Trial record 7 of 87 for:    Open Studies | "Warfarin"

Rivaroxaban Versus Warfarin in Acute Ischemic Stroke With Atrial Fibrillation (TripleAXEL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Asan Medical Center
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Sun U. Kwon, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT02042534
First received: January 17, 2014
Last updated: May 8, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Ischemic Stroke
Transient Ischemic Attack
Drug: Rivaroxaban
Drug: Warfarin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Composite of MRI-defined intracranial bleeding and recurrent ischemic lesion [ Time Frame: 1 month after randomization ] [ Designated as safety issue: Yes ]

    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



Secondary Outcome Measures:
  • The number of patients with Intracranial bleeding [ Time Frame: at 1 month ] [ Designated as safety issue: Yes ]
    Intracranial bleeding confirmed by relevant neuroimagings

  • The number of patients with recurrent ischemic lesion [ Time Frame: at 1 month ] [ Designated as safety issue: No ]
    Recurrent ischemic lesion confirmed by relevant neuroimagings

  • Length of hospitalization [ Time Frame: at 1month ] [ Designated as safety issue: No ]
    Time to event will be calculated

  • modified Rankin Score [ Time Frame: at 1 month ] [ Designated as safety issue: No ]

Estimated Enrollment: 196
Study Start Date: January 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivaroxaban
Rivaroxaban 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.
Drug: Rivaroxaban

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.

Other Name: Xarelto
Active Comparator: Warfarin
Patients 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].
Drug: Warfarin
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.
Other Name: Warfarin

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: All of below

  • 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

Exclusion Criteria: Any of below

  • 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
  • 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
  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: NCT02042534

Contacts
Contact: YunJeong In, BA +82-2-3010-8691 yjin@amc.seoul.kr
Contact: SulHwa Kim, BA +82-2-3010-7365 irbksh@amc.seoul.kr

Locations
Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
Contact: YunJeong In, BA    +82-2-3010-8691    yjin@amc.seoul.kr   
Contact: SulHwa Kim, BA    +82-2-3010-7365    irbksh@amc.seoul.kr   
Principal Investigator: Sun Uck Kwon, PhD.         
Sponsors and Collaborators
Asan Medical Center
Bayer
Investigators
Principal Investigator: Sun Uck Kwon, PhD. Asan Medical Center
Principal Investigator: Keun-Sik Hong, PhD InjeUniversityIlsanPaikHospital
Principal Investigator: Young Jae Kim, PhD Ewha Womans University Mokdong Hospital
Principal Investigator: Yang Ha Hwang, PhD Kyungpook National University
Principal Investigator: Jaekwan Cha, PhD Dong-A University Hospital
Principal Investigator: Woo-Keun Seo, PhD Korea University Guro Hospital
Principal Investigator: Eung-Gyu Kim, PhD InjeUniversityBusanPaikHospital
Principal Investigator: Byung-Woo Yoon, PhD Seoul National University Hospital
Principal Investigator: Kyung-Ho Yu, PhD Hallym University Medical Center
  More Information

No publications provided

Responsible Party: Sun U. Kwon, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT02042534     History of Changes
Other Study ID Numbers: LMI-2013-1013
Study First Received: January 17, 2014
Last Updated: May 8, 2014
Health Authority: Korea: Ministry of Food and Drug Safety

Keywords provided by Asan Medical Center:
stroke
TIA

Additional relevant MeSH terms:
Warfarin
Atrial Fibrillation
Ischemic Attack, Transient
Ischemia
Stroke
Cerebral Infarction
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Brain Infarction
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014