Highlights of Cardiovascular Research Midwest Cardiovascular Research Foundation

Transcription

1 Highlights of Cardiovascular Research Midwest Cardiovascular Research Foundation Nicolas W Shammas, MD, MS, EJD, FACC, FSCAI, FICA Founder and Research Director, Midwest Cardiovascular Research Foundation Interventional Cardiologist, Cardiovascular Medicine, PC Genesis Heart Institute

2 Conflict of Interest Research grants Boston Scientific, Bard Consultant Boston Scientific, Bard Trainer Covidien. RF ablation Boston Scientific. JetStream Atherectomy Stocks, Options, Investments Dr Shammas has no commercial, proprietary or financial interest in any pharmaceutical or device companies or their products and has no intention in doing so in the near future.

3 Midwest Cardiovascular Research Foundation Independent 501 c3 Non profit, Public Charitable Foundation; Established 2002 MCRF s mission is to prolong and improve the quality of life of people in the communities we serve by conducting and disseminating findings of high quality cardiovascular research to the public and health care providers Educated thousands of health care providers Became an investigative site for over 200 national clinical trials Developed over 30 investigator-initiated protocols Published over 350 manuscripts, books, book chapters and abstracts Published 3 textbooks to the public to educate them about heart and blood vessel diseases and general wellness. Became a sponsor for multicenter clinical trials (obtained 2 IDE from the FDA within 1 year to conduct 2 multicenter clinical trials in 39 hospitals in the US). Educated over 40 research students in clinical research Launched the John Hanson Limb Ischemia Council to prevent amputation from PAD

4 Foundation s National Network Educational conferences across the USA and abroad NCVH, TCT, ACC, CVC, CVI, SCAI, MCF, LINC, Industry sponsored programs Research Network: Trial sources UT Southwestern (VA Medical Center). XL PAD NIH DCRI HCRI Clinlogix Direct from Industry (Sponsored studies) IIS (2 IDE trials in 1 year)

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6 Shammas N. J Endovasc Ther Aug;22(4):518-24

7 JetStream ISR Feasibility Study DESIGN: Prospective, feasibility registry at 2 centers, evaluating JetStream XC atherectomy (JS) in treating Femoropopliteal in-stent restenosis (FP ISR) 29 patients (32 limbs) enrolled at 2 clinical sites between October 2012 and August 2014 in the United States 32 limbs crossed intraluminally/js+pta OBJECTIVE: To evaluate efficacy and safety of JS with adjunctive PTA (JS+PTA) and assess stent-device interaction using Angiographic Core Lab adjudication PRINCIPAL INVESTIGATOR Nicolas W Shammas, MD, MS SUBINVESTIGATOR Subhash Banerjee, MD Angiographic Core Laboratory Beth Israel Deaconess Med Ctr Jeffrey Popma, MD Primary Efficacy/Safety endpoints at 1 mo (n=32) Primary Safety endpoint and TLR (n=27 pts; n=29 limbs) Stent Integrity evaluation per core lab (n=24) 1 patient died (2 limbs) 1 patient withdrew (1 limb)

8 Intraprocedural Outcomes/Complications Device Success 75.9 % Residual Stenosis <30%(post adjunctive balloon) 100% Procedural Success (no SAE) 90.6 % Stenting post JS/PTA 9.4% Bail out stenting (2/32) 6.3% Treated Distal Embolization 9.4% New Stent Fracture or No Filter 6.3 % Spider Filter 3.1% Nav-6 Filter 0% 0% Deformities (Core Lab)(n=24) No Abrupt Closure, acute thrombosis, perforation, major bleeding

9 JetStream ISR patient: Baseline, postjs and post adjunctive balloon angioplasty Baseline Post Jetstream Post Angioplasty

10 Freedom from TLR (censored)

11 JET-ISR Trial: Synopsis JET-ISR Registry Objective Evaluate use of Jetstream Atherectomy (JS) and adjunctive balloon angioplasty (JS +PTA) in the treatment of femoropopliteal ISR lesions in subjects with claudication or limb ischemia (Rutherford clinical category (RCC) of 2-4) (lesion length 4 cm). Primary Investigator Study Design Nicolas W Shammas, MD, MS, FACC, FSCAI. Midwest Cardiovascular Research Fd Subhash Banerjee, MD, FACC, FSCAI, VAMC, Dallas, TX A prospective, multicenter, single arm study Comparator arm is historic data from plain old balloon angioplasty derived from a Meta-analysis of the 3 published randomized trials Subjects 140 subjects treated with JS+PTA Investigational Centers Primary Efficacy Endpoint Up to 14 site in the U.S. Target Lesion Revascularization (TLR) at 6 months TLR defined as retreatment of the index lesion (extended 1 cm proximal and distal to the lesion) at 6 months For the primary endpoint, intra-procedural bail out stenting of the index lesion is considered meeting a TLR endpoint. (ITT analysis) Primary Safety Endpoint Major Adverse Events (MAE) at 30 days: Unplanned amputation Total mortality TLR at 30 days (TLR includes bail out stenting)

12 JET-ISR Registry JET-ISR Registry Key Inclusion Criteria Subject presents with a Rutherford Classification of 2-4 and has symptoms of rest limb pain or claudication. Instent restenotic (with restenosis could extend 1 cm prox or distal) Target lesion(s) must be viewed angiographically and have 50% stenosis and is >4 cm The main target vessel reference diameter must be 5 mm and 7 mm One patent distal run-off vessel with <70% disease and with brisk flow is required and not treated during index procedure Intraluminal crossing of the lesion. If this is not certain, IVUS may be used to verify this per operator s discretion Patient has signed approved informed consent. Can be enrolled once in the study Key Exclusion Criteria Diagnosed with chronic renal failure ;creatinine level > 2.5 mg/dl and is not on chronic dialysis. Known allergy to heparin, ASA, or ADP receptor antagonist History of bleeding disorders or platelet count < 80,000 cells/ml. Experiences ongoing cardiac problems (e.g., cardiac arrhythmias, congestive heart failure exacerbation, myocardial infarction, etc.) that, per the investigator, would not make the subject an ideal candidate for study procedures. CVA or TIA within 4 weeks prior to index procedure. Anticipated life span of less than 12 months. Evidence of intracranial or gastrointestinal bleeding within the past 3 months. Severe trauma, fracture, major surgery or biopsy of a parenchymal organ within the past 14 days. Planned surgical intervention or endovascular procedure 30 days after the index procedure. Use of another debulking device, drug eluting balloons, cryoplasty or scoring balloons during the index procedure More than one lesion per target vessel or denovo disease in target vessel Jetstream use within Covered stents Prior Bypass to target limb

13 Trial Update Site Number Principal Investigator Month site Activated ~Enrollment Months completed Subjects Enrolled Avg. / Month 001 Nicolas W Shammas May Subhash Banerjee July Britton Eaves November Nick Petruzzi December Sri Kasula May na 009 Jaafar Golzar February Thomas Shimshak May Mazen Abu Fadel June 2017

14 Trial Update (Acute results) Total Enrolled: 15 patients Average lesion length: 19 cm (4 cm to 44 cm) Acute procedural success (<30%): 100% Acute Device Success (<50%): 71% Distal Embolization: 13% (Both with Filter. Resolved with simple aspiration) Bailout stent: 6.7%

15 JET-SCE Registry Investigator Sponsored Research Jetstream Atherectomy in Peripheral Arterial Interventions: a Single Center Experience Experience with JetStream atherectomy at a single center, single operator in treating the femoropopliteal artery o Stratified to those treated with adjunctive drug coated balloon vs plain old balloon angioplasty post atherectomy This report includes 18-month target lesion revascularization (TLR) rates on patients treated for femoropopliteal (FP) artery disease with Jetstream Atherectomy at a single center, performed by one operator The primary endpoint of the study was clinically driven TLR* Includes procedures from January 2012 through August 2016 o 311 procedures were performed with atherectomy by a single operator at a single center o 77 procedures were excluded Procedures performed with a non Jetstream Atherectomy device Infra-popliteal procedures o The remaining procedures, n=234, were performed in 81 patients 81 patients treated with Jetstream Atherectomy at index 153 atherectomy procedures on follow-up *TLR was calculated by excluding bailout stenting as TLR. Shammas NW. NCVH 2017 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.

16 JET-SCE Registry Investigator Sponsored Research Jetstream Atherectomy in Peripheral Arterial Interventions: a Single Center Experience DM 53.1% (50.9% PTA vs 57.1% DCB, p=0.595) CTO 25.9% (24.5% PTA vs 28.6% DCB, p=0.694) Adjunctive Stent 27.2% (26.4% PTA vs 28.6%,DCB p=0.836) 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.

17 JET-SCE Registry Investigator Sponsored Research Jetstream Atherectomy in Peripheral Arterial Interventions: a Single Center Experience: Acute results Core lab Adjudicated analysis o JS Device Success (<50% stenosis post JS alone): 87.5% o JS Procedural Success (<30% residual final treatment): 94% o Adjunctive Stenting (n=22/81)*: 27.2% o Minimal Luminal Diameter at baseline: 1.5 ± 1.4 mm o Minimal Luminal Diameter post JS: 3.1 ± 1.2 mm o Minimal Luminal Diameter post final treatment: 4.2 ± 0.9 mm Shammas NW. NCVH 2017 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.

18 SCE Jetstream + DCB study Investigator Sponsored Research 81 patients, with de novo or restenotic FP lesions whose symptoms were classified as Rutherford Category I-V were enrolled o o o o o 49.4% male Mean age 68.3 years Mean estimated Treated length Adjunctive PTA: 14.9 ± 9.3 cm DCB: 12.0 ± 6.6 cm No difference between the groups (p=0.1) Adjunctive PTA performed on 53 patients 28 denovo 14 in-stent restenosis 4 non stent restenosis 7 mixed lesions Adjunctive DCB performed on 28 patients (LUTONIX 27, IN.PACT 1) 23 denovo 2 in-stent restenosis 2 non stent restenosis 1 mixed lesion KM Estimate for Freedom from TLR JS+DCB vs JS+PTA TLR rates at 12 M and 18 M were significantly reduced with DCB 12 M Analysis (smaller number of DCB balloon FU>1 yr): Atherectomy with adjunctive DCB (95.2%) compared to Atherectomy with adjunctive PTA (69.8%) (95.2% vs 69.8% p=0.001) Shammas, N. NCVH 2017 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.

19 SCE Jetstream + DCB study Investigator Sponsored Research Analysis on denovo lesions only (excluding adjunctive Zilver PTX stenting) o o Adjunctive PTA performed on 28 denovo (26 excluding Zilver PTX) Adjunctive DCB performed on 23 denovo (21 excluding Zilver PTX) (Four Patients had Zilver PTX Stent with Denovo Lesions: DCB no TLR DCB no TLR POBA no TLR POBA TLR at 6 months, died at 2 years) TLR rate at 12 M was significantly reduced with DCB Atherectomy with adjunctive DCB (95.2%) compared to Atherectomy with adjunctive PTA (69.2%) (91.1% vs 69.2% p=0.006) Shammas, N. NCVH 2017 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.

20 SCE Jetstream + DCB study Investigator Sponsored Research The addition of DCB to atherectomy has markedly improved freedom from TLR (in the 95% range at 1 year) when compared to Jetstream atherectomy alone Shammas, N. NCVH 2017 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.

21 JET-PCB study Investigator Sponsored Research Clinical Study Overview: JET-PCB Trial (Investigator sponsored IDE)* Title Primary Investigator / Sponsor Objective Study Design Subjects Investigational Centers Primary Efficacy Endpoint Primary Safety Endpoint JETStream Atherectomy with Adjunctive Paclitaxel-Coated Balloon Angioplasty vs Plain Old Balloon Angioplasty followed by Paclitaxel-Coated Balloon in Treating Complex Denovo Femoropopliteal Arterial Disease Nicolas W. Shammas, MD Midwest Cardiovascular Research Foundation To evaluate the use of Jetstream Atherectomy (JS) followed by DCB in comparison to the use of plain old balloon angioplasty (POBA) followed by DCB alone in the treatment of complex lesions in femoropopliteal arteries (Rutherford Cat 2-4) Complex lesions are defined: Long lesions ( 10 cm) Moderately or highly calcified lesions Chronic total occlusions (irrespective of length) A prospective, multicenter, 2:1 randomized (JS ath+ranger DCB : PTA+Ranger), 250 subjects (~167 DCB+JS vs 83 PTA+DCB) Up to 25 study sites in US TLR at 1 year, TLR defined as: Retreatment of the index lesion (extended 1 cm prox and dist to the lesion) at 1 year. For the primary endpoint, intra-procedural bail out stenting of the index lesion is considered meeting a TLR endpoint MAE at 30 days Unplanned amputation Total mortality TLR (includes bailout stenting) *IDE approval received from the FDA 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. Ranger DCB is an investigational device and not available for sale in the US.

22 Other Exciting Trials at MCRF EX-PAD-03. Safety and Effectiveness Evaluation of Eximo's B-LaserTM, a hybrid atherectomy device, in Subjects Affected with PAD. (Principal Investigator, MCRF, Shammas NW, 2017) TOBA II BK: Tack Optimized Balloon Angioplasty Study for the below the knee arteries using the Tack Endovascular System. (Principal Investigator, MCRF, Shammas NW, 2017) DISRUPT PAD III. Randomized study of the Shockwave Medical Peripheral Lithoplasty System used in combination with DCB versus standard balloon angioplasty used in combination with DCB to treat moderate and severely calcified femoropopliteal arteries. (Principal Investigator, MCRF, Shammas NW, 2017) DEFINE PCI. Physiologic assessment of coronary stenosis following PCI.. (Principal Investigator, MCRF, Shammas NW, 2017) PARADISE-MI. Entresto in post MI heart failure. (Principal Investigator, MCRF, Shammas NW, 2017) TOBA II. Tack Optimized Balloon Angioplasty Study of the Tack Endovascular System in Femoropoliteal Arteries (TOBA II) (Principal Investigator, MCRF, Shammas NW, 2016)

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