The primary efficacy objective of the study is:* to evaluate whether rivaroxaban added to ASA is superior to ASA alone in reducingthe risk of major thrombotic vascular events (defined as MI, ischemic stroke, CVdeath, ALI, and major amputation of a…
ID
Source
Brief title
Condition
- Platelet disorders
- Vascular therapeutic procedures
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy outcome variable will be a composite endpoint
consisting of the time from randomization to the first occurrence of any of the
following major thrombotic vascular events: MI, ischemic stroke, CV death,
ALI, and major amputation due to a vascular etiology.
The primary safety outcome will be major bleeding events according to the
Thrombolysis in Myocardial Infarction (TIMI) classification.
Secondary outcome
The secondary efficacy variables of the study will be:
* time from randomization to the first occurrence of an index limb
revascularization;
* time from randomization to the first occurrence of MI, ischemic stroke,
coronary heart disease mortality, ALI, and major amputation of a
vascular etiology;
* time from randomization to the first occurrence of MI, ischemic stroke,
all-cause mortality, ALI, and major amputation of a vascular etiology;
* time from randomization to the first occurrence of hospitalization for a
coronary or peripheral cause (either lower limb) of a thrombotic nature;
* time from randomization to the first occurrence of MI, all-cause stroke,
CV death, ALI, and major amputation of a vascular etiology;
* time from randomization to the first occurrence of venous
thromboembolic (VTE) events;
* time from randomization to the first occurrence of all-cause mortality
Background summary
PAD refers to the atherosclerotic obstruction of the major arteries supplying
the lower
extremities, sometimes also referred to as lower extremity artery disease.
Atherosclerosis of
the peripheral circulation, with underlying atheroma and chronic inflammation,
leads to
progressive occlusion of medium and large arteries, with additional risks of
embolism or
thrombus formation. Abrupt occlusions and plaque rupture may lead to acute
complications
such as acute limb ischemia (ALI), similar to an acute coronary syndrome in the
coronary
circulation.
It is now well established that symptoms, severity, and acuteness of PAD are
major
determinants of subsequent risk of cardiovascular (CV) events and mortality.
Independent of
symptoms, patients diagnosed with PAD are at an increased risk of subsequent
myocardial
infarction (MI) and stroke, and are 6 times more likely to die within 10 years
than those
without PAD.
The most common initial symptom from underlying progressive atherosclerotic
occlusion of
the peripheral vasculature is leg pain on exertion or intermittent claudication.
Overall, the currently available treatment options for PAD and evidence-based
knowledge on
certain patient subsets are suboptimal. Given that the prevalence of
conventional
cardiovascular risk factors for PAD is increasing, it is likely that the
incidence of PAD would
grow even more dramatically overtime. The loss of mobility, functional decline,
and
cardiovascular events, represents a major public health challenge. New and
effective
treatments are urgently needed to reverse these trends
Study objective
The primary efficacy objective of the study is:
* to evaluate whether rivaroxaban added to ASA is superior to ASA alone in
reducing
the risk of major thrombotic vascular events (defined as MI, ischemic stroke, CV
death, ALI, and major amputation of a vascular etiology) in symptomatic PAD
patients with a recent lower extremity revascularization procedure.
The primary safety objective of the study is:
* to evaluate the overall safety and tolerability of rivaroxaban added to ASA
compared
to ASA alone.
The secondary efficacy objectives of the study are:
* to evaluate whether rivaroxaban added to ASA is superior to ASA alone in
reducing
the risk of index limb revascularization;
* to evaluate whether rivaroxaban added to ASA is superior to ASA alone in
reducing
the risk of MI, ischemic stroke, coronary heart disease mortality, ALI, and
major
amputation of a vascular etiology;
* to evaluate whether rivaroxaban added to ASA is superior to ASA alone in
reducing
the risk of MI, ischemic stroke, all-cause mortality, ALI, and major amputation
of a
vascular etiology;
* to evaluate whether rivaroxaban added to ASA is superior to ASA alone in
reducing
the risk of vascular hospitalizations for a coronary or peripheral event
(either limb) of
a thrombotic nature;
* to evaluate whether rivaroxaban added to ASA is superior to ASA alone in
reducing
the risk of MI, all-cause stroke, CV death, ALI, and major amputation of a
vascular
etiology;
* to evaluate the efficacy of rivaroxaban in reducing the risk of venous
thromboembolic
(VTE) events;
* to evaluate the efficacy of rivaroxaban in reducing the risk of all-cause
mortality.
Study design
This study is an international multicenter, randomized, placebo-controlled,
double-blind,
event-driven phase 3 study.
Intervention
Study treatment assignment will be double-blind. Study treatment consists of
study
medication (rivaroxaban or matching placebo) in addition to study ASA, which is
also
dispensed by the study.
Study burden and risks
Due to the event-driven study design, no firm treatment duration can be
stipulated for an individual patient. However, the mean treatment duration is
estimated to be approximately 30 months and the maximum treatment period
for an individual patient to be approximately 42 months.
Kaiser Wilhelm Alle NA
Leverkusen 51368
DE
Kaiser Wilhelm Alle NA
Leverkusen 51368
DE
Listed location countries
Age
Inclusion criteria
age *50,
* documented moderate to severe symptomatic lower extremity
peripheral artery occlusive disease as evidenced by ALL of the
following:
a. clinically, by functional limitations in walking activity, ischemic
rest pain or ischemic ulceration,
b. anatomically, by imaging evidence of arterial occlusive disease
below the inguinal ligament within 6 months prior to or at the
time of the qualifying revascularization,
AND
c. hemodynamically (within 6 months prior to, or at the time of, the
qualifying revascularization) by:
* an ABI * 0.80 or TBI * 0.60 of the index leg (in the event of
non-compressible ankle arteries) for patients without a prior
history of limb revascularization on the index leg,
OR
* an ABI * 0.85 or TBI * 0.65 of the index leg (in the event of
non-compressible ankle arteries) for patients with a prior
history of limb revascularization on the index leg.
Exclusion criteria
- patients undergoing revascularization for asymptomatic PAD, mild
claudication without functional limitation or major tissue loss
(including severe ischemic ulcers or gangrene) of the index leg,
- patients undergoing revascularization of the index leg to treat an
asymptomatic or minimally symptomatic restenosis of a bypass graft
or target lesion restenosis,
- prior revascularization on the index leg within 8 weeks of the
qualifying revascularization,
- Planned dual antiplatelet therapy (DAPT) use for the qualifying
revascularization procedure of clopidogrel in addition to ASA for
>30 days after the qualifying revascularization procedure
- Planned DAPT use for any other indication(s) with any P2Y12
antagonists in addition to ASA after the qualifying revascularization
procedure
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 | EUCTR2014-005569-58-NL |
| CCMO | NL54528.101.15 |