Symptomatic peripheral artery disease

Primary efficacy objective:  to evaluate whether rivaroxaban added to acetylsalicylic acid (ASA) is superior to ASA alone in reducing the risk of major thrombotic vascular events (defined as myocardial infarction (MI), ischemic stroke, cardiovascular (CV) death, acute limb ischemia (ALI), and major amputation of a vascular etiology) in symptomatic PAD patients undergoing lower extremity revascularization procedure. Secondary efficacy objectives:  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 allcause mortality.

Xarelto tablet

Rivaroxaban

tablet

2.5

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 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.
The primary safety outcome will be major bleeding events according to the
Thrombolysis in Myocardial Infarction (TIMI) classification.

Main inclusion criteria are:
 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.

Main exclusion criteria are:
 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