4. Clinical study
PROGRESS-AMS
Study design
▪ Prospective, multi-center, consecutive,
non-randomized First In Man (FIM) trial
!
Primary endpoint (reached)
▪ MACE *at 4 months <30 %
!
Results (at 4 months)
▪ LLL 1.08 mm
▪ TLR 23.8%
!
Conclusion
▪ Bare AMS (Absorbable magnesium
Scaffold) concept is safe and feasible
▪ Need for prolonged scaffolding time and
an anti-proliferative drug
Long-term FUP (~7 yrs)
Clinical, angiographic, IVUS
4-month FUP
Clinical, angiographic, IVUS
63 patients enrolled at 8 international
clinical sites
6-month clinical FUP (n=61)
12-month clinical FUP (n=60)
Source: Erbel et al. Lancet 2007; 369: 1869–75.
Waksman et.al, JACC Cardiovasc Interv 2009;2:312-320
* Composite of cardiac death, nonfatal MI, ischemia driven TLR
5. Lessons learned from the bare AMS
PROGRESS-I showed the bare AMS concept to be safe and
feasible
Optimization of device with prolonged
scaffolding time and an anti-proliferative drug
Improvements for future AMS
Loss of scaffolding
area (55%)
In-stent
neointima (45%)
Post implantation 4 month follow-up
Contribution to
lumen loss
!Source: Erbel R. et al., Lancet 2007;369:1869-75.
Waksman et.al, JACC Cardiovasc Interv 2009;2:312-320.
Results:
▪ LLL 1.08 mm
▪ TLR 23.8%
7. 1
6
pts
withdrew
consent
for
imaging
FUP
(2
at
6-‐month
and
4
at
12-‐month
FUP)
2
1
pt
died
a
non-‐cardiac
death
(Cohort
1).
2
pts
withdrew
consent
(1
Cohort
1
and
1
Cohort
2)
3
1
pt
died
of
a
non-‐cardiac
death
1
pt
withdrew
consent
46
patients
with
de
novo
coronary
artery
stenosis
Mandatory
6mo:
Clinical
FUP
(n
=
22)
Imaging
FUP
(n
=
201)
Cohort
1
(n
=
22) Cohort
2
(n
=
24)
Optional
6mo:
Clinical
FUP
(n
=
24)
Imaging
FUP
(n
=
16)
Mandatory
12mo:
Clinical
FUP
(n
=
232)
Imaging
FUP
(n
=
201)
Optional
12mo:
Clinical
FUP
(n
=
202
)
Imaging
FUP
(n
=
13)
Mandatory
24mo:
Clinical
FUP
(n
=
202)
Mandatory
24mo:
Clinical
FUP
(n=24)
Clinical study
BIOSOLVE-I
Study design
▪ Prospective, multi-center First In Man
(FIM) trial. Single, de novo lesions
3.0-3.5mm and ≤ 12mm long
!
Primary endpoints
Cohort 1: TLF at 6 months
Cohort 2: TLF at 12 months
!
Source:
M
Haude.
et
al.
Lancet
2013;
381:836-‐44.
Mandatory
36mo:
Clinical
FUP
(n
=
203)
Mandatory
36mo:
Clinical
FUP
(n=24)
8. BIOSOLVE-I study results
6-and 12-month late lumen loss (LLL)
6-‐month
LLL
0.64
±
0.50
mm
12-‐month
LLL
0.52
±
0.39
mm
LLL
of
the
bare
AMS
in
the
PROGRESS
study
at
4-‐month:
1.08
±
0.49
mm
Cumulative
Frequency
(%)
In-‐scaffold
LLL
(mm)
M Haude. et al. Lancet 2013; 381:836-44.
9. BIOSOLVE-I study results
Six to 36-month clinical & angiographic follow-up
Device Success 100% (47/47)
Procedure Success 100% (46/46)
Clinical Results 6-Month 12-Month 24-Month 36-Month
TLF 4.3% (2/46) 6.8% (3/44) 6.8% (3/44) 6.8% (3/44)
Cardiac death 0.0% 0.0% 0.0% 0.0%
MI2 0.0% 2.3% (1/44) 2.3% (1/44) 2.3% (1/44)
Scaffold Thrombosis 0.0% 0.0% 0.0% 0.0%
TLR (clinically driven) 4.3% (2/46) 4.5% (2/44) 4.5% (2/44) 4.5% (2/44)
In-scaffold LLL 0.64 ± 0.50 mm 0.52 ± 0.39 mm NA NA
1 M Haude. et al. Lancet 2013; 381:836-44. 2 Target vessel peri-procedural MI. 3 TLR occurred during 6M FUP, both pts had angina. 1 pt received an additional
DREAMS during the initial procedure due to a flow-limiting bailout. 4 LLL not available at 24-month as no imaging FUP was performed
5 M Haude, oral presentation EuroPCR 2013. 6 R Waksman, oral presentation EuroPCR 2014.
11. Conclusions
▪ DREAMS demonstrates an excellent safety profile up to 12 months
▪ A TLF rate of 7.0% at 12 months after DREAMS implantation is similar to the
results of ABSORB (7.1%; Cohort B)
▪ DREAMS demonstrated significantly improved efficacy at 12 months compared
to the bare AMS:
▪ Reduction in LLL of 61% compared to the 4-month data of the bare AMS
(1.08 vs. 0.52 mm)
▪ Reduction of TLR rate by 82% (26.7 vs. 4.7%)
▪ The late lumen loss remained stable between 6-and 12-month follow-up
▪ Vasomotion and natural vessel angulation were completely restored at 6-
month follow-up
13. The
Lancet,
published
online
September
1,
2014
BIOSCIENCE
publicado
en
the
Lancet,
incluye
un
metaanálisis
con
BIOFLOW-‐II
14. META-‐ANALYSIS
OF
BIOSCIENCE
AND
BIOFLOW
II
Risk
ratio
(95%
CI)
Favours
BP
SES
Favours
DP
EES
Target
lesion
failure
Bioflow-‐II
Bioscience
Overall
Cardiac
death
Bioflow-‐II
Bioscience
Overall
Target
vessel
myocardial
infarction
Bioflow-‐II
Bioscience
Overall
Target
lesion
revascularisation
Bioflow-‐II
Bioscience
Overall
BP
SES DP
EES
0.82
(0.41-‐1.64)
0.98
(0.71-1.35)
0.95
(0.71-1.27)
19/298
69/1,063
12/154
70/1,056
1.03
(0.09-11.31)
0.90
(0.50-1.64)
0.91
(0.51-1.63)
2/298
20/1,063
1/154
22/1,056
1.03
(0.32-3.38)
0.96
(0.59-1.58)
0.97
(0.62-1.53)
8/298
30/1,063
4/154
31/1,056
0.74
(0.29-1.90)
1.51
(0.90-2.54)
1.18
(0.61-2.30)
10/298
35/1,063
7/154
23/1,056
0.25
0.5
1
2
4
Risk
ratio
(95%
CI)
BIOSCIENCE
confirma
los
resultados
de
BIOFLOW-‐II
en
una
gran
población
de
pacientes
más
compleja.
Especialmente
para
los
criterios
de
valoración
más
dificiles:
IM
y
muerte
.
16. At the beginning
T
=
0:
Immediately
following
scaffold
deployment
▪ Drug
starts
to
elute
▪ No
signs
of
degradation
in
coating
or
metalT = 0
Vascular restoration therapy: Bioabsorption in
single steps
17. Vascular restoration therapy:
Bioabsorption in single steps
Second phase
T
=
1
month
▪ Drug
elutes
from
the
polymer
▪ Healing
begins
with
minimal
tissue
growth
▪ The
magnesium
core
starts
to
corrode
and
converts
gradually
to
Mg-‐oxide
T = 1 month
18. Vascular restoration therapy:
Bioabsorption in single steps
T = 3 months
Third phase
T
=
3
months
▪ Drug
elution
is
completed
▪ Magnesium
is
further
corroded
and
converted
to
Mg-‐
oxide.
Bioabsorption
of
Mg
has
not
yet
started
▪ Struts
are
mostly
covered
with
tissue
19. Vascular restoration therapy:
Bioabsorption in single steps
T
=
9
months
▪ Magnesium
core
is
fully
converted
into
Mg
oxide.
Mg
oxide
converts
to
hydroxyapatite
▪ Cracks
appear
and
are
infiltrated
by
SMCs;
material
is
getting
bioabsorbed
T = 9 months
Fourth phase
20. Vascular restoration therapy:
Bioabsorption in single steps
T
=
1
year
▪ Most
of
the
scaffold
material
has
been
bioabsorbed
T = 1 year
Fifth phase
21. Vascular restoration therapy:
Bioabsorption in single steps
T
=
1.5+
years
▪ All
foreign
material
is
gone,
only
cells
are
left
▪ Vessel
has
returned
to
its
natural,
healed
state
T = 1.5 years
Completed
22. 121 patients with de novo coronary
artery stenosis
1 month Clinical FUP
6 month Clinical FUP
Angiographic FUP (mandatory)
IVUS / OCT (Subgroup only)
Vasomotion (if patient consents)
12 month Clinical FUP
Angiographic FUP (voluntary)
IVUS / OCT (Subgroup only)
Vasomotion (if patient consents)
3 year, Clinical FUP
2 year, Clinical FUP
DESIGN
▪ Prospective, multi-center, FIM. Single de novo
coronary artery lesions in up to two coronary
arteries, RVD between 2.2-3.8 mm and ≤ 21
mm long
!
PRIMARY ENDPOINT
▪ In-scaffold late lumen loss @ 6-month
!
COORDINATING CLINICAL INVESTIGATOR
▪ Prof. M.Haude, Lukaskrankenhaus GmbH,
Neuss, Germany
!
CORELAB
▪ Cardialysis, Rotterdam, The Netherlands
BIOSOLVE-II Study Design
23. Post-dilatation capability of DREAMS scaffold
DREAMS crimped (3.0mm nominal) Expansion to 3.0mm
Over expansion to 5.0mm
24. Potential for side branch access
Kissing balloon inflation:
MB 3.0 mm / SB 2.5 mm
D = 1.3mm
5.5mm
*Experimental, N=1
Experimental* post-dilatation of DREAMS shows potential
side-branch access
25. Coating integrity of DREAMS
SEM images of expanded 3.0 mm DREAMS (expansion diameter 3.5 mm)
SEM images of expanded 3.0 mm DREAMS
(expansion diameter 4.25 mm)
26. Summary
▪ Magnesium offers an ideal balance between biocompatibility,
mechanical performances and absorption
▪ The Biotronik absorbable Mg program is most advanced:
- BIOSOLVE-I has proven safety of DREAMS 1. generation with
Paclitaxel elution and improved efficacy compared to the bare
AMS version
- BIOSOLVE-II is currently testing safety and efficacy of DREAMS
2. generation with Sirolimus elution
!
▪ In about a year we will have the DREAMS-2 available in our shelfs
if the BISOLVE II trial gets the primary endpoint in terms of
efficacy and safety
27. PK Papyrus
Covered coronary stent system
Indicated for acute coronary artery
perforations
29. VIHQReleaseFebr.19,2014
1.57
1.19
Crossing profile
[mm diameter]
Data on file at BIOTRONIK; * Ø 2.5-4.0 mm
6F
5F
24% reduction
Guide catheter
compatibility*
Jostent Graftmaster 3.0/16
Sandwich design
PK Papyrus 3.0/15
Covered single stent design
Covered single stent design allows for low crossing profile
and 5F guide catheter compatibility*
30. VIHQReleaseFebr.19,2014
High flexibility and low crossing profile for exceptional
deliverability – allowing you to seal perforation with confidence
Nmm²
0 27,5 55 82,5 110
Bending stiffness of crimped stent
58% reduction
Jostent Graftmaster
3.0/16
PK Papyrus
3.0/15
Data on file at BIOTRONIK
Expect PK Papyrus to deliver like a conventional stent
Track Force in coronary artery model [N]
0,0
0,6
1,3
1,9
2,5
Distance [mm]
0 50 100 150 200
53% reduction
in maximum
track force
PK Papyrus 3.0/20
Jostent Graftmaster 3.0/19
PRO-Kinetic Energy 3.0/20
51. Confidential–forinternaluseonly
Conclusión
▪ Papyrus es un dispositivo que se convierte en un MUST en las
estanterías de las salas de hemodinamica para evitar complicaciones
graves, ya que tiene una alta capacidad de sellado coronario
▪ Es un dispositivo cuyo performance es equivalente al BEST IN
CLASS de los DES de última generación
▪ No hay que utilizar catéteres guía de mayor perfil
▪ Pasa perfectamente por un GuideLiner de 6F
▪ El performance del stent queda patente en los casos testados
▪ La comprobación al año da idea de la eficacia y seguridad del
dispositivo
51
