Rivaroxaban Versus Warfarin in Acute Ischemic Stroke With Atrial Fibrillation (TripleAXEL)
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.
Transient Ischemic Attack
|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|
- 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
- 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 ]
|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)|
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.
Other Name: Warfarin
Primary endpoint: Composite of MRI-defined intracranial bleeding and recurrent ischemic lesion within 1 month after randomization (rivaroxaban vs conventional warfarin)
Please refer to this study by its ClinicalTrials.gov identifier: NCT02042534
|Contact: YunJeong In, BAfirstname.lastname@example.org|
|Contact: SulHwa Kim, BAemail@example.com|
|Korea, Republic of|
|Asan Medical Center||Recruiting|
|Seoul, Korea, Republic of, 138-736|
|Contact: YunJeong In, BA +82-2-3010-8691 firstname.lastname@example.org|
|Contact: SulHwa Kim, BA +82-2-3010-7365 email@example.com|
|Principal Investigator: Sun Uck Kwon, PhD.|
|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|