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

14 december 2016 uppdaterad av: Sun U. Kwon, Asan Medical Center

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.

Studieöversikt

Detaljerad beskrivning

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

Studietyp

Interventionell

Inskrivning (Faktisk)

195

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

19 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.

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.

Andra namn:
  • Xarelto
Aktiv komparator: 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.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging
Tidsram: 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

1 month after randomization

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
The Number of Patients With Intracranial Bleeding
Tidsram: at 1 month
Intracranial bleeding confirmed by relevant neuroimagings
at 1 month
The Number of Patients With Recurrent Ischemic Lesion
Tidsram: at 1 month
Recurrent ischemic lesion confirmed by relevant neuroimagings
at 1 month
Length of Hospitalization
Tidsram: at 1month
Time to event will be calculated
at 1month
Number of Participants With Modified Rankin Score of 0 or 1 at Week 4
Tidsram: at 1 month

modified Rankin Score

0 : No symptoms at all

  1. : No significant disability despite symptoms; able to carry out all usual duties and activities
  2. : Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
  3. : Moderate disability; requiring some help, but able to walk without assistance
  4. : Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
  5. : Severe disability; bedridden, incontinent and requiring constant nursing care and attention
  6. : Dead
at 1 month

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Samarbetspartners

Utredare

  • Huvudutredare: Sun Uck Kwon, PhD., Asan Medical Center
  • Huvudutredare: Keun-Sik Hong, PhD, InjeUniversityIlsanPaikHospital
  • Huvudutredare: Young Jae Kim, PhD, EWHA Womans University Mokdong Hospital
  • Huvudutredare: Yang Ha Hwang, PhD, Kyungpook National University Hospital
  • Huvudutredare: Jaekwan Cha, PhD, Dong-A University Hospital
  • Huvudutredare: Woo-Keun Seo, PhD, Korea University Guro Hospital
  • Huvudutredare: Eung-Gyu Kim, PhD, InjeUniversityBusanPaikHospital
  • Huvudutredare: Byung-Woo Yoon, PhD, Seoul National University Hospital
  • Huvudutredare: Kyung-Ho Yu, PhD, Hallym University Medical Center

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 januari 2014

Primärt slutförande (Faktisk)

1 december 2015

Avslutad studie (Faktisk)

1 december 2015

Studieregistreringsdatum

Först inskickad

17 januari 2014

Först inskickad som uppfyllde QC-kriterierna

20 januari 2014

Första postat (Uppskatta)

23 januari 2014

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

8 februari 2017

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

14 december 2016

Senast verifierad

1 december 2016

Mer information

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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