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Ischemic StrokePhase 2TripleAXELNCT02042534

Rivaroxaban Versus Warfarin in Acute Ischemic Stroke With Atrial Fibrillation

A Phase 2 study testing Rivaroxaban and Warfarin in people with Ischemic Stroke and Transient Ischemic Attack, run by Asan Medical Center at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Rationale Acute ischemic stroke due to atrial fibrillation (AF) carries a high risk for early recurrence. In acute stage, guidelines recommend aspirin, but do not recommend anticoagulation due to the increased risk of intracranial bleeding. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Ischemic Stroke, Transient Ischemic Attack
What is being tested?
Rivaroxaban and Warfarin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
195 participants
Where
1 siteSouth Korea
Study dates
Jan 2014to Dec 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Who may be able to join

  • Acute ischemic stroke or TIA presumed to be cardioembolic origin (within 5 days from stroke onset) with mild severity: infarct size on DWI less than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere
  • Atrial fibrillation including paroxysmal atrial fibrillation: atrial fibrillation must be documented by ECG evidence (e.g., 12-lead ECG, rhythm strip, Holter, pacemaker interrogation) within 30 days before randomization. This could be obtained from a notation in the subject's record (e.g., medical chart, hospital discharge summary).
  • Age ≥19 years
  • Informed consent

Who cannot join

  • Chronic renal failure (GFR less than 30ml/min) or severe hepatic impairment
  • Significant hemorrhagic transformation (parenchymal hematoma type I or II by the ECASS definition)
  • Stroke mechanism of presumed small vessel occlusion: single small subcortical infarct in the perforating artery territory
  • Large hemispheric or cerebellar infarction; larger than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere
  • Mechanical valve requiring warfarin therapy
  • Active internal bleeding
Show all 17Show fewer
  • Prior history of symptomatic intracranial bleeding
  • : patients with asymptomatic bleedings or microbleedings on MRI are eligible for inclusion
  • Major surgery or major trauma within 30 days that might be associated with increased bleeding risk
  • Clinically significant gastrointestinal bleeding within 6 months
  • Intravenous tissue plasminogen activator use or mechanical embolectomy within 48 hours plus 'significant hemorrhagic transformation as described above (exclusion criteria 2)' or 'large hemispheric infarction or cerebellar infarction as described above (exclusion criteria 4)'
  • : patients achieving successful reperfusion without hemorrhage nor large infarction are eligible for enrollment
  • Severe anemia: hemoglobin <10 g/dL
  • Bleeding diathesis; thrombocytopenia (<90,000/µL, prolonged PT (INR>1.7)
  • Sustained uncontrolled hypertension: SBP >180 mmHg or DBP >100 mmHg
  • Severe devastating illness, such terminal cancer, hepatic failure; therefore, the participants have a life expectancy less than 6 months.
  • Planned invasive procedure with potential for uncontrolled bleeding, including major surgery

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Asan Medical Center

    Seoul, 138-736

Other trials in South Korea

About this study

Official title: Rivaroxaban Versus Warfarin in Acute Ischemic Stroke With Atrial Fibrillation: Acute Stroke With Xarelto to Reduce Intracranial Bleeding, Recurrent Embolic Stroke, and Hospital Stay, Phase 2, Conceptual Multicenter Trial

Rationale Acute ischemic stroke due to atrial fibrillation (AF) carries a high risk for early recurrence. In acute stage, guidelines recommend aspirin, but do not recommend anticoagulation due to the increased risk of intracranial bleeding. Since, aspirin has a limited efficacy of preventing recurrent stroke in AF, expert consensus suggests early anticoagulation in non-severe stroke with AF. The current practice for acute ischemic stroke patients with AF is delayed warfarin administration with aspirin use for non-minor stroke or immediate warfarin administration (sometimes with heparin bridging) for minor stroke. However, conventional anticoagulation with warfarin in acute ischemic stroke with AF has the following limitations: 1) risk of intracranial bleeding particularly in acute stage, 2) delayed action and transient paradoxical thrombogenic tendency due to the inhibition of protein C, resulting in the risk of early recurrent embolic stroke, and 3) prolongation of hospitalization waiting for full anticoagulation. In contrast, as compared to warfarin, rivaroxaban is advantageous for reduced risk of intracranial bleeding and immediate anticoagulation efficacy.

Goal The current trial will examine whether early initiation (within 5 days from stroke onset) of rivaroxaban as compared to conventional warfarin would reduce intracranial bleeding, recurrent embolic stroke, and hospital stay in patients with acute ischemic stroke due to AF.

Read the detailed description

Primary endpoint: Composite of MRI-defined intracranial bleeding and recurrent ischemic lesion within 1 month after randomization (rivaroxaban vs conventional warfarin)

Being tested
Rivaroxaban, Warfarin
Keywords
stroke, TIA
Medical subject headings
Ischemic Stroke, Ischemic Attack, Transient, Stroke

What participants receive

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

  • RivaroxabanDrug

    Also called Xarelto

    Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min.

    The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.

  • WarfarinDrug

    To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.

Study groups in NCT02042534
Study groupRoleWhat they receive
RivaroxabanExperimentalRivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days.
Receives: Drug: Rivaroxaban
WarfarinActive comparatorPatients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 [2.0 - 3.0].
Receives: Drug: Warfarin

What is being measured

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

  1. Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging

    Intracranial bleeding: symptomatic hemorrhage confirmed by CT or MRI or asymptomatic hemorrhage on follow-up GRE or SWI imaging at 1 month

    Recurrent ischemic lesion: symptomatic ischemic stroke confirmed by relevant neuroimagings or asymptomatic recurrent ischemic lesion on follow-up or FLAIR imaging at 1 month

    Measured: 1 month after randomization

Secondary outcomes (4)

  1. The Number of Patients With Intracranial Bleeding

    Intracranial bleeding confirmed by relevant neuroimagings

    Measured: at 1 month

  2. The Number of Patients With Recurrent Ischemic Lesion

    Recurrent ischemic lesion confirmed by relevant neuroimagings

    Measured: at 1 month

  3. Length of Hospitalization

    Time to event will be calculated

    Measured: at 1month

  4. Number of Participants With Modified Rankin Score of 0 or 1 at Week 4

    modified Rankin Score

    0 : No symptoms at all

    1. : No significant disability despite symptoms; able to carry out all usual duties and activities
    2. : Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
    3. : Moderate disability; requiring some help, but able to walk without assistance
    4. : Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
    5. : Severe disability; bedridden, incontinent and requiring constant nursing care and attention
    6. : Dead

    Measured: at 1 month

Timeline

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

  1. First posted23 Jan 2014 (estimated)
  2. Study startJan 2014
  3. Primary completionDec 2015
  4. Study completionDec 2015

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
195 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02042534
Sponsor's protocol ID
LMI-2013-1013
Acronym
TripleAXEL
Status last verified
Dec 2016
First submitted
17 Jan 2014
Last updated
8 Feb 2017
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Hong KS, Kwon SU, Lee SH, Lee JS, Kim YJ, Song TJ, Kim YD, Park MS, Kim EG, Cha JK, Sung SM, Yoon BW, Bang OY, Seo WK, Hwang YH, Ahn SH, Kang DW, Kang HG, Yu KH; Phase 2 Exploratory Clinical Study to Assess the Effects of Xarelto (Rivaroxaban) Versus Warfarin on Ischemia, Bleeding, and Hospital Stay in Acute Cerebral Infarction Patients With Non-valvular Atrial Fibrillation (Triple AXEL) Study Group. Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation-Related Mild Ischemic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2017 Oct 1;74(10):1206-1215. doi: 10.1001/jamaneurol.2017.2161.

    PubMed 28892526

  • Hong KS, Choi YJ, Kwon SU; Triple AXEL Investigators. Rationale and design of Triple AXEL: trial for early anticoagulation in acute ischemic stroke patients with nonvalvular atrial fibrillation. Int J Stroke. 2015 Jan;10(1):128-33. doi: 10.1111/ijs.12386. Epub 2014 Oct 26.

    PubMed 25346499

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rivaroxaban and Warfarin in people with Ischemic Stroke and Transient Ischemic Attack, run by Asan Medical Center at 1 site in South Korea.

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 4 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: finished, as of the sponsor's last update on 8 Feb 2017. 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 South Korea. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging (time frame: 1 month 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 NCT02042534, 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 8 Feb 2017.

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