- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT02042534
Rivaroxaban Versus Warfarin in Acute Ischemic Stroke With Atrial Fibrillation (TripleAXEL)
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.
연구 개요
상세 설명
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
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Seoul, 대한민국, 138-736
- Asan Medical Center
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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.
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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.
다른 이름들:
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활성 비교기: 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].
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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.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging
기간: 1 month after randomization
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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 |
1 month after randomization
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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The Number of Patients With Intracranial Bleeding
기간: at 1 month
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Intracranial bleeding confirmed by relevant neuroimagings
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at 1 month
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The Number of Patients With Recurrent Ischemic Lesion
기간: at 1 month
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Recurrent ischemic lesion confirmed by relevant neuroimagings
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at 1 month
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Length of Hospitalization
기간: at 1month
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Time to event will be calculated
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at 1month
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Number of Participants With Modified Rankin Score of 0 or 1 at Week 4
기간: at 1 month
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modified Rankin Score 0 : No symptoms at all
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at 1 month
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공동 작업자 및 조사자
협력자
수사관
- 수석 연구원: Sun Uck Kwon, PhD., Asan Medical Center
- 수석 연구원: Keun-Sik Hong, PhD, InjeUniversityIlsanPaikHospital
- 수석 연구원: Young Jae Kim, PhD, Ewha Womans University Mokdong Hospital
- 수석 연구원: Yang Ha Hwang, PhD, Kyungpook National University Hospital
- 수석 연구원: Jaekwan Cha, PhD, Dong-A University Hospital
- 수석 연구원: Woo-Keun Seo, PhD, Korea University Guro Hospital
- 수석 연구원: Eung-Gyu Kim, PhD, InjeUniversityBusanPaikHospital
- 수석 연구원: Byung-Woo Yoon, PhD, Seoul National University Hospital
- 수석 연구원: Kyung-Ho Yu, PhD, Hallym University Medical Center
간행물 및 유용한 링크
일반 간행물
- 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.
- 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. Erratum In: Int J Stroke. 2016 Jul;11(5):NP63.
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- LMI-2013-1013
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
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