EffPac - Trial: Study design & Status report

Ulf Teichgräber, MD, MBA

Disclosure of conflict of interest

Speaker name: Ulf Teichgräber, MD, MBA

Potential conflicts of interest related to the presentation:

o Research grant: iVascular, Endoscout

Potential conflicts of interest not related to the presentation:

o Consulting Fees, Honoraria, Research Grants, Advisory Boards:

ab medica, Abbott Vascular, B.Braun Melsungen, Boston

Scientific, Celonova, C.R. Bard, COOK, Endoscout, GE

Healthcare, iVascular, Kimal, Maquet, Medtronic, Philips

Healthcare, Siemens Heathcare, Spectranetics, W.L.Gore

o Master research agreements with Siemens Healthcare, GE

Healthcare

Various Drug Concentrations and Excipients

Schnorr Expert Rev Med. Devices (10(1) 105-114 (2013)

DCB Drug Dose

(µg/mm2) Excipient

LutonixTM* Bard Paclitaxel 2 Polysorbate & Sorbitol

InPactTM* Medtronic Paclitaxel 3 Urea

FreewayTM* Eurocor Paclitaxel 3 Shellac

Passeo 18 LuxTM* Biotronik Paclitaxel 3 N-butyryl-tri-n-

hexylcitrate

Advance PTXTM* Cook Paclitaxel 3 None

RangerTM* Boston Scienfitic Paclitaxel 2 Citrate Ester

LegflowTM* Cardionovum Paclitaxel 3 Shellac

ElutaxTM* Aachen Resonance Paclitaxel 2 None

Dosage of uniform diameter

nanodrops by direct

ultrasonic deposition

Control over drug morphology

SEM: magnify: x250

SEM: magnify: x 1000

luminor35

Paclitaxel coated balloon

• Ultrathin multilayer coating:

- DURABILITY

- Minimum drug loss

• Homogeneous distribution of drug

- Accurate dosage

MICROCRISTALLINE paclitaxel

TRANSFERTECH

MICROCRISTALLINE paclitaxel

• Efficacy FAST drug TRANSFER

• Safety MINIMUM drug LOSS

Different Coating Technology

Paclitaxel coated balloon

luminor 35 Paclitaxel coated balloon

Balloon lengths 20 mm – 150 mm

Architecture OTW & double lumen

Balloon diameters 5 mm – 7 mm

Catheter lengths 80 cm + 140 mm

Pressure

Nominal 6 / 7 atm RBP 16 atm AVP 23 atm

Introducer

Ø [mm]: 5.0 5F Ø [mm]: 6.0 – 7.0 6F

Deflation times 5 s maximum

Formulation Paclitaxel (3µg/mm2) + lypophillic carrier

LUMINOR 35 Restrospective Registry Patient characteristics (n = 18)

Enrolment Status Cardiovascular Risk Factors

Male 13 Myocardial Infarction 0

Female 5 Hyperlipidemia 9

Age (mean) 69 ± 11 SD Hypertension 14

Smoking* 8**

Diabetes 6

Heart Failure 2

CAD 5

CVD 1

Renal Insufficiency 5

* three patients unknown

** two patients previous smoker

LUMINOR 35 Restrospective Registry Lesion characteristics (n = 18)

Target lesion location *

SFA 11

SFA and Apop 7

* site reported data

Calcification of Target Vessel *

little 3 (16%)

moderate 11 (61%)

heavy 3 (16 %)

NA 2 (7 %)

LUMINOR 35 Restrospective Registry Procedural characteristics (n = 18)

Lesion length *

[cm] (mean) Dilatation

Degree of Stenosis *

[%] (mean)

13,8 ± 8,7 SD Pre-dilatation 3 Severity 88 ± 12 SD

Post-dilatation 1 Pre-Procedure 88 ± 12 SD

LUMINOR 35 *** 40 ± 12 SD

Final *** 19 ± 12 SD

* site reported data

** three patients dissection occured

*** additional treatment with Stent

LUMINOR 35 Restrospective Registry Clinical Outcome (n = 18)

until 6 MFU

Efficacy: Freedom of TLR 17 94,4 %

Safety: Freedom of TVR 15 83,3 %

Safety: Freedom of major index limb amputation

18 100 %

EFFPac-trail

Multicenter Randomized Controlled Trial to Assess the

Effectiveness of Paclitaxel-coated Luminor® Balloon

Catheter versus Uncoated Balloon Catheter in the

Superficial Femoral and Popliteal Arteries to Prevent

Vessel Restenosis or Reocclusion

EFFPac-trial

Design:

Investigator initiated, prospective, multi-centre trial

and 2 arms randomised study

Sponsor: University of Jena, Germany

Representative of the sponsor:

Prof. Dr. Ulf Teichgräber, Jena University Hospital

EFFPac-trail

CoreLab

Dr. Ulrich Beschorner, coreLab Bad Krozingen GmbH,

Germany

Data Management and Safety Board (DMSB)

Dr. Michael Werk, Martin Luther Krankenhaus, Berlin, Germany

Dr. Vicenc Riambau, Hospital Clinic de Barcelona, Spain

Prof. Dr. Wienke, University Halle-Wittenberg, Germany

Monitoring and SAE Reporting (VascuScience GmbH) Dr. Kerstin Heitkamp and Lars Mahler, Leipzig, Germany

Project Management

Cornelia Eichorn, Nicole Brillinger, Dr. Andrea Rößler, University

Jena, Germany

Producer of the Investigational Product Life Vascular Devices Biotch, S.L., Barcelona, Spain

EFFPac-trail 11 Participating Sites

01 Jena PD Dr. R. Aschenbach, University Hospital

02 Leipzig Prof. Dr. Dierk Scheinert, University Hospital

03 Bad Krozingen Prof. Dr. Thomas Zeller, Heart Center

04 Hamburg Dr. S. Sixt, Angiologikum

05 München PD Dr. M. Treitl, University Hospital

06 Berlin Prof. Dr. K. Brechtel, „Ihre Radiologen“

07 Sonnebrg Dr. M. Thieme, Medinos Clinic

08 Karlsbad Prof. Dr. E. Blessing, SRH-Clinic

09 Heidelberg Dr. B. Vogel, University Heidelberg

10 Arnsberg Dr. M. Lichtenberg, Clinic Arnsberg

11 Kusel Dr. P. von Flotow, Westpfalz Clinic

Objective

Safety and efficacy of the Luminor® paclitaxel

drug‐eluting balloon in inhibiting restenosis and in

ensuring long‐term patency

Device

Luminor® 35 Paclitaxel Eluting Peripheral Balloon

Dilatation Catheter marked in European Union since

2013. (iVascular, S.L.U., Barcelona, Spain)

EFFPac-trial Power Calculation

Assumptions for sample size calculation:

Average lumen* loss after 6 months in

POBA group: 0.5mm (SD 1.1mm)

DEB group: 1.0mm (SD 1.1mm)

Power 80%, alpha 0.05, drop-out (primary endpoint)

10%, two-sided independent samples t-test

-> “n” to be randomized: n=172

-> “n” to be analyzed: n=154

* Werk et al. 2008

EFFPac-trail Design

Major Inclusion Criteria

• Age > 18 years

• Subject must agree to undergo the 6-month angiographic and

clinical follow-up (at 12 month post-procedure)

• Peripheral vascular disease Rutherford class 2-4

• De novo stenotic/ re- stenotic lesion or occlusive lesions in the

superficial femoral (SFA) and/or popliteal arteries (PA)

• ≥70% diameter stenosis or occlusion

• Target lesion length: ≤15 cm (TASC II A and B)

• ≥one patent infrapopliteal run-off artery to the foot

• If the index lesion is re-stenotic, the prior PTA must have been

>30 days prior to treatment in the current study

EFFPac-trail Design

Major Exclusion Criteria

• Severely calcified target lesions in the SFA/PA resistant to PTA

• Previous intervention or surgery in the target vessel

• Major amputation in the same limb as the target lesion

• Acute myocardial infarction within 30 days before intervention

• Renal insufficiency with a serum creatinine >2.0 mg/dL at baseline

• Platelet count <50 G/l or >600 G/l at baseline

Endpoints

Primary Endpoint:

Late lumen loss (LLL) defined as difference between

the diameters (in mm) at 6 months follow-up minus

post-procedure

Lumen

Late Loss Lumen

Study design

Endpoints (selected)

Secondary Endpoints (selected):

• Patency defined as incidence of restenosis ≥50% (Duplex)

• Freedom from TLR and TVR

• Rutherford stage @ 6M and 12M

• Ankle‐brachial index (ABI) @ 6M and 12M

• Walking distance to baseline @ 6M and 12M

• “Quality of Life” according to the WiQ and EQ5D @ 6M and 12M

Study design

Enrollment

• Endoluminal guide wire passage

• Predilatation with POBA Balloon

and then randomization

Clinical FU:

- Duplex (US), Rutherford stage, ABI

- Walking distance, WIQ, EQ5D

- Adverse Events

- DSA (LLL) ONLY @ 6 months!

172 subjects

to be enrolled

Luminor35

N= 86 POBA

N=86

6 & 12 Month

FUP

6 &12 Month

FUP

Randomisation

1:1

Study design

Study design

Inclusion

Development of recruitment until 2016-01-22

Randomized Patients until 2016-01-22

Total patients randomized: 62 ≈ 1/3 of the required recruitment

2017

6 Months Follow-up results Report of primary end-point: LLL

EffPac - Trial: Study design & Status report

Ulf Teichgräber, MD, MBA