than 4 weeks during the follow-up period
  15. Planned revascularization procedure during the follow-up period
  16. Patients who are enrolled in other trials
  17. 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): NCT03062319


Contacts
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Contact: Hiroshi Yamagami, MD +81-6-6833-5012 ext 8025 yamagami-brain@umin.ac.jp
Contact: Shuhei Okazaki, MD +81-6-6833-5012 ext 8123 s-okazaki@umin.ac.jp

Locations
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Japan
Kobe City Medical Center General Hospital Recruiting
Kobe, Hyogo, Japan, 650-0047
Contact: Nobuyuki Sakai, MD    078-302-7537    n.sakai@siren.ocn.ne.jp   
Contact: Nobuyuki Ohara, MD    078-302-7537    nobuyuki.ohara@gmail.com   
National Cerebral and Cardiovascular Center Recruiting
Suita, Osaka, Japan, 565-8565
Contact: Hiroshi Yamagami, MD    06-6833-5012 ext 8025    yamagami-brain@umin.ac.jp   
Contact: Shuhei Okazaki, MD    06-6833-5012 ext 8123    s-okazaki@umin.ac.jp   
Sponsors and Collaborators
National Cerebral and Cardiovascular Center
Network for Clinical Stroke Trials
The BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program
Investigators
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Principal Investigator: Hiroshi Yamagami, MD National Cerebral and Cardiovascular Center

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Responsible Party: Hiroshi Yamagami, Head Physician, Division of Stroke Care Unit, National Cerebral and Cardiovascular Center
ClinicalTrials.gov Identifier: NCT03062319     History of Changes
Other Study ID Numbers: ATIS-NVAF
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: December 27, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hiroshi Yamagami, National Cerebral and Cardiovascular Center:
anticoagulant
antiplatelet

Additional relevant MeSH terms:
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Platelet Aggregation Inhibitors
Stroke
Atrial Fibrillation
Ischemia
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Arrhythmias, Cardiac
Heart Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Warfarin
Anticoagulants