dr. ashok seth - meril life · fortis escorts new delhi dr. ashok seth 06 apollo chennai dr. samuel...

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