repairing btk dissection: results from the toba ii btk

21
Repairing BTK dissection: Results from the TOBA II BTK pivotal study George Adams, MD, MHS, MBA, FACC, FSCAI North Carolina Heart and Vascular, Rex Hospital Raleigh, NC

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Page 1: Repairing BTK dissection: Results from the TOBA II BTK

Repairing BTK dissection: Results from the TOBA II BTK pivotal study

George Adams, MD, MHS, MBA, FACC, FSCAI

North Carolina Heart and Vascular, Rex Hospital

Raleigh, NC

Page 2: Repairing BTK dissection: Results from the TOBA II BTK

Disclosure

George Adams

.................................................................................

I have the following potential conflicts of interest to report:

Consulting

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

I do not have any potential conflict of interest

Page 3: Repairing BTK dissection: Results from the TOBA II BTK

Critical Limb Ischemia

1Yost, The Sage Group 20162Zeller, J Am Coll Cardiol 20143Fanelli, J Cardiovasc Surg 2014

4Razavi, J Vasc Interv Radiol 20145Schillinger, Radiology 2002

CLI currently afflicts 2-3.4 million in the US1

• Forecast to exceed 4 million by 20301

Plain angioplasty is standard therapy

• Historically suboptimal results

• 30.7% dissection rate2,3

• Underestimated: medial calcium, bone interference and small RVD4

• Predictor for infrapopliteal restenosis5

No approved implant for BTK in the US

Page 4: Repairing BTK dissection: Results from the TOBA II BTK

Tack Endovascular System®

Tack® Implants• Four pre-loaded nitinol implants

• 6mm deployed length

• Each implant self-sizes to tapering BTK anatomy

– 1.5 – 4.5mm RVD

OTW Delivery System• 4F / .014”

• 150cm working length

• Accurate (≤1mm) deployment

Tack Endovascular System is CE Mark authorized under EC Directive 93/42/EEC.

Adaptive Sizing™ is a trademark of Intact Vascular, Inc.

Tack Endovascular System® and Tack® are registered trademarks of Intact Vascular, Inc.

Caution: Investigational Device

Tack Endovascular System (4F) is limited by Federal (United States) law to investigational use.

Not approved for sale in the United States.

Page 5: Repairing BTK dissection: Results from the TOBA II BTK

TOBA Dissection Repair Trials (N=820)A

TK

TOBA(N=138)

Prospective, single arm13 European sites

Journal of Vascular Surgery1

89.5% 12m K-M Freedom from CD-TLR76.4% 12m K-M patency rate

98.5% Technical success rate

TOBA II(N=213)

Pivotal IDE

Prospective, single arm33 US/European sitesPOBA or Lutonix® DCB

JACC: Cardiovascular Interventions2

86.5% 12m K-M Freedom from CD-TLR79.3% K-M Patency rate

0.5% Bail out stent rate92.1% Dissection resolution

TOBA III(N=201)

Prospective, single arm14 European sites

IN.PACT™ Admiral™

12m data presented at TCT 2019*

97.5% 12m K-M Freedom from CD-TLR95.0% K-M Patency rate

0.6% Bail out stent rate97.7% Dissection resolution

BTK

TOBA BTK(N=35)

Prospective, single arm6 European/New Zealand

sites

Catheterization and Cardiovascular Intervention3

93.5% 12m K-M Freedom from CD- TLR84.5% 12m Amputation-free survival

78.4% K-M Patency rate

TOBA II BTK(N=233)

Pivotal IDE

Prospective, single arm41 US/international sites

First presentation of 6m pivotal data in Europe at LINC 2020

Lutonix® is a registered trademark of BD InterventionalIN.PACT™ and Admiral™ are trademarks of Medtronic, Inc.

1Bosiers, J Vasc Surg 20162Gray, J Am Coll Cardiol: Cardiovasc Interv 20193Brodmann, Cathet Cardiovasc Interv 2018

*12m results from standard lesion group (n =169); an additional 32 patients with long lesions (>15 - ≤25cm) were enrolled and analyzed separately

Page 6: Repairing BTK dissection: Results from the TOBA II BTK

TOBA II BTK Study Design and Endpoints

Prospective, single-arm pivotal IDE study

PopulationPatients with CLI and angiographic evidence of a dissection post-PTA requiring repair in the mid/distal popliteal, tibial and/or peroneal arteries

Enrollment 233 patients at 41 US, international sites

PrimaryEndpoints

・Safety: MALE + POD at 30d・Efficacy: freedom from MALE at 6m + POD at 30d

SecondaryEndpoints

・Tacked segment patency at 6 months (DUS flow/no flow)

・Target limb salvage at 6 months

Key Observational

Endpoints

・Dissection resolution・Freedom from CD-TLR・Target lesion patency

・Changes from baseline:-Rutherford-Wound status-Quality of life

MALE + POD: composite of all-cause death, above-ankle target limb amputation, or major re-intervention to the target lesion(s), defined as new bypass graft, jump/interposition graft revision, or thrombectomy/thrombolysis

BTK

POBA

Dissection?

Screen Failure

NO

YES

Requires

repair?

YES

NO

Tack Endovascular System

introduced (enrolled)30d 6m 12m 24m 36m

Page 7: Repairing BTK dissection: Results from the TOBA II BTK

TOBA II BTK Investigators

Joseph Cardenas

Yuma, AZ

Michael Lichtenberg

Arnsberg, Germany

Christian Wissgott

Heide, Germany

Klaus Hertting

Buchholz, Germany

Ehrin Armstrong

Denver, CO

Marcus Thieme

Sonneberg, Germany

Zoltan Ruzsa

Bacs-Kiskun, Hungary

Robert Staffa

Brno, Czech Republic

Jaafer Golzar

Oak Lawn, IL

Marianne Brodmann

Graz, Austria

Gary Ansel

Columbus, OH

Sundeep Das

St. Louis, MO

Craig Walker

Houma, LA

Peter Soukas

Providence, RI

Bryan Fisher

Nashville, TN

Gaurav Aggarwala

Huntsville, TX

Sashi Kilaru

Cincinnati, OH

Bela Merkley

Budapest, Hungary

Rahul Bose

New Braunfels, TX

Klaus Brechtel

Berlin, Germany

Nicolas Shammas

Davenport, IA

Andrew Holden

Auckland, New Zealand

Jeffrey Carr

Tyler, TX

Vaqar Ali

Jacksonville, FL

Muhammad Khan

McKinney, TX

Jon George

Philadelphia, PA

Ashit Jain

Fremont, CA

Nelson Bernardo

Washington, DC

John Rundback

Teaneck, NJ

Andrew Klein

Atlanta, GA

Thomas Davis

Detroit, MI

Richard Kovach

Browns Mill, NJ

Michael Silva

Galveston, TX

Siddhartha Rao

Raleigh, NC

Robert Attaran

New Haven, CT

Jack Chamberlin

Elk Grove Village, IL

Gabriel Delgado

Matthews, NC

Neil Strickman

Houston, TX

David Dexter

Norfolk, VA

George Adams

Raleigh, NC

Pat Geraghty

St. Louis, MO

Andrej Schmidt

Leipzig, Germany

Angiographic Core Lab / Clinical Events Committee: Yale Cardiovascular Research Group (New Haven, CT)

Duplex Ultrasound Core Lab: VasCore (Boston, MA)

Page 8: Repairing BTK dissection: Results from the TOBA II BTK

TOBA II BTK Key Eligibility Criteria

Key Inclusion

Rutherford 3-5*

RVD 1.5 – 4.5mm, inclusive

P2 to ≥1cm above tibiotalar joint

Post-PTA residual DS <30%, and

≥1 dissection the investigator

would otherwise treat

(i.e., PTA / stenting)

Key Exclusion

WIfI wound / infection score >2

Acute / sub-acute thrombosis and / or

occlusion

Previous bypass / stent in target limb

Severe calcium (visual estimate)

*RC3 excluded with protocol Rev C

Page 9: Repairing BTK dissection: Results from the TOBA II BTK

TOBA II BTK Baseline Patient Characteristics

Mean ± SD (N)

or % (n/N)

Age (y) 74.4 ± 10.0 (233)

Gender

Male 67.4% (157/233)

BMI 28.8 ± 5.6 (231)

BMI ≥ 30 37.2% (86/231)

TBI target limb 0.43 ± 0.23 (117)

Rutherford Class

3 16.3% (38/233)

4 33.5% (78/233)

5 50.2% (117/233)

% (n/N)

Smoking History

Current/Former 62.2% (145/233)

Never 37.8% (88/233)

Diabetes mellitus 65.7% (153/233)

Arterial hypertension 93.6% (218/233)

Coronary artery disease 56.1% (129/230)

MI 22.0% (51/232)

PCI / CABG 43.9% (101/230)

Chronic renal insufficiency 24.1% (56/232)

History of previous

peripheral intervention50.2% (117/233)

(ITT population)

Page 10: Repairing BTK dissection: Results from the TOBA II BTK

TOBA II BTK Baseline Lesion Characteristics

Mean ± SD (N)

or % (n/N)

Lesion type (site reported)

De novo 93.8% (257/274)

RVD (mm)*

Proximal 3.5 ± 1.0 (248)

Distal 2.6 ± 0.7 (248)

Pre-PTA DS % 85 ± 17 (248)

CTO 47.6% (118/248)

Calcification (PARC)

None / mild 64.1% (159/248)

Moderate 18.1% (45/248)

Severe 17.7% (44/248)

Mean ± SD (N)

or % (n/N)

Lesion length (mm)

Target lesion length 80 ± 49 (248)

PTA treated length 154 ± 110 (238)

Most distal target lesion location

P2 4.0% (10/248)

P3 1.2% (3/248)

Tibioperoneal trunk 10.1% (25/248)

Anterior tibial 41.1% (102/248)

Posterior tibial 22.6% (56/248)

Peroneal 21.0% (52/248)

*Protocol specified a balloon-to-vessel ratio of 1:1 (by visual estimate)

(Core lab adjudicated; ITT population)

Page 11: Repairing BTK dissection: Results from the TOBA II BTK

Tack Delivery

Tack Deployment Site

Anterior tibial 44%

Peroneal 18%

Posterior tibial 17%

Tibioperoneal trunk 11%

Popliteal 10%

Tack Procedure % (n/N)

Device success* 96.5% (303/314)

Bail out stent rate 1.3% (3/233)

In Tacked segment 0.4% (1/233)

*successful deployment of the Tack(s) at the intended target site(s) and

withdrawal of the delivery catheter from the introducer sheath (per device)

Prox: 49.1%

Mid: 24.0%

Dist: 14.9%

42

52

177

139

90

101

121

20

17

102

38

15

Anterior

Tibial

Posterior

Tibial

(Core lab adjudicated; ITT population)

# of Tacks placed

in vessel segment#

Page 12: Repairing BTK dissection: Results from the TOBA II BTK

Dissection Resolution

1National Heart Lung and Blood Institute, 1985

Post

A: 21%

B: 39%

C: 12%

D: 27%

E: 1%

Pre-Tack

NHLBI Dissection Grade1

Mean ± SD (N)

Dissections per patient 1.4 ± 0.6 (229)

Dissection length (mm) 24 ± 18 (341)

Tacks per patient 4.0 ± 2.8 (230)

100% of dissections were fully

resolved with Tack placement

(Core lab adjudicated; ITT population)

Page 13: Repairing BTK dissection: Results from the TOBA II BTK

Primary Safety% (n/N)

[97.5% CI]*Performance

Goal1 Endpoint p-value*

MALE + POD at 30d ITT1.3% (3/228)

12.0% MET <0.0001[ - , 3.8%]

Above-ankle amputation 0.9% (2/229)

All-cause death 0.4% (1/229)

Major reintervention to the target lesion 0.0% (0/229)

†Continuity corrected z-test for one proportion. One sided lower 97.5% confidence bound.

Primary Efficacy% (n/N)

[97.5% CI]†

Performance Goal1 Endpoint p-value†

Freedom from

MALE at 6m + POD at 30d

ITT95.6% (196/205)

74.0% MET <0.0001[91.8%, - ]

PP 95.8% (183/191)[91.8%, - ]

*Exact binomial test for one proportion. Confidence interval is the one-sided exact 97.5% upper bound.

MALE + POD: composite of all-cause death, above-ankle target limb amputation, or major re-intervention to the target lesion(s), defined as new bypass graft, jump/interposition graft revision, or thrombectomy/thrombolysis

Primary Endpoints Met

Page 14: Repairing BTK dissection: Results from the TOBA II BTK

6M K-M Tacked Segment and Lesion Patency

87.7%

87.3%

Pate

ncy

(%)

0

10

20

30

40

50

60

70

80

90

100

Time in Days

0 30 60 90 120 150 180 210

DaysTacked Segment Patency (95% CI)

At Risk

30 99.7% (99.0%,100%) 300

180 87.7% (84.0%,91.4%) 264

210 82.1% (77.7%,86.4%)

DaysTarget Lesion

Patency (95% CI)At Risk

30 99.5% (98.5%,100.0%) 196

180 87.3% (82.7%,92.0%) 172

210 81.2% (75.8%,86.7%)

*DUS flow or no flow at 6m; Tacked segment: Tack implant + 5mm of artery proximal and distal; Tacks w/in 1cm are considered same segment†DUS flow or no flow at 6m in PTA treated length

Tacked Segment Patency: 87.7%

Target Lesion Patency: 87.3%

Tacked Segment Patency*

Target Lesion Patency†

(Core lab adjudicated; ITT population)

Page 15: Repairing BTK dissection: Results from the TOBA II BTK

Limb Salvage and Freedom from CD-TLR

98.6%

Fre

edom

fro

m A

mputa

tion (

%)

0

10

20

30

40

50

60

70

80

90

100

Time in Days

0 30 60 90 120 150 180 210

(ITT population)

6m K-M Target Limb Salvage: 98.6%92.0%

Fre

edom

fro

m C

D-T

LR

(%

)

0

10

20

30

40

50

60

70

80

90

100

Time in Days

0 30 60 90 120 150 180 210

Days ff Maj Amp (95% CI) At Risk

30 99.1% (97.9%,100%) 225

180 98.6% (97.1%,100%) 163

210 98.0% (96.0%,100%) 112

Days ff CD-TLR (95% CI) At Risk

30 100% (100%,100%) 225

180 92.0% (88.3%,95.8%) 152

210 88.7% (84.1%,93.3%) 105

6m K-M Freedom from CD-TLR: 92.0%

Page 16: Repairing BTK dissection: Results from the TOBA II BTK

95.7%

Fre

edom

fro

m A

mputa

tion-f

ree S

urv

ival (%

)

0

10

20

30

40

50

60

70

80

90

100

Time in Days

0 30 60 90 120 150 180 210

All-Cause Mortality, Amputation-Free Survival

Days AFS* (95% CI) At Risk

30 98.7% (97.2%,100%) 225

180 95.7% (93.0%,98.5%) 173

210 92.5% (88.6%,96.3%) 122

Zero amputations in RC3 patients

97.0%

Surv

ival (%

)

0

10

20

30

40

50

60

70

80

90

100

Time in Days

0 30 60 90 120 150 180 210

(ITT population)

6m K-M Amputation-Free Survival: 95.7%6m K-M Survival: 97.0%

Days Survival (95% CI) At Risk

30 99.6% (98.7%,100%) 225

180 97.0% (94.7%, 99.4%) 173

210 94.3% (90.9%,97.8%) 122

Page 17: Repairing BTK dissection: Results from the TOBA II BTK

Improvement in Wound Status

Wound Status6 Month(n=122)

Wound has healed 57.4%

Wound is improving 16.4%

Wound is unchanged 4.9%

Wound is worsening 2.5%

Unable to assess 18.9%

73.8% of wounds were healed or improving

at 6 months

(Site reported; ITT population)

Page 18: Repairing BTK dissection: Results from the TOBA II BTK

74.0% of CLI

patients

improved to

RC ≤3

45.3% of all

patients

improved ≥3

classes

(ITT population)Significant Improvement in Rutherford Class

0,1 2 3 4 5 6

Baseline Rutherford Class (n=199)

% o

f Pa

tien

ts

60%

50%

40%

30%

20%

10%

0%

16.3%

33.5%

50.2%

16.3%

33.5%

50.2%

7.0%

16.1%

55.8%

3.0%

17.1%

1.0%

6-Month Rutherford Class (n=199)

p<0.0001*

*Wilcoxon Signed Rank test.

Page 19: Repairing BTK dissection: Results from the TOBA II BTK

*Wilcoxon Signed Rank test.

Hemodynamic and QoL Improvement

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

TBI

Toe Brachial

Index

p<0.0001*

Baseline

6 Months

EQ-5D-3L Score

Limitations in Mobility Limitations in Pain

p<0.0001*

0

10

20

30

40

50

60

70

80

None Some Extreme None Some Extreme

(ITT population)

Page 20: Repairing BTK dissection: Results from the TOBA II BTK

• Unique trial: first BTK IDE to enroll 100% dissected vessels

• Successfully met all primary and secondary endpoints

• Demonstrated that the Tack implant repaired 100% of BTK dissections:

– 87.3% 6m K-M target lesion patency

– 92.0% 6m K-M freedom from CD-TLR

– 73.8% of wounds healed or improved at 6 months

– 74.0% of CLI patients decreased to RC ≤3 at 6 months

– 95.7% 6m K-M amputation-free survival

• Preserves future treatment options

Tack: A New Therapy for BTK Dissection Repair

Page 21: Repairing BTK dissection: Results from the TOBA II BTK

Repairing BTK dissection: Results from the TOBA II BTK pivotal study

George Adams, MD, MHS, MBA, FACC, FSCAI

North Carolina Heart and Vascular, Rex Hospital

Raleigh, NC