ESPRIT BTK Development and Status of BRS Clinical Trials for Endovascular Applications - CRTonline
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
ESPRIT BTK Development and Status of BRS Clinical
Trials for Endovascular Applications
Richard J. Rapoza, PhD
DVP of Global Clinical Affairs
Abbott Vascular
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.
Richard J. Rapoza, PhD
Full time employment:
Abbott Vascular
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.
CLI challenges and treatment objectives
Patients with CLI are often faced with the grim possibility of limb amputation due to non-healing
wounds leading to gangrene and infection
• Amputations are associated with 40% mortality rate at 1 year1
• Only 40% regain mobility2
Goals of revascularization:
• Acute:
– Maximize/Restore in-line flow to the distal vasculature to improve perfusion of ischemic tissue
– Minimize acute vessel recoil
• Long term:
– Enhance wound-healing
– Maintain patency to prevent recurrence and need for re-intervention
– Enable future re-treatment if necessary
1. Duff, S., et al. Vasc Health and Risk Mgt. 2019; 15: 187-208.
2. Norgren, L. J Vasc Surg. 2007; 45: S5-S67
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.
BTK therapy hypothesis
Clinical challenges
• Small vessels need to maximize • Long diffuse lesions
luminal gain
• Calcium acts as barrier for rapid drug absorption and
• Acute recoil lesion preparation creates potential for dissections
IDEAL TREATMENT FOR BTK ADDRESSES THREE MAIN NEEDS
1
DRUG
2
SCAFFOLD
3
TEMPORARY
Inhibit neointimal hyperplasia Resist recoil/negative remodeling Leave nothing behind
Top right: representative photomicrograph of porcine coronary artery 48 months post implant with Absorb BVS
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.
All current treatment options for BTK have
inherent limitations
CURRENT TREATMENT OPTIONS FOR TIBIAL CIRCULATION TO EFFECTIVELY TREAT BTK DISEASE:
ANGIOPLASTY
• Elastic recoil Drug Scaffold Leave nothing
BMS • Restenosis (inhibit NIH) (resist recoil) behind
• Restenosis • Dissection
• No on-label BMS (US) • Primary patency 20-50% (TASC II)
• Permanent implant
• Short lengths
Angioplasty ✓
• Surgical reintervention
Atherectomy ✓
DCBs
• Elastic recoil
• Residual plaque DCB ✓ ✓
DES • Dissection
• Failed RCTs
✓
• No on-label DES (US)
• No approved DCB (US) BMS
• Permanent implant
• Short lengths
• Surgical reintervention
ATHERECTOMY DES ✓ ✓
• Device variability
• Embolization
• Lack of data UNMET NEED ✓ ✓ ✓
Adapted from Varcoe, R., LINC 2020 NIH: Neointimal hyperplasia
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.
DCBs have so far failed to provide any
long-term benefit over PTA in BTK disease
LUTONIX‡ BTK IDE STUDY
PRIMARY SAFETY ENDPOINT PRIMARY EFFICACY ENDPOINT
30-DAY FREEDOM FROM MALE-POD COMPOSITE ENDPOINT*
NON-
TIME DCB PTA DIFFERENCE
INFERIORITY
POINT % (95% CI)1 (95% CI)2 (95% CI)2 p-value3
99.3% 99.4% -0.1%
30 days
Meta-analysis showed benefits of DES in BTK1
TASC II GUIDANCE2
“The preponderance of evidence for
infrapopliteal DES, has demonstrated
significant benefit over both BMS
and PTA for (1) patency (2) reduced
reinterventions, (3) reduced amputation,
and (4) improved event-free survival.”
Vessel support (scaffolding) AND
anti-proliferative drug are needed
But many clinicians do not want to
leave a permanent implant behind
And DES are not approved for BTK in the U.S.
1. Fusaro, M., et al. J Am Coll Cardiol Intv 2013;6:1284–93. 2. TASC II Supplement, Jaff et. al . Journal of Endovascular Therapy. 2015.
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.
Treatment hypothesis
TO EFFECTIVELY TREAT BTK DISEASE
Inhibit NIH Resist recoil Leave nothing behind
UNMET NEED ✓ ✓ ✓
DRUG SCAFFOLD TEMPORARY
Sustained drug elution Support the vessel to Bioresorbable
over ~90 days resist recoil scaffold
Polymer drug coating to minimize
downstream particulate
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.
Proof of Concept
CONSECUTIVE PATIENTS TREATED WITH THE CORONARY
ABSORB™ BVS IN HOSPITALS IN SINGAPORE, U.S. AND AUSTRALIA
DEMOGRAPHICS (%) N=125 LESION LOCATION (%) N=156
Male 51.2 P3 5.51
Rutherford Score ATA 35.43
3 15.7 TPT 36.22
4 8.7 PTA 33.07
5 55.9 PA 25.20
6 19.7 Lesion Length (mm)
TASC Mean 25.49
A 21.3 Min 4.00
B 15.7 Max 88.00
C 14.2 Scaffold (mm) N=189
D 8.7 No. of scaffolds deployed (N) 189
NA 43.3 Mean Diameter 3.20
Diabetes 55 Mean Length 25.5
Varcoe, R., LINC 2020 CAUTION: Investigational device. Limited by Federal law to investigational use only.
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.
Primary Patency and TLR
PRIMARY PATENCY
12 months: 91.1%
24 months: 88.6%
FREEDOM FROM TLR
12 months: 96.6%
24 months: 94.5%
Varcoe, R., LINC 2020
CAUTION: Investigational device. Limited by Federal law to investigational use only.
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.ESPRIT™ BTK Everolimus eluting resorbable scaffold
PORCINE MODEL
PDLLA RESORBABLE PLLA RESORBABLE
EVEROLIMUS
COATING SCAFFOLD*
100 µg/cm2 dose density Uniform drug delivery 99 µm strut thickness†
Baseline
Elution rate matched to Provides sustained drug elution Balloon expandable
restenosis cascade to maximize long term patency
without downstream
particulates
Cytostatic; broad therapeutic Resists recoil; provides a
range platform for sustained drug
delivery
CAUTION: Investigational device. Limited by Federal law to investigational use only. 1 Month
*Platinum markers at proximal and distal ends remain for angiographic visualization
† 3.0 mm size; 3.5 mm – 3.75 mm sizes have 120 µm strut thickness Data and images on file at Abbott Vascular
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.LIFE-BTK randomized multicenter trial
PIVOTAL INVESTIGATION OF SAFETY AND EFFICACY OF ESPIRIT™
BTK TREATMENT – BELOW THE KNEE
Safety Endpoint:
6-MONTH MALE+POD
Prospective, randomized multicenter, PRIMARY
US and OUS single-blind, trial ENDPOINTS Efficacy Endpoint:
225 patients randomized Primary Patency + Limb Salvage
2:1 ESPRIT™ BTK vs. PTA
5-YEAR FOLLOW-UP
TRIAL LEADERSHIP
Ramon Varcoe MBBS, MS, FRACS, PhD; Sahil Parikh MD, FACC, FSCAI; Brian DeRubertis MD, FACS
CAUTION: Investigational device. Limited by Federal law to investigational use only.
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.LIFE-BTK trial
Critical Limb
Ischemia
RB 4-5 Maximum 2 de novo/restenotic
Proximal 2/3 of native
(from prior PTA) infrapopliteal lesions,
infrapopliteal arteries
each with ≥70% stenosis
LIFE-BTK
Study
Population Maximum target lesion length:
Maximum 3 scaffolds in
100 mm; maximum total scaffold
target lesion
length among all lesions: 170 mm
RVD ≥ 2.5 mm and 3.75 mm
Varcoe, R., LINC 2020
CAUTION: Investigational device. Limited by Federal law to investigational use only.
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.The Everolimus eluting resorbable scaffold may
address the unmet needs of BTK treatment
TO EFFECTIVELY TREAT BTK DISEASE
Drug Scaffold Leave
(inhibit NIH) (resist recoil) nothing behind
ANGIOPLASTY ✓
ATHERECTOMY ✓
DCB ✓ ✓
BMS ✓
DES ✓ ✓
EVEROLIMUS-ELUTING
RESORBABLE ✓ ✓ ✓
SCAFFOLD
CAUTION: Investigational device. Limited by Federal law to investigational use only. NIH: Neointimal hyperplasia
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.CAUTION: This product is intended for use by or under the direction of a physician. Prior to use, reference the Instructions for Use inside the product carton (when available) or at
eifu.abbottvascular.com or at medical.abbott/manuals for more detailed information on Indications, Contraindications, Warnings, Precautions and Adverse Events.
Illustrations are artist’s representations only and should not be considered as engineering drawings or photographs. Photo(s)
on file at Abbott.
Abbott
3200 Lakeside Dr., Santa Clara, CA. 95054 USA, Tel: 1.800.227.9902
™ Indicates a trademark of the Abbott Group of Companies.
‡ Indicates a third party trademark, which is property of its respective owner.
www.cardiovascular.abbott
©2020 Abbott. All rights reserved. SE2948683 Rev. A
Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.Thank you Not to be reproduced, distributed or excerpted. © 2020 Abbott. All rights reserved. SE2948683 Rev A.
You can also read
