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- Ensaio Clínico 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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Seoul, Republica da Coréia, 138-736
- Asan Medical Center
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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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.
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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.
Outros nomes:
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Comparador Ativo: 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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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The Number of Patients With Intracranial Bleeding
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Sun Uck Kwon, PhD., Asan Medical Center
- Investigador principal: Keun-Sik Hong, PhD, InjeUniversityIlsanPaikHospital
- Investigador principal: Young Jae Kim, PhD, Ewha Womans University Mokdong Hospital
- Investigador principal: Yang Ha Hwang, PhD, Kyungpook National University Hospital
- Investigador principal: Jaekwan Cha, PhD, Dong-A University Hospital
- Investigador principal: Woo-Keun Seo, PhD, Korea University Guro Hospital
- Investigador principal: Eung-Gyu Kim, PhD, InjeUniversityBusanPaikHospital
- Investigador principal: Byung-Woo Yoon, PhD, Seoul National University Hospital
- Investigador principal: Kyung-Ho Yu, PhD, Hallym University Medical Center
Publicações e links úteis
Publicações Gerais
- 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.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Processos Patológicos
- Necrose
- Doenças cardíacas
- Doenças cardiovasculares
- Doenças Vasculares
- Distúrbios Cerebrovasculares
- Doenças Cerebrais
- Doenças do Sistema Nervoso Central
- Doenças do Sistema Nervoso
- Arritmias Cardíacas
- Isquemia Cerebral
- Infarte
- Infarto Cerebral
- Derrame
- AVC Isquêmico
- Isquemia
- Ataque Isquêmico Transitório
- Fibrilação atrial
- Infarto cerebral
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Inibidores de Protease
- Inibidores do Fator Xa
- Antitrombinas
- Inibidores de Serina Proteinase
- Anticoagulantes
- Rivaroxabana
- Varfarina
Outros números de identificação do estudo
- LMI-2013-1013
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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