ABSORB BTK TRIAL
A prospective single arm registry of the Absorb Everolimus-eluting bioresorbable vascular scaffold in below the knee atherosclerotic arterial lesions

Critical limb ischemia (CLI) is the most advanced stage of peripheral arterial
occlusive disease (PAOD). The incidence of CLI is estimated at 500-1000
patients in a European or North American population of 1 million. The most
important risk factors for developing CLI are diabetes mellitus, smoking, age >
65 year and dyslipidaemia. CLI patients also demonstrate increased rates of
coronary and cerebral artery disease. CLI is associated with a high rate of
major amputations. A major amputation is not only a radical and mutilating
operation, it is also a substantial risk for mortality in this high-risk group
of patients. After 1 year only 50% of patients is alive and free from major
amputation. [Norgren 2007] Revascularisation will decrease the amputation rate
and consequently the mortality rate.

CLI is often resulting from diffuse multisegment disease. Both above- and
below-the-knee (BTK) stenoses and occlusions should be treated in CLI patients.
Several reports suggest patent infrapopliteal or tibial arteries positively
affect the patency rates after femoro-popliteal interventions. [Davies 2008]
and limb salvage rates [Peregrin 2010]. In patients with diabetes, arteries
proximal to the knee joint are often spared or moderately diseased. In these
patients the majority of occlusions occur at the tibial peroneal trunk and
distally. [Norgren 2007]

Invasive treatment consists of open bypass surgery, endovascular
revascularization or a combination of both techniques (hybrid). Especially
endovascular revascularization is increasingly popular, because of the minimal
invasive approach in this frail group of patients. The major limitation of BTK
percutaneous transluminal balloon angioplasty (PTA) alone is its durability.
[Romiti 2008] Improved techniques have been investigated and especially drug
eluting stents [Bioni-Zoccai 2009] and balloons [Liistro 2013] show promising
results.

Reproducible data on the efficacy of drug eluting stents (DES) in
infrapopliteal lesions are available. Up to now three randomized controlled
trials (RCT) have been published. The Achilles trial compared the Cypher Select
(Cordis, Johnson & Johnson, Warren, New Jersey, USA) drug-eluting stent with
PTA. [Scheinert 2012] The Yukon and Destiny trials compared the Yukon
(Translumina, Hechtingen, Germany)) and the Xience (Abbott Vascular, Santa
Clara, California, USA) drug-eluting stents with a bare-metal stent. [Rastan
2011, Bosiers 2012] In all three studies DES showed significantly improved
patency rates at 12 months. A meta-analysis of the three randomized controlled
trials showed an improved 1-year patency rate of 80.0 vs 58.5%. [Katsanos 2013]
All three studies included short and focal lesions (longest mean lesion length
was 31mm in the Yukon trial), despite the fact that the Achilles trial protocol
allowed inclusion of lesions to a length of 120mm.

The Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) system
(Abbott Vascular, Santa Clara, California, USA) resorbs naturally in the body,
leaving no permanent scaffold. The scaffold is composed by poly-L-lactide,
which is covered by a thin layer of amorphous matrix of poly-D,L-lactide that
controls the release of the anti-proliferative drug everolimus. This unique
scaffold has been designed for revascularization of coronary arteries. After
gradual, but full resorption of the scaffold, the target vessel may restore to
a more natural state. Scaffold degradation leads to the loss of radial support,
which occurs 1 year after implantation, while the whole resorption progress is
completed within 3 years. [Oberhauser 2009] Since 2008 CE approval has been
obtained for coronary arteries and since then thousands of patients have been
treated successfully using the Absorb scaffold. Two small single arm coronary
trials (ABSORB A and B) have been published and the ABSORB-EXTEND registry aims
to recruit 1000 patients. [Dudek 2012, Diletti 2013, Muramatsu 2013] The study
design for a large coronary RCT has been published in November 2012 (ABSORB
II). [Diletti 2012] The Absorb scaffold has not yet been used in infrapopliteal
lesions.

As mentioned before, DES is associated with improved patency rates in BTK
lesions. On the other hand, after complete elution of the drug the remaining
stent may promote atherosclerosis. The presence of a foreign body within the
artery induces vascular inflammation, improving the risk for
neoatherosclerosis. [Nakazawa 2011] The increased rigidity of a stent seems
also to disturb flow, alter its pulsatile profile and affect shear stress
within the stent. [Tortoriello 2004] In mobile arteries, like the distal part
of the tibial arteries, stents are at risk for fracturing. In the
femoro-popliteal segment a stent fracture is an independent factor associated
with restenosis. [Iida 2011] Complete resorption of the Absorb scaffold may be
an important feature to obtain long-term patency rates in these arteries.

The aim of this study is to evaluate the efficacy, and feasibility of the
Absorb drug-eluting bioresorbable vascular scaffold in infrapopliteal
hemodynamically significant arterial stenoses and occlusions.

The primary objective is in-stent restenosis at 12 months, defined as lumen
narrowing > 50% assessed by angiography.

Prospective, single-arm, multicentre clinical trial.

Follow-up will be obtained at the outpatient clinic 1, 6 and 12 months after
the intervention. During follow-up any complications will be registered and
physical examination of the treated limb will be performed. Prior to the
follow-up visit at 6 and 12 months, all patients will be analysed by treadmill
test and duplex of the treated artery. At 12 months of follow-up a diagnostic
catheter guided angiography will be performed.

The Absorb everolimus-eluting BVS system (Abbott Vascular, Santa Clara,
California, USA) will be used in the endovascular treatment of symptomatic
tibial atherosclerotic lesions.

Reproducible data on the efficacy of drug eluting stents (DES) in
infrapopliteal lesions are available. Up to now three randomized controlled
trials (RCT) have been published. The Achilles trial compared the Cypher Select
(Cordis, Johnson & Johnson, Warren, New Jersey, USA) DES with PTA. [Scheinert
2012] The Yukon and Destiny trials compared the Yukon (Translumina, Hechtingen,
Germany) and the Xience (Abbott Vascular, Santa Clara, California, USA) DES
with a bare-metal stent. [Rastan 2011, Bosiers 2012] In all three studies DES
showed significantly improved patency rates at 12 months. A meta-analysis of
the three randomized controlled trials showed an improved 1-year patency rate
of 80.0 vs 58.5%. [Katsanos 2013]

As mentioned before, DES is associated with improved patency rates in BTK
lesions. On the other hand, after complete elution of the drug the remaining
stent may promote atherosclerosis. The presence of a foreign body within the
artery induces vascular inflammation, improving the risk for
neoatherosclerosis. [Nakazawa 2011] The increased rigidity of a stent seems
also to disturb flow, alter its pulsatile profile and affect shear stress
within the stent. [Tortoriello 2004] In mobile arteries, like the distal part
of the tibial arteries, stents are at risk for fracturing. In the
femoro-popliteal segment a stent fracture is an independent factor associated
with restenosis. [Iida 2011] Complete resorption of the Absorb scaffold may be
an important feature to obtain long-term patency rates in these arteries.

Please, see the Investigator Brochure, paragraph 8.1 to 8.3 for benefit and
risk assessment of investigational device.

Major complications, like haemorrhage, distal embolization, femoral nerve
palsy, renal failure, pseudoaneurysm and arteriovenous fistula formation, occur
in approximately 0.5% to 2% of patient undergoing angiography via common
femoral artery puncture. [Hessel 1981] However, following a diagnostic
angiography using 4F sheaths the complication rate seems much lower. In a RCT
comprising 110 patients undergoing a diagnostic angiography using 4F sheaths or
catheters only 2 small (<2cm) hematomas and 1 patient with temporary
puncture-site oozing, which did not change the ambulatory status, were
observed. [Dowling 2002]