prelude-btk study

PRELUDE-BTK STUDY

PRospective Study for the TrEatment of Atherosclerotic Lesions in the Infrapopliteal Arteries Using the

Serranator DevicE

PRELUDE BTK

Balloon Diameter

(mm)

Balloon Length (mm)

Guidewire Compatibility

Sheath Size (F)

Number of Strips

2.5, 3.0, 3.5

40

0.014" 6 380

120

Catheter Length: 150cm

Serration Technology provides effective and stable lumen gain

• Effective: achieve nominal lumen diameter• Stable: minimize dissection, maintain lumen gain*

Indication for Use:

The Serranator® PTA Serration Balloon Catheter is intended for dilatation of lesions in infrapopliteal arteries. Not for use in the coronary or neuro-vasculature.

* Freedom from CD-TLR 97.7% @ 6 months

PRELUDE BTK

Mechanism of Action: Serration Angioplasty

PRELUDE BTK

for Effective and Stable Lumen Gain

Serrating Elements use “Point Force”

• Applies 1,000x the force compared to POBA

• Enables low pressure inflation (6 ATM*)

3 Linear Serrated Strips (120˚ apart)

• Symmetrical Stress Relief ensures equal pressure across treatment segment

• Opens resistant lesions

*PRELUDE-BTK Study: 6ATM Average Maximum Pressure

PRELUDE-BTK Study Completed: (n=49 Subjects) (manuscript in progress)

PRELUDE BTK

Inclusion Exclusion

Rutherford 3, 4 or 5 (< 20% of subjects enrolled with R3) Rutherford 1, 2, or 6

RVD between 2.5 – 3.5mm Previously implanted stent

Up to 2 lesions within infrapopliteal tibial arteries CTO > 12 cm

Stenosis > 70% Evidence of acute thrombus

Lesion(s) length < 12 cm Atherectomy

De-novo, or non-stented restenotic lesions 2 lesions in 1 vessel, only 1 qualifies

Objective

Study Design

Core Lab Assessment

Follow-up

Assess safety and efficacy of the Serranator® PTA Serration Balloon Catheter in subjects with atherosclerotic peripheral artery disease of the infrapopliteal arteries.

Single Arm, Prospective Multi-center Study with atherosclerotic lesions in the

infrapopliteal arteries and/or Critical Limb Ischemia (CLI).

Corelab assessments Angiogram, OCT, IVUS

Co-PIs

30 day & 6 month100% data monitoring by local CRO

Drs. Andrew Holden & Michael Lichtenberg

PRELUDE BTK – Primary Objectives and Endpoints

Primary Objective:

To evaluate the performance of the Serranator® PTA Serration Balloon Catheter during the endovascular treatment of critical infrapopliteal artery lesions.

Primary Endpoints:

Safety: Composite of Major Adverse Limb Events (MALE) and Peri-procedural Death (POD), assessed at 30 days post procedure. MALE plus POD is defined as a composite of all cause death, thrombolysis/thrombectomy at the target lesion, open surgical revision or bypass, and major (above ankle) target limb amputation at 30 days post procedure. Safety will be evaluated on a per subject basis.

Efficacy: Procedural efficacy will be assessed by the rate of device success defined as the achievement of successful insertion, balloon inflation and deflation, and removal of the study device(s) with a final diameter stenosis of <50% by visual assessment at the intended target site using only the Serranator device. Device success will be evaluated on a per lesion basis.

Secondary Objective:

The secondary objective of this study is an assessment of the feasibility of using Optical Coherence Tomography (OCT) or Intravascular Ultrasound (IVUS) pre and/or post treatment in a sub-set of up to 10 subjects, as tools to evaluate lesion characteristics, the adequacy of lumen expansion/patency and the presence of linear serrations across the lesion after use of the Serranator.

PRELUDE BTK

Subject Baseline Demographics

PRELUDE BTK

Demographic n

Male 30/46 (65.2%)

Age Avg. (range) 78 (61-94)

Diabetes 25/45 (55.6%)

Current/Former Smoker 27/45 (60%)

Hypertension 44/46 (95.7%)

High Cholesterol 40/46 (87.0%)

Coronary Artery Disease 16/46 (34.8%)

Prelude BTK Lesion Status (n = 49 Subjects)

PRELUDE BTK

53 Lesions

were

Analyzable

2 Lesions had

Incomplete

Images

55 LESIONS

REVIEWED BY

CORE LAB

5 LESIONS

UNABLE TO

CROSS

PRELUDE-BTK: 60 Total Lesions

Primary Endpoint Analysis

Free from Primary Safety Event at 30 Days 44/46 (95.7%)

Primary Safety Events at 30 Days

Death < Day 30 (not related to device)

Major Amputation < Day 30 (not related to device)

Major Re-intervention < Day 30

1

1

0

PRELUDE BTK

Composite of Major Adverse Limb Events (MALE) and Peri-procedural Death (POD), assessed at 30 days post procedure. MALE plus POD is defined as a composite of all cause death, thrombolysis/thrombectomy at the target lesion, open surgical revision or bypass, and major (above ankle) target limb amputation at 30 days post procedure. Safety was evaluated on a per subject basis.

Procedural efficacy was assessed by the rate of device success defined as the achievement of successful insertion, balloon inflation and deflation, and removal of the study device(s) with a final diameter stenosis of <50% by visual assessment at the intended target site using only the Serranator device. Device success was evaluated on a per lesion basis.

Treatment success on attempted lesions 1 55/60 (91.7%)

Treatment success on treated lesions 2 55/55 (100.0%)

Safety

Efficacy

1 For attempted lesions, success based on use of Serranator to achieve less than 50% residual stenosis by on the site visual assessment.2 Serranator treated lesions, success based on less than 50% residual stenosis by the site visual assessment.

Acute Clinical Results – Core Lab Analysis

Lesions Treated n = 53 (SynvaCor analysis)

RVD* 2.5 ± .7mm

MLD* .5 ± 0.5mm

Lesion Length* 47.8 ± 37.4mm

Pre-Diameter Stenosis* 81.3 ± 17.2%

Residual Stenosis* 21.8 ± 12.7%

# CTO 15/53 = 28.3%

Bailout Stent Rate 1/53 = 1.9%*

Dissections by Grade 0: 38/53 = 71.7%A/B: 13/53 = 24.5%C/D: 1/53 = 1.9%Unk: 1/53 = 1.9%

Degree of Calcification None/Mild: 37/53 = 69.8%Moderate/Severe: 14/53 = 26.4%Unk: 2/53 = 3.8%

Average Maximum ATM Used 6

OCT/IVUS (by CRF core lab) Subset (n=10 lesions) showed positive Serration Effect (7 IVUS/3OCT)

PRELUDE BTK

*55 lesions treated total, only 53 analyzable by core lab. Of the 2 unanalyzable lesions, 1 had a stent placed

Pre and Post Treatment Diameter Stenosis (n=53) per lesion

21,80%

0,00%

10,00%

20,00%

30,00%

40,00%

50,00%

60,00%

70,00%

80,00%

90,00%

Core Lab Adjudicated Data

Pre Treatment Stenosis Post Treatment Stenosis

PRELUDE BTK

Lesion Pre-Dilatation by RVD

53%38%

9%

Lesions by RVD (n=53)

<2.5 2.5-3.5 >3.5

PRELUDE BTK

58%

36%

85%80%

42%

64%

15%20%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

All (n=53) <2.5mm (n=28)* 2.5-3.5 (n=20) >3.5mm (n=5)

No Pre-Dil Pre-Dil

MAX: RVD 4.4mmMIN: RVD 1.2mm

*treated with Xience stent

Technical Safety Demonstrated

53%38%

9% Lesions by RVD** (n=53)

<2.5 2.5-3.5 >3.5

PRELUDE BTK

• 32% of lesions below 2.5mm RVD were CTOs• Flow-Limiting Dissection (n=1) occurred in artery with RVD 1.78mm*• 62% of Lesions were outside study RVDs by Core Lab Assessment yet

the average residual stenosis for these lesions was 21.8%

81% 81% 82%85%

22% 20% 22%

32%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

All (n=53) <2.5mm (n=28)* 2.5-3.5 (n=20) >3.5mm (n=5)

Pre-Serranator Post-Serranator

MAX: RVD 4.4mmMIN: RVD 1.2mm

*treated with Xience stent**All diameter measurements as per Core Lab

Subject # 01-002 – TP Trunk

PRELUDE BTK

Pre-Procedure Inflation Post-Inflation

2.5 x 80 SerranatorMax ATM: 10

RVD: 2.59Stenosis: 87%Lesion Length: 48.65 mm Calcification: Moderate

RVD: 2.59Residual Stenosis: 28%Dissection: B

Performed By: Prof. Andrew Holden

Subject # 03-001 – TP Trunk

PRELUDE BTK

Pre-Procedure Inflation Post-Inflation

RVD: 3.72Stenosis: 100%Lesion Length: 29.67mm Calcification: No

RVD: 3.01Residual Stenosis: 22%Dissection: No

3.0 X 40 SerranatorMax ATM: 6

Performed By: Dr. Marianne Brodmann

Subject # 03-008 - TP Trunk

PRELUDE BTK

Pre-Procedure

RVD: 3.07Stenosis: 73%Lesion Length: 7.43mm Calcification: None

Inflation Post-Inflation

Residual Stenosis: 18%Dissection: No


Performed By: Dr. Marianne Brodmann

Final Clinical Findings: IVUS & OCT

PRELUDE BTK

Study Objective: Evaluate lesion characteristics, adequacy of lumen expansion/patency, presence of linear serrations across the lesion, and post-procedure dissections using IVUS and OCT imaging

Study Conclusion:*

• 100% of lesions had serration effect (n=10)• Compared with POBA the Serranator made multiple

very distinct serrations throughout the entire treatment segment allowing for an increase in lumen area.

• No adventitial dissections or hematomas were observed

• Serration effects were observed in both non-calcified fibrotic plaque and calcified plaque.

Akiko Maehara, MD

* Intravascular Imaging Summary Report for Prospective Study for the Treatment of Atherosclerotic Lesions in the Infrapopliteal Arteries Using the Serranator Device: PRELUDE BTK (Below the Knee) Study, 09.25.20 A. Maehara, CRF

Pre Serranator Post Serranator

Subject 01-002 OCT Pre and Post Showing Serrations

PRELUDE BTK

Pre Serranator

Post Serranator

Pre Serranator


Performed by Prof. Andrew Holden (PI PRELUDE-BTK Study)

NOT CALIBRATED

Pre-Intervention

Post-Serranator

Pre-InterventionPost-Serranator A B C D

Aꞌ Bꞌ Cꞌ Dꞌ

ABC

D

Aꞌ

Bꞌ

Cꞌ

Dꞌ

IVUS Imaging of Posterior Tibial Artery

PRELUDE BTK

Performed by Dr. Klaus Hertting (Investigator PRELUDE-BTK Study)

Pre-intervention imaging showed diffuse circumferential superficial calcification (A-D)

Post-Serranator angiogram showed slits (yellow arrows) in the superficial calcium enabling enlargement of lumen without any dissection (A’-D’)

Dr. Akiko Maehara, Director, Intravascular Imaging

Core Laboratory and MRI Core Laboratory, CRF

Freedom From Clinically-Driven TLR at 30 days and 6 months

Freedom from Clinically-Driven TLR Endpoint Analyzed as a

Binary Endpoint Through 6 Months

Subjects (N=46)

Visit Response Rate

30 Days 46 / 46 (100.0%)

6 Months 42 / 43 (97.7%)

PRELUDE BTK

97.7% Freedom

from CD-TLR at 6 months

Freedom From TOTAL TVR/TLR at 30 days and 6 months

Freedom from Total TVR Endpoint Analyzed as a Binary

Endpoint Through 6 Months

Subjects (N=46)

Visit Response Rate

30 Days 46 / 46 (100.0%)

6 Months 40 / 43 (93.0%)

PRELUDE BTK

Freedom from Total TLR Endpoint Analyzed as a Binary

Endpoint Through 6 Months Subjects (N=46)

Visit Response Rate 30 Days 46 / 46 (100.0%)

6 Months 41 / 43 (95.3%)

95.3% Freedom

from Total TLR at 6 months

6 Month Rutherford Results

PRELUDE BTK

0%

10%

20%

30%

40%

50%

60%

70%

0 1 2 3 4 5 6

Rutherford Clinical Category Improvement

Baseline 6 Months

n=46 n=43*

* 2 deaths and 1 withdrew

70% Improvement in 1 or more

RCC at 6 months

Total Freedom From Minor/Major Amputation at 30 days and 6 months

Freedom from Target Limb Minor Amputation Endpoint

Analyzed as a Binary Endpoint Through 6 Months

Subjects (N=46)

Visit Response Rate

30 Days 46 / 46 (100.0%)

6 Months 42 / 43 (97.7%)

PRELUDE BTK

Freedom from Target Limb Major Amputation Endpoint

Analyzed as a Binary Endpoint Through 6 MonthsSubjects (N=46)

Visit Response Rate 30 Days 45 / 46 (97.8%)

6 Months 42 / 43 (97.7%)

97.7%Freedom

from target limb

amputation at 6 months

PRELUDE BTK Conclusions

• The Serranator is safe and effective in treating infrapopliteal artery lesions

• Acute results demonstrated a low residual stenosis (21.8%), low bailout stent rate (1.9%), and used low ATM pressure (6 ATM Avg Max) to achieve results

• Low reintervention rate at 6-months CD-TLR (97.7%)

• All lesions imaged with OCT and IVUS showed serration effect (n=10)

• No device related SAEs

PRELUDE BTK

PRELUDE-BTK STUDY

PRospective Study for the TrEatment of Atherosclerotic Lesions in the Infrapopliteal Arteries Using the

Serranator DevicE

PRELUDE BTK

prelude-btk study

Documents