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AzTrials

Ischemic StrokePhase 4ATIS-NVAFNCT03062319

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

A Phase 4 study testing Oral Anticoagulant and Antiplatelet Drug in people with Ischemic Stroke and Atrial Fibrillation, run by National Hospital Organization Osaka National Hospital at 1 site in Japan.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
Oral Anticoagulant and Antiplatelet Drug
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
321 participants
Where
1 siteJapan
Study dates
6 Apr 2017to 18 Jul 2023
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

1 site in 1 country.

Japan1 site

  • National Hospital Organization Osaka National Hospital

    Osaka, Osaka, 540-0006

Other trials in Japan

About this study

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.

Read the 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.

Being tested
Oral Anticoagulant, Antiplatelet Drug
Keywords
anticoagulant, antiplatelet
Medical subject headings
Ischemic Stroke, Atrial Fibrillation, Thrombosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral AnticoagulantDrug

    warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban

  • Antiplatelet DrugDrug

    aspirin, clopidogrel, prasugrel, ticlopidine, or cilostazol

Study groups in NCT03062319
Study groupRoleWhat they receive
Dual-therapy groupActive comparatorDual-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.
Receives: Drug: Oral Anticoagulant; Drug: Antiplatelet Drug
Single-therapy groupActive comparatorSingle-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.
Receives: Drug: Oral Anticoagulant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 2 years after randomization

Secondary outcomes (7)

  1. All-cause mortality

    All-cause mortality

    Measured: 2 years after randomization

  2. Ischemic cardiovascular events

    Ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization)

    Measured: 2 years after randomization

  3. 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)

    Measured: 2 years after randomization

  4. Ischemic stroke

    Ischemic stroke

    Measured: 2 years after randomization

  5. Myocardial infarction and cardiovascular death

    Myocardial infarction and cardiovascular death

    Measured: 2 years after randomization

  6. major bleeding

    major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria

    Measured: 2 years after randomization

  7. Intracranial hemorrhage

    Intracranial hemorrhage

    Measured: 2 years after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2017
  2. Study start6 Apr 2017
  3. Primary completion18 Jul 2023
  4. Study completion18 Jul 2023

Why it stopped: The trial was terminated at the planned interim analysis for futility on July 18, 2023.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
321 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03062319
Sponsor's protocol ID
ATIS-NVAF
Acronym
ATIS-NVAF
Status last verified
Dec 2024
First submitted
8 Feb 2017
Last updated
27 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Okazaki S, Tanaka K, Yazawa Y, Doijiri R, Koga M, Ihara M, Yamamoto S, Kamiyama K, Honda Y, Uchida K, Yoshimoto T, Asakura K, Omae K, Tanaka K, Maeda H, Yamamoto H, Hirano T, Toyoda K, Iguchi Y, Noguchi T, Okada Y, Kitagawa K, Sakai N, Yamagami H; ATIS-NVAF Trial Investigators. Optimal Antithrombotics for Ischemic Stroke and Concurrent Atrial Fibrillation and Atherosclerosis: A Randomized Clinical Trial. JAMA Neurol. 2025 Dec 1;82(12):1227-1234. doi: 10.1001/jamaneurol.2025.3662.

    PubMed 41051787

  • Okazaki S, Yamamoto H, Asakura K, Omae K, Maeda H, Tanaka K, Yamamoto S, Hirano T, Iguchi Y, Sakaguchi M, Koga M, Ihara M, Toyoda K, Noguchi T, Sakai N, Yamagami H. Optimal antithrombotic therapy in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis: study protocol for a randomized controlled trial. Front Neurol. 2024 Oct 23;15:1468523. doi: 10.3389/fneur.2024.1468523. eCollection 2024.

    PubMed 39539664

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Oral Anticoagulant and Antiplatelet Drug in people with Ischemic Stroke and Atrial Fibrillation, run by National Hospital Organization Osaka National Hospital at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The trial was terminated at the planned interim analysis for futility on July 18, 2023.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite endpoint of ischemic cardiovascular events and major bleeding (time frame: 2 years after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03062319, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2024.

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