Rivaroxaban Versus Warfarin in Acute Ischemic Stroke With Atrial Fibrillation (TripleAXEL)
|ClinicalTrials.gov Identifier: NCT02042534|
Recruitment Status : Completed
First Posted : January 23, 2014
Results First Posted : February 8, 2017
Last Update Posted : February 8, 2017
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 or disease||Intervention/treatment||Phase|
|Ischemic Stroke Transient Ischemic Attack||Drug: Rivaroxaban Drug: Warfarin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||195 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||January 2014|
|Actual Primary Completion Date :||December 2015|
|Actual Study Completion Date :||December 2015|
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.
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].
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.
- Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging [ Time Frame: 1 month after randomization ]
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
- The Number of Patients With Intracranial Bleeding [ Time Frame: at 1 month ]Intracranial bleeding confirmed by relevant neuroimagings
- The Number of Patients With Recurrent Ischemic Lesion [ Time Frame: at 1 month ]Recurrent ischemic lesion confirmed by relevant neuroimagings
- Length of Hospitalization [ Time Frame: at 1month ]Time to event will be calculated
- Number of Participants With Modified Rankin Score of 0 or 1 at Week 4 [ Time Frame: at 1 month ]
modified Rankin Score
0 : No symptoms at all
- : No significant disability despite symptoms; able to carry out all usual duties and activities
- : Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
- : Moderate disability; requiring some help, but able to walk without assistance
- : Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
- : Severe disability; bedridden, incontinent and requiring constant nursing care and attention
- : Dead
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02042534
|Korea, Republic of|
|Asan Medical Center|
|Seoul, Korea, Republic of, 138-736|
|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|