STENTYS Coronary Stent System Clinical Trial in Patients with Acute Myocardial Infarction

Bare Metal Stents in Acute Myocardial Infarction
Coronary artery disease continues to be the most common cause of morbidity and
mortality in the occidental world. Originally, coronary angioplasty alone had
been successfully used to treat the symptoms of this condition but was
associated with a high rate of restenosis (30% to 50%), necessitating repeat
revascularization procedures1. Treatment of coronary atherosclerotic disease
has been significantly advanced by interventional cardiology, and in particular
the advent of coronary arterial stents. In comparison to angioplasty alone,
stents have reduced the incidence of angiographic as well as clinical
restenosis, the recurrence of angina, the need for coronary arterial bypass
graft (CABG) surgery, the need for repeat revascularization and the occurrence
of major adverse cardiac events (MACE)2-4.
According to data from NHANES 2005*2008 (NCHS; unpublished NHLBI tabulation),
the overall prevalence for MI is 3.1% in US adults over 20 years of age. MI
prevalence is 4.3% for men and 2.2% for women. Among non-Hispanic whites, MI
prevalence is 4.3% for men and 2.1% for women. Among non-Hispanic blacks, MI
prevalence is 4.3% for men and 2.2% for women. Among Mexican Americans, MI
prevalence is 3.0% for men and 1.1% for women5. On the basis of pooled data
from the FHS, ARIC, and CHS studies of the NHLBI, within 1 and 5 year after a
first MI, 19% and 36% of men, and 26% and 47% of women aged > 45, will die.
Differences also exist between subjects from different ethnical backgrounds: at
over 65 years of age, 25% of white men, 30% of white women, 25% of black men,
and 30% of black women will die within a year after a first MI. These
differences exist for 5 year outcomes as well (21% of white men and women, 33%
of black men, and 26% of black women)5
Acute myocardial infarction (AMI) is usually the consequence of thrombotic
occlusion of a major epicardial coronary artery. Mechanical reperfusion with
percutaneous coronary intervention (PCI) can reduce myocardial damage,
reinfarction, heart failure, and death. In a meta-analysis of RCTs comparing
BMS to balloon angioplasty in subjects with acute myocardial infarction,
stenting was associated with reduced rates of reocclusion (6.7% vs. 10.1%, OR
0.62, 95% CI 0.40 to 0.96, p = 0.03) and angiographic restenosis (23.9% vs.
39.3%, OR 0.45, 95% CI 0.34 to 0.59, p<0.001), as well as a reduction in target
vessel revascularization (TVR; 12.2% vs. 19.2%, OR 0.50, 95% CI 0.37 to 0.69,
p<0.001)5.
Currently, the Multi-Link stent is the only bare-metal stent licensed in the US
for treating subjects with acute MI.
Despite the apparent successes, problems remain due to failure to achieve
optimal stent apposition and normal myocardial reperfusion. Early stent
malapposition may be due to incomplete expansion or undersizing of
balloon-expandable stents. Several studies have emphasized the importance of
early malapposition in the setting of ST elevation MI, in which substantial
thrombotic burden and the presence of diffuse vasoconstriction may be
contributory. The incidence of incomplete stent deployment and undersizing is
between 20% and 30% when assessed by angiography and even higher when IVUS is
used for assessment6,7. It was recently demonstrated that identification of
stent undersizing by visual estimate is a strong predictor of stent
thrombosis6; this was usually caused by severe calcification, high thrombotic
burden with subsequent vasoconstriction or incorrect judgment of the true
coronary vessel size by the performing operator 6-10. An intravascular
ultrasound sub study of the HORIZONS-AMI trial enrolled 241 subjects with 263
native coronary lesions (201 PES, 62 BMS) with baseline imaging.
Post-intervention acute stent malapposition (ASM) occurred in 40.3% BMS-treated
lesions11. In a recent analysis, early stent thrombosis found in autopsies of
subjects who suffered acute coronary disease and were implanted with either BMS
or DES in the 30 days prior to their death, were significantly associated with
stent malapposition12.
The STENTYS Coronary Stent System includes a self-expanding bare metal
(nitinol) stent on a rapid exchange (RX) delivery system. In view of the
theoretical implications of malapposition, the self-expanding property may
offer a potential benefit.
The APPOSITION II study compared the STENTYS Coronary Stent System with a
balloon-expandable stent in AMI, with the primary endpoint of malapposition at
3 days per OCT. The study demonstrated that subjects treated with
balloon-expandable stents had three times higher percentage of malapposed
struts immediately after the procedure. At 3 days, 0.58% of struts were
malapposed in the STENTYS Coronary Stent System group under OCT vs. 5.46% in
the balloon-expandable group, representing a 10-fold reduction. On a
per-patient basis, 13.9% in the self-expanding stent group vs. 37.1% in the
balloon-expandable group had malapposed stents (defined as *5% malapposed
struts) immediately after the procedure; at 3 days, none of the subjects in the
self-expanding stent group vs. 28% in the balloon-expandable group had
malapposed stents (p < 0.001).
Improvement in acute apposition may also translate into lower rate of 30-day
major adverse cardiac events (MACE). In HORIZONS-AMI, MACE occurred in 5.5% of
subjects13. In the APPOSITION III post market registry (N=1002), evaluating the
long term clinical benefit of the STENTYS stent for AMI with ST-elevations
(STEMI) in a real-life setting, 30-day MACE was 3.5%. (G. Amoroso, Euro PCR,
May 18, 2012)
In the current study we aim to assess the safety and effectiveness of the
STENTYS Coronary Stent System compared with the Multi-Link Stent with respect
to the primary endpoint of target vessel failure and a powered secondary
endpoint of acute apposition.

To evaluate the safety and effectiveness of the STENTYS Coronary Stent System
in the treatment of de novo stenotic lesions in coronary arteries in subjects
undergoing primary revascularization due to Acute ST Segment Elevation
Myocardial Infarction (STEMI) as compared to the Multi-Link bare metal coronary
stent platform (Abbott Vascular, Inc.).

This study is designed as a prospective, multicenter, randomized controlled
trial to assess the effectiveness and safety of STENTYS Coronary Stent System
in the treatment of de novo stenotic lesions in coronary arteries in subjects
undergoing primary revascularization due to AMI as compared with Multi-Link
Coronary Stent Platform (Abbott Vascular).

Subjects undergoing primary revascularization for acute myocardial infarction
(AMI) will undergo PCI with the STENTYS Coronary Stent System in the treatment
group and the Multi-Link stent in the control group, randomized in 2:1 ratio.
Enrollment will include 880 subjects (586 in the STENTYS group and 294 in the
control group) at up to 60 sites worldwide (a minimum of 50% North American
subjects will be planned).
A maximum of 50 subjects will be enrolled at any one site.
A 10% drop-out rate of subjects is assumed, resulting in 792 evaluable subjects
(528:264).

Subjects will be randomized to undergo PCI with the STENTYS Coronary Stent
System or Multi-Link stent using a centralized randomization process and
stratified by site. Random-block size randomization will be used.

The secondary powered endpoint (ASM) will be assessed by IVUS at the time of
the index stent implantation, in the first 212 (141:71) consecutively enrolled
subjects (the IVUS cohort).

Late angiographic and IVUS endpoints will be assessed in the 105 subjects out
of IVUS cohort, at 12-13 months after the index procedure, and after assessment
of the clinical TVF endpoint (2:1 STENTYS:Multi-Link).
Early and late OCT endpoints will be assessed in a sub-study of 60 subjects
from the IVUS cohort, consecutively enrolled at selected sites with OCT
capability.

Adjudication of study endpoints will be determined by an independent clinical
events committee (CEC). The CEC will rule on all deaths throughout the study
and will adjudicate the occurrence of clinical study endpoints and reports of
device failures in accordance with the definitions pre-specified within this
protocol. CEC members will be blinded to treatment group.

Review of safety data and risks to subjects will be monitored by an independent
data safety monitoring board (DSMB) at pre-specified enrollment milestones. The
DSMB is charged with assuring patient safety during the course of the study and
may, among other things, recommend that the study should be stopped if the data
demonstrates that subjects are at an unacceptable risk of harm due to their
study participation. The DSMB may determine that additional meetings and data
review are necessary and will notify the sponsor, STENTYS Inc., if additional
meetings are requested by DSMB members.

Stent Placement Procedure

An angiogram (x-ray film of the heart) will be performed. The angiogram
procedure will start with a needle puncture in either your groin, or wrist,
after the area is numbed with a local anesthetic. A thin and flexible wire and
catheter (a long thin hollow tube) will be used to inject contrast dye (a
liquid that makes your heart vessels visible on x-ray) into your arteries, and
then a device similar to an x-ray machine will be used to locate the narrowing
in your artery. You may feel a warm sensation from the dye, but this feeling
will usually go away after a few minutes.
Your artery must be sufficiently open to proceed with the intervention.
Therefore, if a blood clot is present, a thrombectomy catheter may be used to
remove the clot from the obstructed artery (thrombus aspiration). A small
flexible catheter will then be passed through your arteries to the narrowed
region in the heart. If required, your doctor will use a small balloon to make
the artery a bit larger prior to implanting the stent. The stent is then
implanted by withdrawing a sheath that covers the stent (if you have a STENTYS
stent implanted) so that the stent expands, or by inflating a balloon and
pressing the stent against the artery wall (if you have a Multi-Link Vision
stent implanted). After the stent is implanted, your doctor may choose to
inflate a balloon within the stent to help the stent fully expand
(post-dilation). The exact procedure will be performed according to your
doctor*s usual practice. At the end of the procedure, the catheter will be
removed, leaving just the stent in place. Another angiogram will be
performed.

At the end of the procedure, the catheters and wires are removed and you will
lie flat for a period of time determined by your doctor. After the procedure,
you will be monitored in the hospital until hospital discharge. Additional ECGs
and routine blood tests will be performed during your stay at the hospital.
You will be required to take the same medications usually given to all patients
that receive a stent. These medications are aspirin (which will be for the rest
of your life) and/or clopidogrel, prasugrel, or ticlopidine for at least 12
months.

You may also be asked to sign a separate informed consent for the PCI procedure.

If you are one of the first 212 subjects enrolled into the study, you will
undergo intravascular ultrasound (IVUS) right after your stent has been
implanted. If you are amongst the 120 subjects enrolled at an IVUS-designated
site, you will be asked to have another angiogram and intravascular ultrasound
(IVUS) within one month of your 12 month visit. Of these 120 patients
undergoing angiography and IVUS, 60 patients will undergo OCT (Optical
Coherence Tomography Imaging) which is an additional medical imaging procedure
to determine how well a stent has healed. With IVUS and OCT, a tiny catheter
is inserted into a coronary vessel, which allows your physician to see images
inside the coronary arteries. The primary benefits of IVUS and OCT are that
these methods provide added detail of the inside of the artery, the diameter
(width) of the artery, information about the plaque in the walls of the artery,
and how the stent is positioned against the wall of the artery

RISKS AND DISCOMFORTS

Risks Associated with cardiovascular stent implantation in coronary arteries

There are risks associated with the placement and use of stents. Some of the
potential complications include:
* Death
* Abrupt coronary vessel closure or spasm (involuntary contraction)
* Allergic/anaphylactoid reaction to procedural medications (anticoagulant,
antithrombotic, etc.) or contrast medium
* Allergic reaction to stent components (nickel)
* Aneurysm (widening of a blood vessel), pseudoaneurysm (widening that looks
like an aneurysm), or arteriovenous fistula (abnormal passage)
* Arrhythmia (the heart may beat irregularly or stop beating completely)
* Atrial fibrillation (one of the chambers of the heart may beat irregularly)
* Balloon rupture
* Bleeding
* Cardiac tamponade (compression of the heart caused by blood or fluid
accumulation in the space between the myocardium [the muscle of the heart] and
the pericardium [the outer covering sac of the heart])
* Cardiogenic shock (the heart is unable to pump enough blood for the needs of
the body)
* Cerebral vascular accident (damage to the blood vessels of the brain caused
by a clot or bursting of a blood vessel)
* Dissection (tear in the layers of the walls) of the coronary arteries or the
aorta
* Embolism (air, tissue, device or thrombus)
* Hematoma (mass of blood in the tissues) at the access site
* Hypotension (low blood pressure)/hypertension (high blood pressure)
* Insertion site infection (an infection of the hole in leg artery where the
device was inserted into your body)
* Ischemia/infarction of tissue/organ (loss of blood flow to tissues or organs)
* Kidney damage
* Limb ischemia (loss of blood flow to the leg)
* Device failure or malfunction (failure to place to the stent or to place
stent at the intended site)
* Myocardial infarction (heart attack)
* Perforation (a hole or injury to the heart or blood vessels)
* Renal failure (the kidneys cease to work correctly)
* Restenosis (returned to narrowing) of the stented artery
* Sepsis (massive infection throughout the body)
* Total occlusion (blockage) of the coronary artery
* Transfusion (receiving blood to replace lost blood)
* Unstable angina (unexpected chest pain not related to physical activity)
* Vasospasm (blood vessel spasms which lead to narrowing of the blood vessels)
* Transient ischemic attack (temporary loss of blood to parts of your brain
that does not cause permanent damage)
* Vascular injury (injury to the blood vessels)

Obtaining blood can cause pain, bleeding, bruising, or swelling at the site of
the needle stick. Fainting sometimes occurs and infection rarely occurs.

IVUS and OCT may be associated with added risk, including injury to the artery
or blood clot formation. The added risk is less than 1%.

Important Information for Women If you are female, this procedure and/or
treatments may involve unforeseeable risks to the embryo or fetus should you be
pregnant at the time of treatment. If you are female, you will not be enrolled
in the study if you are pregnant or might become pregnant. If you are of child
bearing potential you must have a negative pregnancy test at the time of
baseline procedures.


POSSIBLE BENEFITS IF YOU JOIN THIS STUDY

It is possible that there may be no direct benefit to you as a consequence of
participating in this study and receiving this device, but the device may be
able to help heart function and might stabilize your condition during and/or
after the heart procedure.