Upload
others
View
5
Download
0
Embed Size (px)
Citation preview
Future trials with drug eluting technologies
G. Torsello
Münster, Germany
Disclosure
Speaker name:
......................G. Torsello...........................................................
I have the following potential conflicts of interest to report:
X Consulting (Medtronic, Cook, Cordis, Boston, Gore)
Employment in industry
Stockholder of a healthcare company
Owner of a healthcare company
Other(s)
I do not have any potential conflict of interest
COMPARE I*Multicenter, RCT 1:1(Ranger : In.Pact)
N = 414Pilot N=150 24M complete.N=414 12M follow up complete
RANGER SFA (FIH)Multicenter, RCT 2:1(Ranger : PTA)
N = 105 36M follow up complete
Ranger SFA Registry* Multicenter, registry N = 172 24M follow up complete
Ranger II Global PivotalMulticenter, RCT 3:1(Ranger : PTA)
N = 376 12M follow up complete
Ranger DCB China Multicenter, single-arm N = 123 Enrolling
RANGER-BTK* Single center, single-arm N = 30 12M follow up complete
DCB vs PTA in CLI and Crural Arteries*
Single center, RCT 1:1(Ranger : PTA)
N = 70 Enrolling
DCB Venoplasty in AV Fistula Stenosis (DeVA)*
Multicenter, RCT 1:1(Ranger : PTA)
N = 186Enrollment stop and follow up
BSC Peripheral DCB Clinical Program
*These investigator-sponsored studies are supported by grant funding from Boston Scientific. Boston Scientific is not responsible for the collection, analysis or reporting of these studies which remain the sole responsibility of the investigators. Information for the use in countries with applicable product registrations.Ranger DCB is an investigational device and not available for sale in the US.
Head to Head
DCB trials rationale
RANGER II SFA Global Pivotal
Multicenter, RCT 3:1 (Ranger : PTA)
COMPARE IMulticenter, RCT 1:1
(Ranger : In.Pact)
RandomizationProportionate – PTA well described → 3:1
?equipoise → 1:1
ComparatorPTA standard of care
at time in US
Market leading comparative device
EMEA
Data generation Increase datapoints for DCB
Head to head Low risk strategy High risk strategy
COMPARE I*Multicenter, RCT 1:1(Ranger : In.Pact)
N = 414Pilot N=150 24M complete.N=414 Enrollment complete
RANGER SFA (FIH)Multicenter, RCT 2:1(Ranger : PTA)
N = 105 12M follow up complete
Ranger SFA Registry* Multicenter, registry N = 172 12M follow up complete
Ranger II Global PivotalMulticenter, RCT 3:1(Ranger : PTA)
N = 376 12M follow up complete
Ranger DCB China Multicenter, single-arm N = 123 Enrolling
RANGER-BTK*Single center, single-arm
N = 30 6M follow up complete
DCB vs PTA in CLI and Crural Arteries*
Single center, RCT 1:1(Ranger : PTA)
N = 70 Enrolling
DCB Venoplasty in AV Fistula Stenosis
(DeVA)*
Multicenter, RCT 1:1(Ranger : PTA)
N = 186 Enrolling
BSC Peripheral DCB Clinical Program
*These investigator-sponsored studies are supported by grant funding from Boston Scientific. Boston Scientific is not responsible for the collection, analysis or reporting of these studies which remain the sole responsibility of the investigators. Information for the use in countries with applicable product registrations.Ranger DCB is an investigational device and not available for sale in the US.
RANGER BTK CRURAL DCB
Objective A safety and efficacy study to evaluate Ranger drug-eluting balloon for below the
knee angioplasty in patients with critical limb ischemia
Randomized trial comparing drug coated balloon vs plain balloon angioplasty in critical limb ischemia and treatment of long lesions
in crural arteries
PI Marc Sapoval Torbjorn Fransson
Design Prospective, single centre, non-controlled, open-label
Prospective, single centre, randomized
Centres France Sweden
Population 30 patients 70 patients
Primary Efficacy Endpoint
Primary patency (no stenosis >50%) and Late Lumen Loss (LLL) of the Target Lesion measured by Quantitative Vascular Angiography (QVA) at 6 months adjudicated by independent core lab
12 month primary patency
Primary Safety Endpoint
Composite of all death and major amputation at 6 and 12 months
TLR, Event Free Survival, MRA analysis
RANGER DCB BTK Studies
12m FU complete Enrolment completing
BSC PI Drug-Eluting Stent Clinical Program
IMPERIALMulticenter, RCT 2:1(Eluvia : ZilverTMPTXTM)
N = 465 2Y follow up complete
MAJESTICMulticenter, single-arm(Eluvia)
N = 57 3Y follow up complete
EMINENTMulticenter, RCT 2:1(Eluvia : BMS)
N = 750 Enrolling
REGALMulticenter registry(Eluvia)
N = 500 Enrolling
SPORTS*Multicenter, RCT 1:1:1 (Eluvia:DCB:BMS)
N = 222 Enrolling
SAVALMulticenter, RCT 2:1(SAVAL : PTA) & single-arm
N = 201 & N = 100
Enrolling
*These investigator-sponsored studies are supported by grant funding from Boston Scientific. Boston Scientific is not responsible for the collection, analysis or reporting of these studies which remain the sole responsibility of the investigators. Information for the use in countries with applicable product registrations.SAVAL is an investigational device and not available for sale in the US. CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.
Clinical Study Overview: EMINENT
Title A Randomized Trial Comparing the ELUVIA™ Drug-Eluting Stent versus Bare Metal Self-Expanding Nitinol Stents in the Treatment of Superficial Femoral and/or Proximal Popliteal Arteries
Coordinating Principal Investigators
Prof. Yann Goueffic, Nantes, France
Prof. Giovanni Torsello, Münster, Germany
Objective To confirm superior effectiveness of the ELUVIA Drug-Eluting Vascular Stent System (ELUVIA Stent) for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions up to 140 mm in length when compared against bare metal stents, and collect additional data including health economics data.
Study Design Prospective, multi-centre, single-blind, superiority trial (RCT)Randomized 2:1 (Eluvia : Self Expanding BMS)*Powered for 10% Primary Patency superiority*
Subjects 750 subjects to receive treatment Total lesion length (or series of lesions) ≥ 30 mm and ≤140 mmRutherford 2-4Stenosis ≥70% by visual angiographic assessment
Enrolling
EMINENT Clinical Study
CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.
Clinical Study Overview: EMINENT
Investigational Centers
Up to 75 study centres in up to 10 EU countries:• Germany, Austria, Belgium, United Kingdom, France, Italy, Spain, Switzerland,
The Netherlands (potentially Central Eastern Europe)
PrimaryEffectiveness Endpoint
Primary patency • Freedom from more than 50% stenosis based on PSVR ≤ 2.4• Assessed by duplex ultrasound (DUS) at 12 months post-procedure and
adjudicated by an independent core laboratory
Secondary Endpoint
Health Economics• Walking Improvement at 12 months assessed by change in Six Minute Hall Walk
(6MHW) from baseline
• Walking Improvement and Quality of Life Improvement assessed at 1 month, 6 months, 12 months, 24 months and 36 months assessed by change in Walking Impairment Questionnaire (WIQ) and EQ-5D™ from baseline
• Changes in healthcare utilization over time and associated health care costs
Follow-Up Index, 1m, 6m, 1-year (primary endpoint), 2-year, and 3-year
EMINENT Clinical Study
CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.
Soga et. al., J Atheroscler Thromb, 2019
• 12-month angiography
performed for 66 patients
from 4 Japanese institutions
enrolled in the IMPERIAL trial
• Late lumen loss was
significantly less for the
Eluvia group
Late Lumen Loss
BSC PI Drug-Eluting Stent Clinical Program
IMPERIALMulticenter, RCT 2:1(Eluvia : ZilverTMPTXTM)
N = 465 2Y follow up complete
MAJESTICMulticenter, single-arm(Eluvia)
N = 57 3Y follow up complete
EMINENTMulticenter, RCT 2:1(Eluvia : BMS)
N = 750 Enrolling
REGALMulticenter registry(Eluvia)
N = 500 Enrolling
SPORTS*Multicenter, RCT 1:1:1 (Eluvia:DCB:BMS)
N = 222 Enrolling
SAVALMulticenter, RCT 2:1(SAVAL : PTA) & single-arm
N = 201 & N = 100
Enrolling
*These investigator-sponsored studies are supported by grant funding from Boston Scientific. Boston Scientific is not responsible for the collection, analysis or reporting of these studies which remain the sole responsibility of the investigators. Information for the use in countries with applicable product registrations.SAVAL is an investigational device and not available for sale in the US. CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.
Head to Head
BSC PI Drug-Eluting Stent Clinical Program
IMPERIALMulticenter, RCT 2:1(Eluvia : ZilverTMPTXTM)
N = 465 2Y follow up complete
MAJESTICMulticenter, single-arm(Eluvia)
N = 57 3Y follow up complete
EMINENTMulticenter, RCT 2:1(Eluvia : BMS)
N = 750 Enrolling
REGALMulticenter registry(Eluvia)
N = 500 Enrolling
SPORTS*Multicenter, RCT 1:1:1 (Eluvia:DCB:BMS)
N = 222 Enrolling
SAVALMulticenter, RCT 2:1(SAVAL : PTA) & single-arm
N = 201 & N = 100
Enrolling
*These investigator-sponsored studies are supported by grant funding from Boston Scientific. Boston Scientific is not responsible for the collection, analysis or reporting of these studies which remain the sole responsibility of the investigators. Information for the use in countries with applicable product registrations.SAVAL is an investigational device and not available for sale in the US. CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.
Clinical Study Overview: REGAL
Title A Real World Evaluation of ELUVIA™ Drug-Eluting stent in All-Comers Superficial Femoral Artery and Proximal Popliteal Artery Disease
Primary Investigator Prof Carlo Setacci, Siena, Italy
Objective Collect additional data including health economics data to support the use of the ELUVIA Drug-Eluting Vascular Stent System for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions
Study Design Prospective, multi-centre, single-arm, open-label registry
Subjects 500 subjects at up to 30 study centres in up to 10 EU countries• Stenotic, restenotic or (re)occluded lesion(s) in the femoro-popliteal
arteries suitable for endovascular treatment
PrimaryEffectiveness Endpoint
Primary patency • Freedom from more than 50% stenosis based on PSVR ≤ 2.4• Assessed by duplex ultrasound (DUS) at 12 months post-procedure
Primary Safety Endpoint
Major Adverse Event (MAE) rate defined as:• All cause death through 1 month• Target limb major amputation through 12M• Target lesion revascularization (TLR) through 12M
Follow-Up Index, 1m, 6m, 1-year (primary endpoint), and 2-years (standard of care)
REGAL Clinical StudyEnrolling
CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.
BSC PI Drug-Eluting Stent Clinical Program
IMPERIALMulticenter, RCT 2:1(Eluvia : ZilverTMPTXTM)
N = 465 2Y follow up complete
MAJESTICMulticenter, single-arm(Eluvia)
N = 57 3Y follow up complete
EMINENTMulticenter, RCT 2:1(Eluvia : BMS)
N = 750 Enrolling
REGALMulticenter registry(Eluvia)
N = 500 Enrolling
SPORTS*Multicenter, RCT 1:1:1 (Eluvia:DCB:BMS)
N = 222 Enrolling
SAVALMulticenter, RCT 2:1(SAVAL : PTA) & single-arm
N = 201 & N = 100
Enrolling
*These investigator-sponsored studies are supported by grant funding from Boston Scientific. Boston Scientific is not responsible for the collection, analysis or reporting of these studies which remain the sole responsibility of the investigators. Information for the use in countries with applicable product registrations.SAVAL is an investigational device and not available for sale in the US. CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.
Clinical Study Overview: SPORTS
TitleSequent Please Drug Coated Balloons Versus Primary Stent Application in Long SFA Lesions
Primary Investigator/ Sponsor
Gunnar Tepe, MD - RoMed Klinikum Rosenheim, Germany
InnoRa GmbH
ObjectiveCompare angiographic and clinical outcome of PTA with a paclitaxel coated balloon versus nitinol stent (paclitaxel-eluting or bare metal) with regard to restenosis development
Study DesignProspective, multicenter, RCT 1:1:1 (Eluvia DES: SeQuent Please PCB : Nitinol stent)
Subjects
Up to 222 patients
• Rutherford stage 2-4
• Occlusion or stenosis ≥70% of diameter and ≥13 cm length in the SFA and/ or PI-segment of popliteal artery
Investigational Centers
Up to 11 centers in Germany
Primary EndpointPercent diameter stenosis at 1 year post intervention in successfully treated patients by quantitative angiography
These investigator-sponsored studies are supported by grant funding from Boston Scientific. Boston Scientific is not responsible for the collection, analysis or reporting of these studies which remain the sole responsibility of the investigators. Information for the use in countries with applicable product registrations. CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.
SPORTSEnrolling
BSC PI Drug-Eluting Stent Clinical Program
IMPERIALMulticenter, RCT 2:1(Eluvia : ZilverTMPTXTM)
N = 465 2Y follow up complete
MAJESTICMulticenter, single-arm(Eluvia)
N = 57 3Y follow up complete
EMINENTMulticenter, RCT 2:1(Eluvia : BMS)
N = 750 Enrolling
REGALMulticenter registry(Eluvia)
N = 500 Enrolling
SPORTS*Multicenter, RCT 1:1:1 (Eluvia:DCB:BMS)
N = 222 Enrolling
SAVALMulticenter, RCT 2:1(SAVAL : PTA) & single-arm
N = 201 & N = 100
Enrolling
*These investigator-sponsored studies are supported by grant funding from Boston Scientific. Boston Scientific is not responsible for the collection, analysis or reporting of these studies which remain the sole responsibility of the investigators. Information for the use in countries with applicable product registrations.SAVAL is an investigational device and not available for sale in the US. CAUTION: The law restricts these devices to sale by or on the order of a physician. Rx Only.
• Global Pivotal Trial of the SAVAL Drug-Eluting Vascular Stent System
• Differentiated technology selected for Expedited Access Pathway (EAP) designation by FDA+
• First Ever EAP in the Peripheral Branch of FDA
• Enrollment began Aug 2018
The SAVALTM Pivotal Trial
+FDA’s Expedited Access Pathway (EAP) program is intended for
breakthrough medical devices that demonstrate the potential to address
unmet medical needs for life threatening or irreversibly debilitating diseases.
CAUTION: Investigational device and not available for sale in the U.S.
• Dual Layer System (same as Eluvia)
• Primer Layer (PBMA): Promotes Adhesion of Active Layer to Stent
• Active Layer (PTx, PVDF-HFP)– Controls Release of Paclitaxel
• Dose: 0.236 µg PTx/mm2 stent surface area
SAVALTM Coating Design
SAVAL is an investigational device and not available for sale in the US. Boston Scientific Data on File.
Stent
PBMA Primer Layer
Paclitaxel/PVDF-HFP Active Layer
Title A Randomized Trial comparing the Drug-Eluting Stent (DES) Below the Knee (BTK) Vascular Stent System vs Percutaneous Transluminal Angioplasty (PTA) Treating Infrapopliteal Lesions in Subjects With Critical Limb Ischemia
Principal Investigators
Global: Jihad Mustapha, MD, FACC FSCA
US: Patrick J. Geraghty, MD, FACS, RPVIEU: Hans van Overhagen, MD, PhD, EBIRJapan: Masato Nakamura, MD, PhD
Objectives Demonstrate a superior patency rate and acceptable safety in below-the-kneearteries with lesions treated with the SAVAL Stent vs PTA.Secondary: To collect additional information on limb salvage and overall quality of life in this patient population.
Study Design Phase A- RCT Phase B- single arm
Global, prospective, multicenter, 2:1 randomized (SAVAL vs PTA)
Stent size 3.5 mm x 80 mm
Sequential, single-arm study to collect ongoing safety and effectiveness dataStent sizes: Diameters 3-4 mm; Lengths 30, 80, 120 mm
Patients ~201 subjects (2:1 randomization) ~100 subjects
• up to 50 study centers in the US, Europe, and Japan
Follow-UpOffice visits at 1, 3, 6, 12, 24, and 36 months post procedureTelephone follow-up at 18 and 30 months post procedure
SAVAL Clinical StudyEnrolling
SAVAL is an investigational device and not available for sale in the US. Boston Scientific Data on File.
• Data generation is expensive, time consuming and not without risk but ultimately underpins therapy area for advancement of patient outcomes.
• Head to Head trials answer relevant clinical questions :
Efficacy (TLR reduction) and subsequent health economics.
Long term safety
• Level 1 RCT data sets a bar for new entrants :
CE approval
EU MDR and global regulatory oversight
Evidence-based adoption
Conclusions
Future trials with drug eluting technologies
G. Torsello
Münster, Germany