BIOTRONIKS * Acute performance Of a Drug Eluting Absorbable Metal Scaffold (DREAMS 2G) in patients with de Novo Lesions in NatiVE Coronary Arteries: BIOSOLVE-III

In comparison to Bare Metal Stents (BMS), Drug-Eluting Stents (DES) have shown
reduced restenosis rate but have been associated with an increased risk of late
thrombotic events which can*t be limited by prolonged dual antiplatelet therapy
(DAPT). Bioabsorbable Vascular Scaffolds (BVS) have been developed to overcome
the limitations of BMS and DES, and to avoid creation of a permanently caged
vessel segment with inhibited vasomotion and vessel remodeling, chronic vessel
wall inflammation or long-term stent crushing and fractures. Furthermore BVS
provide improved non-invasive vessel lumen imaging by computer tomography or
magnetic resonance technology and facilitate surgical or interventional target
vessel and lesion reintervention.

The first Absorbable Metallic Scaffold (AMS) with magnesium alloy has been
introduced by Biotronik AG as an alternative to polymeric scaffolds. It has a
high mechanical strength and properties comparable to stainless steel stents in
terms of its low elastic recoil (<8%), high collapse pressure (0.8 bar), and
minimal shortening after inflation (<5%)
The AMS device has been improved by using a different magnesium alloy with a
slower degradation time and by changing the strut shape in cross section from
rectangular to square, thus improving scaffolding properties. A drug-polymer
matrix with paclitaxel has been added to inhibit neo-intimal proliferative
response.
The improved AMS: DREAMS (Drug Eluting Absorbable Metal Scaffold) was tested in
the BIOSOLVE-I study. In this prospective, multi-center, first-in-man trial the
DREAMS showed an excellent clinical safety profile with no cardiac death or
scaffold thrombosis up to 12-month follow-up.
However, even so the refinement of the device resulted in significant
improvements compared to the bare AMS and the TLF rates were comparable to
contemporary drug eluting stents and the ABSORB BVS, late lumen loss results
were not comparable to the DES and BVS and required enhancement of the device.
Thus DREAMS 1G was further improved to DREAMS 2G (2nd generation), which has a
more flexible and stronger scaffold backbone design, higher bending
flexibility, and higher radial force. Radiopaque markers were also added for
better x-ray visibility of the scaffold. Furthermore, the drug-polymer coating
has been changed from Paclitaxel to Sirolimus in combination with a
bioresorbable PLLA-polymer to decrease neo-intima formation more effectively.
This same drug-polymer coating is also successfully used in the commercially
available Orsiro sirolimus eluting coronary stent system (Biotronik AG).

DREAMS 2G is currently under investigation in the BIOSOLVE-II study (BIOTRONIK
* Safety and Clinical Performance of the Drug Eluting Absorbable Metal Scaffold
DREAMS 2G in the Treatment of Subjects with de novo lesions in native coronary
arteries). It is the first study to assess the safety and performance of a
novel sirolimus-eluting absorbable magnesium scaffold.
123 subjects have been enrolled from October 2013 to May 2015.
The 6-month results of the BIOSOLVE-II trial are expected later this year.

In order to ensure 6F guiding catheter compatibility, the crossing profile of
the DREAMS 2G has been reduced to 1.5mm.
The BIOSOLVE-III study will be conducted in order to proof easy deliverability
and acute performance in regards to procedure success with the improved DREAMS
2G.
Even so the DREAMS 2G starts to lose its mechanical integrity at around 3
month, studies with the predecessor devices have shown the ability of positive
remodeling at later time points. Since those subject cohorts have been rather
small, results are only indicating the possibility of positive remodeling.
Therefore the BIOSOLVE-III trial aims to assess 12-month LLL, % diameter
stenosis and binary restenosis rate as secondary endpoints in a larger
population

The study objective is to assess the acute clinical performance of the drug
eluting absorbable metal scaffold (DREAMS 2G)

This is a prospective, multi-center trial to be conducted in up to 7
investigational sites.
Up to 61 subjects will be enrolled in order to ensure 60 evaluable study
subjects.
Clinical follow-up visits will take place at 1, 6, and 12 months and annually
until 3 years post procedure.
All subjects will undergo angiographic follow-up at 12months.

Percutaneous transluminal coronary angioplasty (PTCA) including concomitant
anticoagulation medication according to protocol and implantation of the DREAMS
2G scaffold.

The use of the DREAMS scaffold may lead to undesirable effects or discomfort.
The same risks associated with treatment with an authorised stent or balloon
may occur. No increased incidence is expected based on earlier studies with the
preceding product and similar products. Some of the risks can also occur during
the control angiograms at 12 months.

Complications of the heart:
Occlusion of coronary arteries with decreased supply of blood to the heart with
heart attack in extreme cases, re-stenosis (renewed narrowing of a treated
vessel), cardiogenic shock (abnormal function of the heart chamber), chest
pain, cardiac tamponade (accumulation of fluid inside the pericardial space,
adversely affecting the function of the heart), perforation or dissection
(rupture) of the coronary artery, of the aorta or of the heart, emergency heart
surgery, pericardial effusion (abnormal accumulation of fluid inside the
pericardial space), development of an aneurysm (pathological distension of an
artery), death
Cardiac arrhythmias:
Ventricular tachycardia (accelerated heart rate); ventricular or atrial
fibrillation (uncoordinated contraction of the muscle of the heart chambers);
bradycardia (reduced heart rate)
Complications due to the scaffold:
Failure to place the scaffold at the intended site, detachment of the scaffold
from the introduction system, faulty placement of the scaffold, deformation of
the scaffold, embolisation of the scaffold (detachment of the scaffold from the
catheter with subsequent displacement), scaffold thrombosis (formation of a
blood clot inside the scaffold) or occlusion, breaking of scaffold, movement of
the scaffold, insufficient attachment of the scaffold to the vascular wall or
compression of the scaffold, problems while inflating the balloon, rupture or
small hole in the balloon of the introduction system, problems deflating the
balloon, difficulties in retracting the equipment, embolisation (detachment and
displacement) of the catheter material
Events affecting the airways:
Acute pulmonary oedema (accumulation of fluid inside the lungs), heart failure
(inability of the heart to pump a sufficient amount of blood), respiratory
insufficiency or respiratory failure (inability of the lungs to provide enough
oxygen to the tissue)
Events affecting the vessels:
Bruising at the access site, drop / increase in blood pressure, pseudo-aneurysm
(hematoma that forms as the result of a leaking hole in an artery), formation
of arteriovenous fistula (abnormal connection between an artery and a vein),
retroperitoneal (in the posterior abdominal cavity) bruising, rupture or
perforation of the vascular wall, re-stenosis, thrombosis (blood clot inside
the vessel) or occlusion, vascular cramps, disturbed peripheral circulation,
rupture of the vascular wall, distal embolism (occlusion of the vessel due to
material that has become detached from a blood clot)
Bleeding events:
Bleeding at the access site or other bleeding events that require a transfusion
or another form of treatment
Events affecting the nervous system:
Stroke or transient ischemic attack (TIA) of the brain causing neurological
deficits, damage to the nerves
Allergic reactions:
Allergic reactions to the contrast medium, to the platelet aggregation
inhibitor (drug to prevent the formation of blood clots), to the scaffolding
material, to the polymer coating or sirolimus or its breakdown products
There is a possibility of adverse reactions of the body to the medicinal
component of DREAMS. The exceedingly low quantity of sirolimus in blood plasma
means that the classical side effects triggered by the medication are less
relevant than during systemic treatment and occur significantly less
frequently. The following undesirable effects are known: Abnormal liver values,
anaemia (low blood count), joint pains, diarrhoea, hypercholesterolaemia,
hypersensitivity reaction, including anaphylactic reaction,
hypertriglyceridaemia, hypokalaemia (reduced blood potassium level),
infections, interstitial pulmonary disease (disease affecting the tissue of the
lungs), lymphoma or other malignant diseases, thrombocytopenia (platelet
deficiency in the blood)
As with any product, new and previously unknown side effects may occur when
using the test product.
The control angiogram scheduled at 12 months harbours risks or can lead to
discomfort. The use of X-ray radiation is necessary to carry out the angiogram.
Experience with patients receiving similar treatment has shown that the total
additional X-ray radiation lasts between about 5-10 minutes. This corresponds
to a radiation dose of about 4-6 millisievert (mSv; depending on X-ray system
used); as a comparison: the average exposure to natural radiation per year
amounts to about 2.5 mSv.
Please tell the employees of the study staff about all symptoms, diseases or
injuries that occur during the course of the clinical study. If any of these
are serious, inform the study staff immediately, if necessary by telephone.


Potential Benefits:
Compared to a 'normal' permanent stent, the DREAMS scaffold does not remain
inside your coronary arteries but is absorbed over time. You may benefit from
this form of treatment, as it allows the same section of the vessel to be
retreated with a stent at a later point in time without having to apply
multiple layer of stents, or if necessary the vessel can be treated with a
bypass. In addition, the risk of a later blood clot may be reduced, as no stent
remains inside the vessel at which a blood clot could later develop.
Furthermore, inflammation caused by the stent remaining inside the vessel may
be prevented, which could lead to a reduction in the development of new
stenosis (atherosclerosis). Another potential benefit is that lateral branches
that branch off from the narrowing being treated are blocked less or only
temporarily, which in turn improves blood supply to the vessel. As the scaffold
is absorbed over time, the mobility of the vessel is only reduced during the
first 3-4 months. Moreover, non-invasive procedures such as an MRI or CT are
easier to interpret, as there are no artefacts caused by metal; this could help
prevent a potential coronary angiogram at a later point in time. However, as
the function of the test product has not been demonstrated yet, it is also
possible that you will not have the desired benefit from participating in this
clinical study.
In addition, your health will be intensively monitored during the study visits.
The health of your coronary arteries will be assessed as part of the planned
control angiogram, which means that the progression of your disease can be
controlled and newly developing stenosis can be detected and treated
accordingly. Your participation in the study contributes to the development of
potential and improved therapies for patients with atherosclerosis in future.