Medtronic Plc. · NYSE:MDT
Medtronic — CIRSE 2019
45 slides from Medtronic's conference presentation, October 2019
Slide 1: Primary Endpoint Results of the IN.PACT AV Access Randomized Trial: Outcomes Through Six Months
PRIMARY ENDPOINT RESULTS OF THE IN.PACT AV ACCESS RANDOMIZED TRIAL: OUTCOMES THROUGH SIX MONTHS Andrew Holden, MBChB, FRANZCR, EBIR Director of Interventional Radiology Auckland Hospital, Auckland, NEW ZEALAND UC202004472bEN © 2019 Medtronic. All Rights Reserved. Medtronic, Medtronic logo and Furthe
Slide 2: Primary Endpoint Results of the IN.PACT AV Access Randomized Trial
PRIMARY ENDPOINT RESULTS OF THE IN.PACT AV ACCESS RANDOMIZED TRIAL: OUTCOMES THROUGH SIX MONTHS Andrew Holden, MBChB, FRANZCR, EBIR Director of Interventional Radiology Auckland Hospital, Auckland, New Zealand 2 Holden, A. Primary Endpoint Results of the IN.PACT AV Access Randomized Trial: Outcomes
Slide 3: Disclosures
DISCLOSURES Speaker name: Andrew Holden, MBChB, FRANZCR, EBIR I have the following potential conflicts of interest to report: X Consulting – Medtronic, Gore, Boston Scientific Employment in industry Stockholder of a healthcare company Owner of a healthcare company Other(s): I do not have
Slide 4: Background
BACKGROUND • In 2016, 500,000 patients in the United States received hemodialysis at least three times a week to treat ESRD1 • Hemodialysis arteriovenous fistula and grafts experience high rates of dysfunction2-5 • Primary patency AVF/AVG through 12 months: 48-80% 24 months: 50-80% 1. United States
Slide 5: Historical use of DCBs in AVF
HISTORICAL USE OF DCBS IN AVF1 The primary outcome measure was set at primary patency @ 1 year defined as freedom from symptomatic recurrent stenosis within the treated circuit area or repeat TLR and was summarized with the odds ratio (OR) and accompanying 95% CI 1. Kitrou P, Spiliopoulos S, Karnaba
Slide 6: Historical use of DCBs in AVF
HISTORICAL USE OF DCBS IN AVF1 The primary outcome measure was set at primary patency @ 1 year defined as freedom from symptomatic recurrent stenosis within the treated circuit area or repeat TLR and was summarized with the odds ratio (OR) and accompanying 95% CI Authors’ Conclusion: “The body of pu
Slide 7: Lutonix AV IDE
LUTONIX AV IDE1 • Multicenter, prospective, randomized, core laboratory and clinical events committee adjudicated trial of 285 subjects • The primary efficacy endpoint was target lesion primary patency at 6 months defined as freedom from clinically driven reintervention on the target lesion or acces
Slide 8: Lutonix AV IDE
LUTONIX AV IDE1 • Multicenter, prospective, randomized, core laboratory and clinical events committee adjudicated trial of 285 subjects • The primary efficacy endpoint was target lesion primary patency at 6 months defined as freedom from clinically driven reintervention on the target lesion or acces
Slide 9: Current use of DCBs in AVF
CURRENT USE OF DCBS IN AVF Meta-analysis of DCB vs POBA for loss of primary patency in AVF at 6 months “In conclusion, DCB angioplasty use in AVF resulted in significant improvement in lesion patency at 3, 6, 12, and 24 months… Ongoing large multi-center RCTs will provide further clarity on the bene
Slide 10: IN.PACT AV Access IDE Study
IN.PACT AV ACCESS IDE STUDY Objective: Evaluate the safety and effectiveness of the IN.PACT™ AV drug-coated balloon (DCB) compared to percutaneous transluminal angioplasty (PTA) for treatment of de-novo or restenotic obstructive lesions of native arteriovenous fistulae (AVF) in the upper extremity P
Slide 11: IDE Study Design
IN.PACT AV ACCESS IDE STUDY DESIGN • Prospective, global, multicenter, 1:1 randomized, single-blinded study • 330 patients • Up to 5-year follow-up • Lesions up to 10 cm in length in the native AVF • Independent and blinded Duplex Ultrasound Core Lab1, Angiographic Core Lab2, and Clinical Events Com
Slide 12: Investigators
IN.PACT AV ACCESS INVESTIGATORS Investigator Site Location Investigator Site Location Levester Kirksley Cleveland Clinic Cleveland, OH John Ross Dialysis Access Institute Orangeburg, SC Sanjay Misra Mayo Clinic Rochester, MN Jeffrey Hoggard North Carolina Nephrology Raleigh, NC Sanford University of
Slide 13: Key Inclusion/Exclusion Criteria
IN.PACT AV ACCESS KEY INCLUSION/EXCLUSION CRITERIA Inclusion Exclusion Life expectancy of ≥ 12 months • Undergone prior intervention of access site within 30 days of index procedure Native AV fistula created ≥ 60 days prior to the index • Target AVF previously had or currently has a thrombosis p
Slide 14: Key Inclusion/Exclusion Criteria
IN.PACT AV ACCESS KEY INCLUSION/EXCLUSION CRITERIA Inclusion Exclusion Life expectancy of ≥ 12 months • Undergone prior intervention of access site within 30 days of index procedure Native AV fistula created ≥ 60 days prior to the index • Target AVF previously had or currently has a thrombosis p
Slide 15: Key Lesion Criteria
IN.PACT AV ACCESS KEY LESION CRITERIA Inclusion • Patient has a de novo and/or non-stented restenotic lesion located between the arteriovenous anastomosis and axillosubclavian junction with ≥ 50% stenosis • Target lesion or a tandem lesion that is ≤ 100 mm in length • Note: Tandem lesions may be enr
Slide 16: Primary Endpoints
IN.PACT AV ACCESS PRIMARY ENDPOINTS Primary Safety Endpoint: Serious Adverse Event Rate within 30 Days Defined as the Serious Adverse Event (SAE) rate involving the AV access circuit through 30 days post-procedure Primary Effectiveness Endpoint: Target Lesion Primary Patency Rate through 6 Months
Slide 17: Baseline Characteristics
IN.PACT AV ACCESS BASELINE CHARACTERISTICS IN.PACT AV DCB Standard PTA Baseline Demographics P-value (n=170) (n=160) Age (yrs) (mean ± SD) 65.8 ± 13.1 65.5 ± 13.4 0.837 Male 65.9% (112/170) 63.1% (101/160) 0.646 Hypertension 91.2% (155/170) 94.4% (151/160) 0.295 Hyperlipidemia 54.1% (92/170) 52.5% (
Slide 18: Baseline Characteristics
IN.PACT AV ACCESS BASELINE CHARACTERISTICS IN.PACT AV DCB Standard PTA Baseline Demographics P-value (n=170) (n=160) Age (yrs) (mean ± SD) 65.8 ± 13.1 65.5 ± 13.4 0.837 Male 65.9% (112/170) 63.1% (101/160) 0.646 Hypertension 91.2% (155/170) 94.4% (151/160) 0.295 Hyperlipidemia 54.1% (92/170) 52.5% (
Slide 19: AVF Type
IN.PACT AV ACCESS AVF TYPE Radiocephalic Brachiocephalic Brachiobasilic Standard PTA (n=160) 50.0% 36.3% 9.4% P=0.918 IN.PACT AV DCB (n=170) 50.6% 36.5% 10.0% 0% 20% 40% 60% 80% 100% AVF type locations are site-reported ; AVF, arteriovenous fistula; DCB, drug-coated balloon; PTA, percutaneous transl
Slide 20: AVF Characteristics
IN.PACT AV ACCESS AVF CHARACTERISTICS IN.PACT AV DCB Standard PTA AVF Characteristics1 P-value (n=170) (n=160) Lesion Length (mm; mean ± SD) 46.9 ± 28.1 40.0 ± 25.7 0.021 Target Arm 0.449 Right 23.5% (40/170) 27.5% (44/160) Left 76.5% (130/170) 72.5% (116/160) Dominant Arm 22.4% (38/170) 24.4% (39/1
Slide 21: Lesion Characteristics
IN.PACT AV ACCESS LESION CHARACTERISTICS IN.PACT AV DCB Standard PTA 6 Lesion Characteristics1 P-value (n=170) (n=160) 5 3 Lesion Type 0.905 4 De Novo 30.0% (51/170) 30.6% (49/160) 1 Restenotic 70.0% (119/170) 69.4% (111/160) 2 Target Lesion Location1 0.310 Arterial Inflow 2.4% (4/170) 4.4% (7/160)
Slide 22: Lesion Characteristics
IN.PACT AV ACCESS LESION CHARACTERISTICS IN.PACT AV DCB Standard PTA 6 Lesion Characteristics P-value (n=170) (n=160) 5 3 Lesion Type 0.905 4 De Novo 30.0% (51/170) 30.6% (49/160) 1 Restenotic 70.0% (119/170) 69.4% (111/160) 2 Target Lesion Location1 0.310 Arterial Inflow 2.4% (4/170) 4.4% (7/160) A
Slide 23: Clinical Characteristics
IN.PACT AV ACCESS CLINICAL CHARACTERISTICS IN.PACT AV DCB Standard PTA Clinical Characteristics P-value (n=170) (n=160) Presenting Clinical Symptoms Indicating AV Access Dysfunction Decreased Blood Flow 63.5% (108/170) 55.0% (88/160) 0.118 Elevated Venous Pressures 15.9% (27/170) 20.0% (32/160) 0.38
Slide 24: Clinical Characteristics
IN.PACT AV ACCESS CLINICAL CHARACTERISTICS IN.PACT AV DCB Standard PTA Clinical Characteristics P-value (n=170) (n=160) Presenting Clinical Symptoms Indicating AV Access Dysfunction Decreased Blood Flow 63.5% (108/170) 55.0% (88/160) 0.118 Elevated Venous Pressures 15.9% (27/170) 20.0% (32/160) 0.38
Slide 25: Procedural Characteristics
IN.PACT AV ACCESS PROCEDURAL CHARACTERISTICS IN.PACT AV DCB Standard PTA Procedural Characteristics1 P-value (n=170) (n=160) Minimum Lumen Diameter (mm) Pre-procedure 2.7 ± 1.6 (170) 2.8 ± 1.7 (159) 0.731 After pre-dilatation 4.9 ± 1.9 (167) 5.2 ± 2.0 (159) 0.269 After index procedure 5.5 ± 1.9 (170
Slide 26: Primary Effectiveness Endpoint
IN.PACT AV ACCESS PRIMARY EFFECTIVENESS ENDPOINT IN.PACT AV DCB Standard PTA Difference Primary Effectiveness Endpoint P-value1 (n=170) (n=160) [95% CI] Target Lesion Primary Patency2 through 210 days3 82.2% (125/152) 59.5% (88/148) 22.8% [12.8%, 32.8%] < 0.001 Clinically-driven target lesion revasc
Slide 27: Primary Effectiveness Endpoint: 6-Month Kaplan-Meier Plot
IN.PACT AV ACCESS - PRIMARY EFFECTIVENESS ENDPOINT 6-MONTH KAPLAN-MEIER PLOT 27 Holden, A. Primary Endpoint Results of the IN.PACT AV Access Randomized Trial: Outcomes Through Six Months. CIRSE 2019
Slide 28: Access Circuit Patency
IN.PACT AV ACCESS – ACCESS CIRCUIT PATENCY IN.PACT AV DCB Standard PTA Difference Access Circuit Patency P-value1 (n=170) (n=160) [95% CI] Access circuit primary patency2 73.2% (112/153) 48.0% (71/148) 25.2% [14.6%, 35.9%] < 0.001 Re-intervention in access circuit 25.5% (39/153) 50.7% (75/148) -25.2
Slide 29: Access Circuit Patency: 6-Month Kaplan-Meier Plot
IN.PACT AV ACCESS - ACCESS CIRCUIT PATENCY 6-MONTH KAPLAN-MEIER PLOT 29 Holden, A. Primary Endpoint Results of the IN.PACT AV Access Randomized Trial: Outcomes Through Six Months. CIRSE 2019
Slide 30: Primary Safety Endpoint
IN.PACT AV ACCESS PRIMARY SAFETY ENDPOINT IN.PACT AV DCB Standard PTA P-value1 for non- Primary Safety Endpoint (n=170) (n=160) inferiority Serious adverse events involving the 4.2% (7/166) 4.4% (7/158) 0.002 arteriovenous access circuit within 30 days2, 3 Arteriovenous fistula occlusion 0.6% (1/166
Slide 31: Revascularizations
IN.PACT AV ACCESS REVASCULARIZATIONS IN.PACT AV DCB Standard PTA Difference Revascularizations P-value1 (n=170) (n=160) [95% CI] Any target lesion revascularization 16.3% (25/153) 39.9% (59/148) -23.5% [-33.4%, -13.7%] < 0.001 Number of interventions required to maintain target lesion patency throug
Slide 32: Freedom from SAE: 6-Month Kaplan-Meier Plot
IN.PACT AV ACCESS - FREEDOM FROM SAE 6-MONTH KAPLAN-MEIER PLOT Freedom from SAE through 180 days is compared using a log-rank test and it is tested for superiority between two treatment groups 32 Holden, A. Primary Endpoint Results of the IN.PACT AV Access Randomized Trial: Outcomes Through Six Mont
Slide 33: FDA Panel Question: Paclitaxel in Other Vessel Beds
FDA PANEL QUESTION: PACLITAXEL IN OTHER VESSEL BEDS 33 Holden, A. Primary Endpoint Results of the IN.PACT AV Access Randomized Trial: Outcomes Through Six Months. CIRSE 2019
Slide 34: FDA Panel Question: Paclitaxel in Other Vessel Beds
FDA PANEL QUESTION: PACLITAXEL IN OTHER VESSEL BEDS 34 Holden, A. Primary Endpoint Results of the IN.PACT AV Access Randomized Trial: Outcomes Through Six Months. CIRSE 2019
Slide 35: FDA Panel Question: Paclitaxel in Other Vessel Beds
FDA PANEL QUESTION: PACLITAXEL IN OTHER VESSEL BEDS US 2-year mortality of patients on hemodialysis 33.2%1 1. USRDS 2018 Chapter 5: Mortality, Table 5.3 35 Holden, A. Primary Endpoint Results of the IN.PACT AV Access Randomized Trial: Outcomes Through Six Months. CIRSE 2019
Slide 36: Mortality with Paclitaxel Devices in Dialysis Access
MORTALITY WITH PACLITAXEL DEVICES IN DIALYSIS ACCESS “The analysis found no difference in short- to midterm mortality among patients treated with a drug-coated balloon compared with PTA. With proven benefit and no evidence of harm, the authors recommend ongoing use of PCB for the failing dialysis ac
Slide 37: KM Mortality Through 12 Months
IN.PACT AV ACCESS KM MORTALITY THROUGH 12 MONTHS 37 Holden, A. Primary Endpoint Results of the IN.PACT AV Access Randomized Trial: Outcomes Through Six Months. CIRSE 2019
Slide 38: Conclusions
IN.PACT AV ACCESS CONCLUSIONS • The IN.PACT AV Access Trial is a multi-center, prospective RCT comparing DCB to standard PTA in AV access that met its primary effectiveness endpoint • Primary effectiveness endpoint met: 6-month target lesion primary patency was 82.2% in DCB compared to 59.5% in PTA
Slide 39: Conclusions
IN.PACT AV ACCESS CONCLUSIONS • The IN.PACT AV Access Trial is a multi-center, prospective RCT comparing DCB to standard PTA in AV access that met its primary effectiveness endpoint • Primary effectiveness endpoint met: 6-month target lesion primary patency was 82.2% in DCB compared to 59.5% in PTA
Slide 40: Conclusions
IN.PACT AV ACCESS CONCLUSIONS • The IN.PACT AV Access Trial is a multi-center, prospective RCT comparing DCB to standard PTA in AV access that met its primary effectiveness endpoint • Primary effectiveness endpoint met: 6-month target lesion primary patency was 82.2% in DCB compared to 59.5% in PTA
Slide 41: Conclusions
IN.PACT AV ACCESS CONCLUSIONS • The IN.PACT AV Access Trial is a multi-center, prospective RCT comparing DCB to standard PTA in AV access that met its primary effectiveness endpoint • Primary effectiveness endpoint met: 6-month target lesion primary patency was 82.2% in DCB compared to 59.5% in PTA
Slide 42: Primary Endpoint Results of the IN.PACT AV Access Randomized Trial
PRIMARY ENDPOINT RESULTS OF THE IN.PACT AV ACCESS RANDOMIZED TRIAL: OUTCOMES THROUGH SIX MONTHS Andrew Holden, MBChB, FRANZCR, EBIR Director of Interventional Radiology Auckland Hospital, Auckland, New Zealand 42 Holden, A. Primary Endpoint Results of the IN.PACT AV Access Randomized Trial: Outcomes
Slide 43: Brief Statement
BRIEF STATEMENT Indications for Use: The IN.PACT™ AV Paclitaxel-coated PTA Balloon Catheter is indicated for percutaneous transluminal angioplasty, after appropriate vessel preparation, for the treatment of obstructive lesions up to 100 mm in length in the native arteriovenous dialysis fistulae with
Slide 44: Brief Statement
BRIEF STATEMENT Precautions • This product should only be used by physicians trained in percutaneous transluminal angioplasty (PTA). • Assess risks and benefits before treating patients with a history of severe reaction to contrast agents. Identify allergic reactions to contrast media and antiplatel
Slide 45: Thank You
THANK YOU UC202004472bEN © 2019 Medtronic. All Rights Reserved. Medtronic, Medtronic logo and Further, Together are trademarks of Medtronic. TM* Third party brands are trademarks of their respective owners. All other brands are trademarks of a Medtronic company. For Distribution in the USA Only. 10/