To assess whether a rivaroxaban-based anticoagulation strategy, following successful TAVR, compared to an antiplatelet-based strategy, is superior in reducing death or first thromboembolic events (DTE).To assess the primary bleeding events (PBE) of…
ID
Source
Brief title
Condition
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy Endpoint: death or first adjudicated thromboembolic event
(DTE) defined as the composite of allcause death and adjudicated any stroke,
myocardial infarction (MI), symptomatic valve thrombosis, pulmonary embolism
(PE), deep vein thrombosis (DVT), or non-CNS systemic embolism.
Primary Safety Endpoint: primary bleeding event (PBE) defined as the composite
of adjudicated life-threatening, disabling or major bleeding, classified
according to the valve academic research consortium (VARC) definitions
following the bleeding academic research consortium (BARC) classification.
Secondary outcome
The composite of TIMI major or minor bleeds
ISTH major bleeding
The composite of BARC 2, 3, or 5 bleeding
Background summary
Calcific aortic valve stenosis is characterized by an increased thrombogenic
and inflammatory profile (2). Long-term oral antithrombotic treatment after
TAVR aims to prevent complications, notably ischemic stroke and MI as well as
thrombo-embolism related to deep vein thrombosis, pulmonary embolism, valve
thrombosis, or systemic embolism while minimizing bleeding risk. The baseline
risk for ischemic and thromboembolic complications is determined by
comorbidities such as concomitant coronary artery disease (CAD), which is
present in 20-70% of patients eligible for TAVR. Furthermore, in-hospital AF
may occur in about one-third of patients referred for TAVR (20). Therefore, the
actual standard of care after TAVR, i.e. DAPT, is not optimal in targeting the
underlying pathophysiological mechanisms in severe AS. Rivaroxaban, through the
inhibition
of the pathways underlying the increased thrombogenicity, may effectively
prevent Integrated Clinical Study Protocol No. 17938 28 SEP 2015 Version: 2.0
Page: 22 of 94 thrombotic complications after TAVR without exposing this
elderly (57) population to an increased bleeding risk.
Study objective
To assess whether a rivaroxaban-based anticoagulation strategy, following
successful TAVR, compared to an antiplatelet-based strategy, is superior in
reducing death or first thromboembolic events (DTE).
To assess the primary bleeding events (PBE) of the rivaroxaban-based strategy,
followingTAVR, compared to an antiplatelet-based strategy.
Study design
Event-driven, randomized, open-label with blinded endpoint
evaluation, parallel-group, active-controlled, multicenter
international study.
Intervention
Rivaroxaban-based strategy:
The first dose of rivaroxaban (10 mg once-daily) is given either immediately
after randomization or within 24-72 hours after the last intake of clopidogrel.
Rivaroxaban 10 mg once-daily can be taken with or without food. ASA 75-100 mg
once-daily is to be continued unchanged or started immediately after
randomization if not already being taken. ASA is discontinued after 90 days
from randomization. Rivaroxaban is continued until the efficacy cut-off date,
i.e. when the predefined number of efficacy endpoints is reached. In the event
of NOAF the dose of rivaroxaban is switched from 10 mg once-daily to 20 or 15
mg once-daily, depending on renal function. Rivaroxaban 20 and 15 mg once-daily
should be taken with food. Up to 90 days after randomization, ASA 75-100 mg
once-daily is to be continued unchanged. After 90 days from randomization, ASA
is discontinued and rivaroxaban 20 or 15 mg once-daily is continued alone until
the efficacy cut-off date.
Antiplatelet-based strategy:
Clopidogrel 75 mg once-daily and ASA 75-100 mg once-daily are to be continued
unchanged, or to be started at the time of randomization if not already being
taken. In subjects that are clopidogrel-naïve at randomization a single loading
dose of at least 300 mg clopidogrel should be administered followed by
clopidogrel 75 mg once-daily. Clopidogrel must be discontinued at 90 days
post-randomization and ASA 75-100 mg once-daily is to be continued until the
efficacy cut-off date.In the event of NOAF, the antiplatelet-based strategy
will be stopped and a VKA with a target INR 2-3 started. ASA 75-100mg
once-daily is to be continued in combination with VKA until 90 days after
randomization. After 90 days, ASA must be discontinued and VKA continued alone
until the efficacy cut-off date.
Study burden and risks
Medication risks:
thrombocythemia
liver disease
dizziness headache
muscle Haemorrhage
bleeding
medication allergy and shortness of breath
N/A N/A
Leverkusen 51368
DE
N/A N/A
Leverkusen 51368
DE
Listed location countries
Age
Inclusion criteria
Key inclusion criteria:
• Successful TAVR of a native aortic valve stenosis (either native of valve-in-valve)
• By iliofemoral or subclavian access
• With any approved/marketed device
• Written informed consent (IC)
Exclusion criteria
Key exclusion criteria:
• Atrial fibrillation (AF), current or previous, with an ongoing indication for oral anticoagulant treatment
• Any other indication for continued treatment with any oral anticoagulant (OAC)
• Known bleeding diathesis (such as but not limited to active internal bleeding, clinically significant bleeding, platelet count <= 50,000/mm3 at screening, hemoglobin level < 8.5 g/dL, active peptic ulcer or known gastrointestinal (GI) bleeding, history of intracranial hemorrhage or subdural hematoma)
• Any ongoing absolute indication for dual-antiplatelet therapy (DAPT) at time of screening that is unrelated to the TAVR procedure.
• Clinically overt stroke within the last 3 months
• Planned coronary or vascular intervention or major surgery
• Severe renal impairment (eGFR < 30 mL/min/1.73 m2) or on dialysis, or post-TAVR unresolved acute kidney injury with renal dysfunction stage 2 or higher
• Moderate and severe hepatic impairement (Child-Pugh Class B or C) or any hepatic disease associated with coagulopathy.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-001975-30-NL |
| ClinicalTrials.gov | NCT02556203 |
| CCMO | NL55198.018.15 |