Post on 25-May-2018
MeRes-1 One Year Clinical & CTA Results with a thin-strut PLLA based MeRes100 – Sirolimus Eluting BioResorbable
Vascular Scaffold System in patents with CAD
Dr. Ashok Seth FRCP, FACC, FSCAI, DSc.
For The MeRes-1 Investigators
EuroPCR 2017, Evolving BRS Technology Tuesday 16th May 2017, 13:05 – 13:18, Room 351, Level-3
Speaker’s Name: Dr. Ashok Seth
I have the following potential conflicts of interest to report:
• Honorarium: Abbott Vascular, Meril Life Sciences • Consultant: Abbott Vascular, Meril Life Sciences
Background
• BRS is a revolutionary therapy with a potential to transform the treatment of coronary artery disease.
• First generation of BRS are not ‘user friendly ’ and hence difficult to apply to the real world patient population – Thick struts, high profile
– Special tips and tricks of implantation
– Limited expansion characteristics
– Limited accessibility to side branches
– Low radiopacity
– Uncertain radial strength
– Concerns regarding scaffold thrombosis
NEXT GENERATION Devices Are Needed !
MeRes100 (developed in INDIA) Sirolimus Eluting Bioresorbable Vascular Scaffold
100 micron strut thickness
MeRes100 – BRS Strut Thickness & Crossing Profile
6Fr Guide Catheter
for all Øs Average profile of 1.2mm for 3.00 mm Ø
OCT images courtesy of Dr. Daniel Chamié, Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil. Data on file with Meril Life Sciences Pvt. Ltd.
Absorb 150μm
100 μm
MeRes100 100μm 90
100
120
150 150
125 125
150
60
80
100
120
140
160
Stru
t Th
ickn
ess
(μm
)
Strut Thickness Comparison
1.2 1.2
1.34 1.44 1.43
1.68
1.3
1.75
1
1.2
1.4
1.6
1.8
Cro
ssin
g P
rofi
le (
mm
) Crossing Profile Comparison
MeRes100 – BRS Radiopacity
Data on file with Meril Life Sciences Pvt. Ltd.
• Enhanced visibility. Gives a sense of virtual tubing. High operator comfort.
• Couplets of Tri-Axial RO markers (Pt) at either end of the scaffold
Absorb 3.00mm
MeRes100 3.00mm
Proximal markers
Distal markers
MeRes-1 Study Design
N = 108 30-days 6-months# 1-year 2-years 3-years
First-in-Human Safety and Effectiveness in Patients with Single,
De-novo Coronary Lesion (in up to 2 vessels) treated by a Single
MeRes100 Scaffold up to 24mm length in 108 pts
Clinical follow-up
*QCA, IVUS, OCT & CTA follow-up
CLINICAL FOLLOW-UP 108 108 108 108 108
ANGIOGRAPHIC FOLLOW-UP - 36 - 36 -
OCT FOLLOW-UP - 12 - 12 -
IVUS FOLLOW-UP - 12 - 12 -
CTA FOLLOW-UP - - 12 - -
Diameters – 2.75, 3.00 and 3.50 mm Lengths – 19 and 24 mm DAPT – Minimum 1 year
*Pre-designated sites & patients consent. #6-months data presented during TCT 2016 by Dr. Ashok Seth
6-months# 1-year
Major Endpoints
• Safety – Primary Endpoint:
• MACE (Cardiac death, MI*, ID-TLR, ID-TVR) at 6 mo
– Secondary Endpoints:
• MACE at 1 Yr
• Device & procedure success
• Scaffold thrombosis (ARC defined) at 6 mo and 1 Yr
• Effectiveness QCA (6 Mo) : Late lumen loss (in-scaffold / in-segment)
OCT (6 Mo) : Minimum lumen area (flow area), NIH area
IVUS(6 Mo) : Scaffold & lumen area, %VO
CTA (1 Yr ) : Mean/minimal lumen, plaque & vessel area; Area stenosis; % Cross sections with calcified, mixed & non-calcified plaque
* Definition of MI – includes all Myocardial Infarction • 6-months data (QCA, OCT and IVUS) presented during TCT 2016 by Dr. Ashok Seth
Study Organisation
• PI – Dr. Ashok Seth, Fortis Escorts, New Delhi
• Co-PI – Dr. Praveen Chandra, Medanta, Gurugram
• Co-PI – Dr. Vinay K. Bahl, AIIMS, New Delhi
• Core Labs – Angiographic – Cardiovascular Research Center, Sao Paulo
– IVUS / OCT /CTA – Cardialysis, Rotterdam
• CRO – Data Management – JSS, New Delhi
108 Subjects, 16 Investigating Sites Investigating Site City Investigator # Enrolled
Jayadeva Bangalore Dr. C. N. Manjunath 23
LTMG Mumbai Dr. Ajay Mahajan 20
Max New Delhi Dr. Viveka Kumar 13
SGPGI Lucknow Dr. P. K. Goel 11
Medanta The Medicity Gurugram Dr. Praveen Chandra 10
AIIMS New Delhi Dr. Vinay K. Bahl Dr. Sundeep Mishra
07
Hero DMC Ludhiana Dr. G. S. Wander 07
Fortis Escorts New Delhi Dr. Ashok Seth 06
Apollo Chennai Dr. Samuel Mathew Dr. G. Sengottuvelu
04
Sree Chitra Trivandrum Dr. Ajit Kumar V. K. 03
Fortis Vasant Kunj New Delhi Dr. Upendra Kaul 02
GB Pant New Delhi Dr. Vijay Trehan 01
Apollo Jubilee Hills Hyderabad Dr. P. C. Rath 01
Investigating Sites
Baseline Demographics
Variable N = 108
Age, years (mean ± SD) 50.1 ± 9.3
Male 71%
Current Smoker 17%
Diabetes mellitus 28%
Dyslipidemia 13%
Hypertension 42%
Myocardial Infarction (> 7days) 34%
Clinical presentation
- Stable Angina 52%
- Unstable Angina 34%
- Silent Ischemia 14%
LVEF, % (mean ± SD) 50.6 ± 10.0
Lesion Characteristics & Procedure
Variable 108 pts | 116 lesions
LAD | LCx | RCA 60% | 11% | 29%
Calcification: mild | moderate | severe 8% | 2% | 4%
Tortuosity: moderate | severe 9% | 2%
SB ≥ 2 mm (visual estimation) 29%
Lesion class: A | B1 | B2 | C 7% | 32% | 56% | 5%
Baseline TIMI 3 flow 97%
Lesions per patient 1.07 ± 0.35
Nominal scaffold diameter: 2.75 | 3.0 | 3.5 mm 11% | 51% | 38%
Nominal scaffold length: 19 | 24 mm 65% | 35%
High pressure postdilatation 100%
Device | Procedure success 100% | 99%*
*One patient received a metal DES to cover a proximal dissection during post dilatation.
108 patients and 116 lesions
*6-months data presented during TCT 2016 by Dr. Ashok Seth. $ ARC defined criteria. @ Myocardial Infarction defined as per WHO criteria. # Death due to aminophylline induced anaphylactic shock.
Clinical Endpoint at 1-Year
Clinical Endpoint MACE, n (%)
In-Hospital N = 108 (100%)
1-month N = 108 (100%)
6-months* N = 108 (100%)
1 Year N= 107 (99%)
MACE Composite of- 0 (0%) 0 (0%) 0 (0%) 1 (0.93%)
Cardiac Death 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Myocardial Infarction@ 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Ischemia-driven TLR 0 (0%) 0 (0%) 0 (0%) 1 (0.93%)
Ischemia-driven TVR 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Scaffold Thrombosis$ 0 (0%) 0 (0%) 0 (0%) 0 (0%)
Non-cardiac death 0 (0%) 0 (0%) 1# (0.9%) 0 (0%)
100% monitored / CEC adjudicated
QCA Analysis 6-months FU*
N = 41 Lesions Baseline Post-procedure 6-months
Lesion length (mm) 12.13 ± 3.77 - -
In-segment RVD (mm) 3.07 ± 0.39 3.03 ± 0.41 2.94 ± 0.38
In-scaffold RVD (mm) - 3.14 ± 0.38 3.06 ± 0.39
In-segment MLD (mm) 0.95 ± 0.38 2.67 ± 0.38 2.53 ± 0.40
In-scaffold MLD (mm) - 2.82 ± 0.32 2.67 ± 0.40
In-segment acute gain (mm) - 1.71 ± 0.50 -
In-scaffold acute gain (mm) - 1.86 ± 0.42 -
In-segment DS (%) 68.75 ± 11.9 11.66 ± 8.1 13.87 ± 9.6
In-scaffold DS (%) - 10.02 ± 6.5 12.68 ± 8.5
*6-months data (QCA, OCT and IVUS) presented during TCT 2016 by Dr. Ashok Seth
Late Lumen Loss (LLL) 6-months FU*
*6-months data (QCA, OCT and IVUS) presented during TCT 2016 by Dr. Ashok Seth
0.15 ± 0.23
0.14 ± 0.22
0.07 ± 0.29 0.06 ± 0.15
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
0.18
0.2
In-Scaffold In-Segment Proximal Edge Distal Edge
Late
Lu
men
Lo
ss (
mm
)
DES like Late Lumen Loss (LLL)
Restenosis 0%
Quantitative Assessment of OCT 6-months FU*
*6-months data (QCA, OCT and IVUS) presented during TCT 2016 by Dr. Ashok Seth
N = 13 Post-procedure 6-months Delta p value
Mean Flow area (mm2) 7.20 6.87 -0.33 0.283
Minimum Flow area (mm2) 6.13 5.06 -1.07 0.001
Mean Abluminal Scaffold area (mm2) 8.04 8.47 +0.43 0.241
Minimum Abluminal Scaffold area (mm2) 7.00 6.83 -0.13 0.458
Mean strut core area (mm2) 0.14 0.11 0.03 0.003
Mean neointimal area: on top & in-between struts (mm2) - 1.53 - -
% Covered struts - 99.3%
Serial Quantitative IVUS Analysis 6-months FU*
*6-months data (QCA, OCT and IVUS) presented during TCT 2016 by Dr. Ashok Seth
N = 12 Post-procedure 6-months Delta p value (BL-6M)
Mean Lumen area (mm2) 6.14 6.25 +0.10 0.64
Mean Scaffold area (mm2) 6.17 6.47 +0.30 0.122
Mean Vessel area (mm2) 13.4 13.4 +0.07 0.915
NIH area (mm2) 0.14
% Volume obstruction - 2.53% -
Minimum lumen area (mm2) 5.08 4.81 -0.28 0.332
Minimum scaffold area (mm2) 5.10 5.25 +0.14 0.478
Case Example 53y/M | Diabetic | Hypertensive | No family history | Non-smoker | Stable angina
Diagnostic Angio Final Result MeRes100 3.50 x 19 mm
Baseline OCT 6-month f/up 6-month OCT f/up
Data on file.
Software: Aquarius iNtuition ver 4.4 (TeraRecon)
• Coronary segmentation
• Center lumen line
• Scaffold segment and Prox/dist 5-mm references were analyzed
• Min, mean, max lumen/vessel area
• Area stenosis, in-scaffold
• Corelab: Cardialysis
Quantitative CT Angio : 1 Year
5 mm prox
5 mm Distal
Scaffold segment
Cross-sectional analysis
Case Example
In-scaffold segment
Mean Lumen Area: 4.65 mm2
Minimum Lumen Area: 3.55 mm2 Mean Vessel Area: 10.13 mm2 Area Stenosis: 39% Mean Plaque Area: 5.47 mm2
CTA 1-year Follow-up
*One patient received a metal DES to cover a proximal dissection during post dilatation.
CTA Analysis 1-Year FU
# European Heart Journal – Cardiovascular Imaging (2017) 00, 1-10. Onuma Y et al. CTA Core Lab – Cardialysis, Rotterdam, The Netherlands. Dr. Yoshinobu Onuma & Prof. Patrick W. Serruys.
*One patient received a metal DES to cover a proximal dissection during post dilatation.
N=12 MeRes100 1-Year FU
Mean vessel area, mm2 12.92 ± 3.37
Mean lumen area, mm2 5.68 ± 1.97
Minimum lumen area, mm2 4.27 ± 1.32
Minimum plaque area, mm2 5.55 ± 1.24
Mean lumen diameter, mm 2.65 ± 0.43
Minimum lumen diameter, mm 2.31 ± 0.36
Mean area stenosis, % 11.33 ± 26.57
Cross sections with mixed plaque, % 3.24 ± 8.36
Cross sections with non-calcified plaque, % 96.76 ± 8.36
Cross sections with calcified plaque, % 0
Proximal mean lumen area, mm2 5.64 ± 1.76
Distal mean lumen area, mm2 4.42 ± 1.82
*One patient received a metal DES to cover a proximal dissection during post dilatation.
CTA Analysis 1 YR FU
# European Heart Journal – Cardiovascular Imaging (2017) 00, 1-10. Onuma Y et al. CTA Core Lab – Cardialysis, Rotterdam, The Netherlands. Dr. Yoshinobu Onuma & Prof. Patrick W. Serruys.
*One patient received a metal DES to cover a proximal dissection during post dilatation.
N=12 MeRes100 1-Year FU
Mean vessel area, mm2 12.92 ± 3.37
Mean lumen area, mm2 5.68 ± 1.97
Minimum lumen area, mm2 4.27 ± 1.32
Minimum plaque area, mm2 5.55 ± 1.24
Mean lumen diameter, mm 2.65 ± 0.43
Minimum lumen diameter, mm 2.31 ± 0.36
Mean area stenosis, % 11.33 ± 26.57
Cross sections with mixed plaque, % 3.24 ± 8.36
Cross sections with non-calcified plaque, % 96.76 ± 8.36
Cross sections with calcified plaque, % 0
Proximal mean lumen area, mm2 5.64 ± 1.76
Distal mean lumen area, mm2 4.42 ± 1.82
Absorb 18 Months#
12.40 (9.20 to 15.0)
4.94 (3.83 to 6.30)
3.60 (2.83 to 4.58)
23.2 (11.42 to 32.55)
17.4 (0 to 56.67)
81.8 (41.14 to 100)
0
4.53 (3.64 to 5.87)
4.07 (3.33 to 5.43)
Lumen Area (mm2)
Cu
mu
lati
ve
In
cid
en
ce
Ra
te
Cumulative frequency distribution curve of mean lumen area and minimal lumen area in scaffold segment at 12 months
Mean Lumen Area 5.7 ± 2.0 mm2
Minimal Lumen Area 4.3 ± 1.3 mm2
%AS 43%
• MeRes-1 trial for the first in human evaluation of the thinner strut
2nd generation scaffold : MeRes100 – BRS demonstrated high
acute success, very low MACE ( 0.93% , 1 ID-TLR) and no Scaffold
Thrombosis up to 1-year follow-up.
• Multimodality Vascular Imaging are consistent in demonstrating
high efficacy of MeRes100 – BRS up to 1 year
– QCA at 6 Months: Low late lumen loss (0.15 ± 0.23 mm)
– OCT at 6 Months: Virtually complete strut coverage (99.3%)
– IVUS at 6 months: Sustained mean flow area and very low %VO (2.53%)
– CTA at 1 year: Low mean area stenosis 11.33 ± 26.57%
Conclusion
• These encouraging results of MeRes-1 study provide the basis for
further studies, using a wider range of lengths and sizes in more
complex and larger patient population.
• MeRes-1 Extend clinical trial (N = 64) currently recruiting in multiple
sites in Europe, Asia, South Africa and South America.
• 1:1 Randomized pivotal trial of MeRes100 vs Xience (N = 470) has been
initiated in China:
– PI: Prof. Gao Runlin
– 20 Clinical sites
– 100% QCA follow-up and 20% population with OCT follow-up
• Global (OUS) randomized pivotal trial of MeRes100 vs Xience has been
planned for H2, 2017.
FUTURE TRIALS
MeRes-1 : simultaneous publication on line ahead of print
EuroIntervention, 16 th May 2017