View
220
Download
0
Category
Preview:
Citation preview
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
Recommended