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

Primary Purpose

Ischemic Stroke, Atrial Fibrillation, Atherothrombosis

Status
Recruiting
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
Oral Anticoagulant
Antiplatelet Drug
Sponsored by
National Hospital Organization Osaka National Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Ischemic Stroke focused on measuring anticoagulant, antiplatelet

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 or older
  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 without severe disability (modified Rankin Scale score =<4)
  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 with severe disability requires constant nursing care, bedridden (modified Rankin Scale score =5)
  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

Sites / Locations

  • Kobe City Medical Center General HospitalRecruiting
  • National Hospital Organization Osaka National HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Dual-therapy group

Single-therapy group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Composite endpoint of ischemic cardiovascular events and major bleeding
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

All-cause mortality
All-cause mortality
Ischemic cardiovascular events
Ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization)
All ischemic cardiovascular events including transient ischemia
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)
Ischemic stroke
Ischemic stroke
Myocardial infarction and cardiovascular death
Myocardial infarction and cardiovascular death
major bleeding
major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria
Intracranial hemorrhage
Intracranial hemorrhage

Full Information

First Posted
February 8, 2017
Last Updated
October 8, 2020
Sponsor
National Hospital Organization Osaka National Hospital
Collaborators
Network for Clinical Stroke Trials, The BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program
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1. Study Identification

Unique Protocol Identification Number
NCT03062319
Brief Title
Optimal Antithrombotic Therapy in Ischemic Stroke Patients With Non-Valvular Atrial Fibrillation and Atherothrombosis
Acronym
ATIS-NVAF
Official Title
Optimal Antithrombotic Therapy in Ischemic Stroke Patients With Non-Valvular Atrial Fibrillation and Atherothrombosis
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Recruiting
Study Start Date
April 6, 2017 (Actual)
Primary Completion Date
April 30, 2022 (Anticipated)
Study Completion Date
April 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Hospital Organization Osaka National Hospital
Collaborators
Network for Clinical Stroke Trials, The BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke, Atrial Fibrillation, Atherothrombosis
Keywords
anticoagulant, antiplatelet

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dual-therapy group
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Single-therapy group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Oral Anticoagulant
Intervention Description
warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban
Intervention Type
Drug
Intervention Name(s)
Antiplatelet Drug
Intervention Description
aspirin, clopidogrel, prasugrel, ticlopidine, or cilostazol
Primary Outcome Measure Information:
Title
Composite endpoint of ischemic cardiovascular events and major bleeding
Description
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
Time Frame
2 years after randomization
Secondary Outcome Measure Information:
Title
All-cause mortality
Description
All-cause mortality
Time Frame
2 years after randomization
Title
Ischemic cardiovascular events
Description
Ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization)
Time Frame
2 years after randomization
Title
All ischemic cardiovascular events including transient ischemia
Description
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)
Time Frame
2 years after randomization
Title
Ischemic stroke
Description
Ischemic stroke
Time Frame
2 years after randomization
Title
Myocardial infarction and cardiovascular death
Description
Myocardial infarction and cardiovascular death
Time Frame
2 years after randomization
Title
major bleeding
Description
major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria
Time Frame
2 years after randomization
Title
Intracranial hemorrhage
Description
Intracranial hemorrhage
Time Frame
2 years after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with an acute ischemic stroke or TIA from 8 days and up to 360 days from the onset of symptoms Age 20 or older Patients with non-valvular atrial fibrillation (chronic or paroxysmal) who start or continue taking an oral anticoagulant Patients who have one of the following atherothrombotic diseases A past history of ischemic heart disease (myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) A past history of peripheral artery disease (symptomatic peripheral arterial occlusive disease, lower extremity bypass surgery/angioplasty/stenting) Carotid artery stenosis (symptomatic or asymptomatic (=>50% diameter), a history of carotid artery stenting (CAS) or carotid endarterectomy (CEA)) 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) A past history of atherothrombotic brain infarction, lacunar infarction, or branch atheromatous disease Patients without severe disability (modified Rankin Scale score =<4) Patients who can take oral medications Patients who can receive follow-up survey Provision of written informed consent either directly or by a suitable surrogate Exclusion Criteria: History of myocardial infarction or acute coronary syndrome within the past 12 months Patients who underwent PCI with drug-eluting stents within the past 12 months or PCI with bare-metal stents within the past 3 months Patients who underwent carotid artery stent placement, intracranial stent placement, or lower extremity stent placement within the past 3 months History of symptomatic intracranial hemorrhage or gastrointestinal bleeding within the past 6 months Hemorrhagic diathesis or blood coagulation disorders Platelet counts <100,000 /mm3 at enrollment. Severe anemia (hemoglobin <7 g/dL) Severe renal failure (creatinine clearance =<15 mL/min) or undergoing chronic hemodialysis. Severe liver dysfunction (Grade B or C of the Child-Pugh classification) Patients with severe disability requires constant nursing care, bedridden (modified Rankin Scale score =5) Pregnant or possibly pregnant women Active cancer Expectation of survival less than 2 years Anticoagulant or antiplatelet is scheduled to be discontinued for more than 4 weeks during the follow-up period Planned revascularization procedure during the follow-up period Patients who are enrolled in other trials Patients judged as inappropriate for this study by investigators
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hiroshi Yamagami, MD
Phone
+81-6-6942-1331
Email
yamagami-brain@umin.ac.jp
First Name & Middle Initial & Last Name or Official Title & Degree
Shuhei Okazaki, MD
Phone
+81-6-6879-3576
Email
s-okazaki@umin.ac.jp
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hiroshi Yamagami, MD
Organizational Affiliation
National Hospital Organization Osaka National Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kobe City Medical Center General Hospital
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
650-0047
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nobuyuki Sakai, MD
Phone
078-302-7537
Email
n.sakai@siren.ocn.ne.jp
First Name & Middle Initial & Last Name & Degree
Nobuyuki Ohara, MD
Phone
078-302-7537
Email
nobuyuki.ohara@gmail.com
Facility Name
National Hospital Organization Osaka National Hospital
City
Osaka
ZIP/Postal Code
540-0006
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hiroshi Yamagami, MD
Phone
+81-6-6942-1331
Email
yamagami-brain@umin.ac.jp
First Name & Middle Initial & Last Name & Degree
Shuhei Okazaki, MD
Phone
+81-6-6879-3576
Email
s-okazaki@umin.ac.jp

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Optimal Antithrombotic Therapy in Ischemic Stroke Patients With Non-Valvular Atrial Fibrillation and Atherothrombosis

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