In this study, the main clinical hypothesis is that the TIMI clinically significant bleeding rates will not be different between the rivaroxaban and VKA treatment strategy groups at Month 12.
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Objective
The primary objective of this study is to assess the safety of 2 rivaroxaban
treatment strategies and a dose-adjusted vitamin K antagonist (VKA) treatment
strategy after PCI (with stent placement) in subjects with paroxysmal,
persistent, or permanent non-valvular AF, based on the composite of
Thrombolysis in Myocardial Infarction (TIMI) major bleeding, minor bleeding,
and bleeding requiring medical attention events (known collectively as
clinically significant bleeding) after 12 months of therapy.
Secondary outcome
Secondary Objectives
The secondary objectives are to explore the differences between the treatment
groups in terms of:
* TIMI major bleeding, minor bleeding, and bleeding requiring medical attention
events
* the composite and each component of adverse cardiovascular events
(cardiovascular death,
myocardial infarction [MI], and stroke)
* stent thrombosis events
* TIMI major bleeding, minor bleeding, and bleeding requiring medical attention
events, and the
composite and each component of adverse cardiovascular events (cardiovascular
death, MI, and stroke) at the end of intended dual antiplatelet therapy (DAPT)
period
Background summary
Rivaroxaban (JNJ-39039039, BAY-59-7939) is a potent and highly selective oral
direct factor Xa (FXa) inhibitor. Activation of factor X to FXa plays a central
role in the cascade of blood coagulation.
Current European guidelines for treatment with anticoagulant therapy following
percutaneous coronary intervention (PCI) in patients with atrial fibrillation
(AF) rely on limited retrospective data and provide weak recommendations for
treatment. In North America, there is no separate guideline for treating
patients with AF following PCI, only a consensus paper that highlights the lack
of randomized studies.The American Heart Association (AHA)/American College of
Cardiology (ACC) AF Guidelines suggest use of acetylsalicylic acid (ASA) and
either clopidogrel or warfarin. The 2007 AHA/ACC Unstable Angina/Non-ST-Segment
Elevation Myocardial Infarction (NSTEMI) Guidelines provide a brief
recommendation based on expert opinion and highlight a lack of prospective
research in this patient population. Results from a recent study indicate that
in patients undergoing PCI, the effect of using a single antiplatelet treatment
(clopidogrel) in combination with an oral anticoagulant therapy was associated
with significantly less bleeding and mortality without increasing the risk of
ischemic stroke or stent thrombosis, than when a combination of 2 antiplatelet
treatments were used. Therefore, a randomized study of rivaroxaban treatment
following PCI in patients with paroxysmal, persistent, orpermanent non-valvular
AF will provide significant information on the management of anticoagulant
therapy in these patients.
Study objective
In this study, the main clinical hypothesis is that the TIMI clinically
significant bleeding rates will not be different between the rivaroxaban and
VKA treatment strategy groups at Month 12.
Study design
This is an open-label, randomized, multicenter clinical study assessing the
safety of 2 rivaroxaban treatment strategies and one VKA treatment strategy in
men and women, 18 years of age and older, who
have paroxysmal, persistent, or permanent non-valvular AF and have had a PCI
with stent placement.
A target of 2,100 subjects will be randomized into the study, with
approximately 700 subjects in each treatment strategy group. The randomization
will be stratified by the intended duration of DAPT (1, 6, or 12 months).
Eligible subjects will be randomly assigned in a 1:1:1 ratio to 1 of 3
treatment strategy groups described in the Dosage and Administration section.
The study consists of a screening phase, a 12-month open-label treatment phase,
and an
end-of-treatment/early withdrawal visit. The total duration of participation in
the study for each subject is approximately 12 months.
Intervention
Group 1: Rivaroxaban 15 mg once-daily treatment strategy (12 months)
Group 2: Rivaroxaban 2.5 mg twice-daily treatment strategy (with prespecified
duration of
DAPT 1, 6, or 12 months)
Group 3: VKA treatment strategy (with prespecified duration of DAPT 1, 6, or 12
months)
Study burden and risks
For adverse events for Rivaroxaban and VKA, see informed consent form (regular
risks and bleeding risks).
Risks from having blood draws may include a temporary bruise or *black and
blue mark* . Very rarely, the vein may become inflamed or infected. Fainting,
and in rare cases infection, may occur.
There is a bleeding risk with the treatment of this patient population. To
minimize potential safety risks, subject safety will be closely monitored by
the DMC throughout the study. there is an extensive adverse event data
currently available for rivaroxaban.
Turnhoutsebaan 30
Beerse 2340
BE
Turnhoutsebaan 30
Beerse 2340
BE
Listed location countries
Age
Inclusion criteria
Have a documented medical history of paroxysmal, persistent, or permanent non-valvular AF ;Have undergone PCI procedure (with stent placement) for primary atherosclerotic disease;Be willing and able to adhere to the prohibitions and restrictions specified in this protocol
Exclusion criteria
* Has any condition that contraindicates anticoagulant or antiplatelet therapy or would have an unacceptable risk of bleeding, such as, but not limited to: platelet count <90,000/*L at screening; history of intracranial hemorrhage, 12 month history of clinically significant gastrointestinal bleeding, non-VKA induced elevated PT at screening;* Has anemia of unknown cause with a hemoglobin level <10 g/dL (<6.21 mmol/L) ;* Has a history of stroke or TIA;* Has calculated CrCl <30 mL/min at screening or prerandomization;* Has known significant liver disease or liver function test (LFT) abnormalities;* Has any severe condition that would limit life expectancy to less than 12 months
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 | EUCTR2012-001491-11-NL |
| CCMO | NL42697.094.13 |