AVERT System in PCI Procedures for the Reduction of Contrast Volume - PowerPoint PPT Presentation

Randomized Controlled Trial to Evaluate the AVERT System in PCI Procedures for the Reduction of Contrast Volume Use and Contrast- Induced Acute Kidney Injury RESULTS FROM THE AVERT TRIAL Roxana Mehran, , MD Professo sor of of Medicine (Ca (Cardiolo logy) an and Popula lation He Health Evid idence an and Polic licy Di Director of of In Interv rventional Car Cardio iovascular Rese esearch an and Clin Clinic ical l Tria ials The Ica Icahn Sc School of of Medicine at Mount Sin Sinai, New York ork, NY on on beh ehalf of of AVERT In Inves esti tigators

Conflict of f In Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. These relationships may lead to bias in my presentation. Affiliation/Financial Relationship Company • • Grant/Research Support The Medicines Co., BMS, Astra (Institutional) Zeneca, Lilly/Daiichi Sankyo, Bayer • Janssen (J+J), Abbott Vascular • Advisory Board • Medscape • Consulting Fees/Honoraria

Backg kground: Contr trast-Induced Acute Kid idney In Inju jury ry • Contrast-induced acute kidney injury (CI-AKI) can occur in up to 20-30% of patients with prior renal impairment and is associated with increased morbidity and mortality • Risk factors for CI-AKI can be categorized as non-modifiable (i.e. patient co-morbidities) and modifiable (i.e. procedure related) factors 1 • Contrast volume is a critical modifiable risk factor that the interventional cardiologist can potentially control during the procedure 1. Mehran R, et al. J Am Coll Cardiol 2004; 44(7): 1393-1399.

Minimizing Contrast Usage Insights from NCDR Cath-PCI Registry 1 • Iodinated contrast hypothesized to cause AKI/CIN • Increasing contrast volume increases risk of AKI/CIN • Data suggest minimizing contrast dose 1 Tsai, et al. JACC, Jan 2014, 1-9. 4

AVERT System • Consists of a Contrast Modulator and Modulation Reservoir • Contrast Modulator applies adjustable resistance along the Reservoir line. Once the operator injects the media, part of the contrast is administered to the patient, while the balance (excess contrast) is diverted to the Modulation Reservoir. • The amount of contrast diverted can be adjusted per physician preference by moving the pin on the Contrast Modulator to alter the resistance along the diversion line.

AVERT Pil ilot Study • 21 patients at a single investigational center • Key findings:  Image quality comparable with AVERT ON vs OFF  Safe – no device-related serious adverse events  Effective – 40% reduction of contrast injected with OFF AVERT ON vs OFF (comparison shots)  Independent, blinded analysis verified reflux reduction in comparison shots. ON Source: Kaye et al., Catheter Cardiovasc Interv. 2013 Dec 10. [Epub ahead of print] 6

AVERT – Stu tudy Objectives Primary  Efficacy:  Reduction of contrast volume used in AVERT + hydration compared to hydration only  Reduction in incidence of CI-AKI [defined as a serum creatinine (SCr) increase >0.3 mg/dl from baseline]  Safety:  Evaluation of device safety Secondary  Evaluation of image quality  Rate of protocol defined severe adverse events through 30 days of follow-up  Change in kidney function

AVERT – Statistical Assumptions • Rejection of the null hypothesis will indicate a statistically significant difference in the mean volume of contrast used; the device will be considered superior if the device group mean is lower and the above test is statistically significant. This objective will be assessed with a two sample t-test of means. at the one-sided 0.025 alpha level. Power Calculation • one-sided 0.025 alpha level. The control group population CIN proportion was assumed to be 22.5% and the treatment group rate of CIN was assumed to be 13.05%, a 42% relative reduction. Based on these assumptions, a total sample size of 548 evaluable subjects will provide 80% power for the primary efficacy endpoint • This sample size will provide 90% power for objective 1.

- Exclusions - T RIAL *LV functional assess using contrast P T HIGHLY LIKELY TO HAVE PCI media *Unable to undergo protocol-specified w/ baseline eGFR 20-30 - OR – peri-procedural hydration >30 to <60 w/ 2 comorbidities *Acute renal failure/unstable renal function *Acute STEMI within 72 hrs of n = 578 | 45 sites currently having STEMI T REATMENT C ONTROL Randomized 1:1 CIN within 5 days post-procedure Central lab B LOOD D RAWS Mobile blood draw Blood draw kits Discharge, 48, 72 (96 & 120 if needed) Pt transport P HONE V ISIT 30 day 9

Major In Inclusion Criteria • Planned definite PCI, planned staged PCI, or coronary diagnostic procedure anticipated to become PCI • At risk for developing CI-AKI • eGFR (ml/min) > 20 and < 30 or • eGFR (ml/min) > 30 and < 60 with at least two co-morbidities o NYHA III/IV o Diabetes: type I or II requiring insulin or type II on oral medications o Albuminuria (+2) o Anemia (<12 mg/ml female; <13 mg/ml male) o Medically treated hypertension o > 75 years of age

Hydration Regimen Peri-Procedural Hydration • Required for all patients • Isotonic NaCl or NaHCO 3 1.0-1.5 ml/kg/hr (could be adjusted for subjects unable to tolerate higher volumes) • PCI – 2 hrs pre-procedure / 4-12 hrs post-procedure • Diagnostic – 2 hrs pre-procedure / institutional SOC post-procedure N-acetylcysteine • Allowed per investigator’s discretion

Stu tudy Organization Principal Investigator, Roxana Mehran, MD • Mt Sinai Icahn School of Medicine Steering Committee • Gregg Stone, MD, Chair – Cardiovascular Research Foundation • Somjot Brar, MD – Kaiser Permanente, Los Angeles, CA • Hitinder Gurm, MD – University of Michigan, Ann Arbor, MI • Anand Prasad, MD – University of Texas, San Antonio, TX • James Tumlin, MD – University of Tennessee, Chattanooga, TN Statistics • NAMSA, Minneapolis, MN Adverse Event Adjudication • Cardiovascular Research Foundation Sponsor/Project & Data Management/Monitoring • Osprey Medical, Minneapolis MN

Enrolling Sit ites - 39 Principal Total # Principal Total # Site Site Investigator Enrolled Investigator Enrolled Stanford Hospital and Clinics David Lee 9 North Mississippi Medical Center Barry Bertolet 83 North Carolina Heart & Vascular Institute Lee Jobe 71 Sentara CV Research Inst./Norfolk General Paul Mahoney 9 Gateway Cardiovascular Research Center Bassam Al-Joundi 31 Heart and Vascular Institute of FLA Patrick Cambier 9 Kaiser Permanente LA Medical Center Somjot Brar 29 UCSD Medical Center Ehtisham Mahmud 8 Mount Sinai Hospital, New York George Dangas 27 Ochsner Clinic Foundation Rajan Patel 8 Tallahassee Memorial Hospital Wayne Batchelor 24 VA Long Beach Medical Center Arnold Seto 8 University of Florida College of Medicine Dominick Angiolillo 23 York Hospital Paul Tolerico 7 The Moses H. Cone Memorial Hospital Michael Cooper 19 Houston Methodist Research Foundation Alpesh Shah 7 Mayo Clinic Hospital Patricia Best 18 Cardiovascular Associates of East Texas Jeffery Carr 6 University of Chicago Medical Center Atman Shah 18 University of Illinois at Chicago Amer Ardati 5 Jewish Hospital Naresh Solankhi 17 Oklahoma Heart Hospital Thomas McGarry 4 VA North Texas Health Care System Subhash Banerjee 17 Abbott Northwestern Hospital M. Nicholas Burke 3 St. Vincent's Medical Center Peter Kuhlman 16 Allegheny General David Lasorda 3 U Texas Health Science Center Anand Prasad 15 Auckland City Hospital, New Zealand Peter Ruygrok 3 South Carolina Heart Hospital Bashir Lone 14 St. Joseph's Hospital of Atlanta George Chang 2 Heart Center Alfred Hospital, Australia Stephen Duffy 14 Baylor St. Luke's Medical Center Guilherme Silva 2 St. Luke's Hospital Anthony Hart 12 Norton Audubon Hospital Divyesh Bhatka 2 Baptist Memorial Hospital David Wolford 11 Coliseum Medical Center Maria Bartlett 2 The Heart Hospital Baylor Plano David Brown 2 Joseph Thomas 10 Harbor UCLA Medical Center Emory University Hospital Midtown Gautam Kumar 10

Patient Flow N=620 Consented and Screened N=578 Randomized N=286 Control N=292 AVERT No Procedure (N=9) No Procedure (N=2) N=284 Procedure Completed N=283 Procedure Completed Evaluated for Contrast Reduction Evaluated for Contrast Reduction Withdrew Post- Withdrew Withdrew Procedure (N=2) Pre-30 Day Pre-30 Day FU (N=12) FU (N=4) N=281 Evaluated for CI-AKI N=282* Evaluated for CI-AKI N=280 Completed 30 Day Visit N=269 Completed 30 Day Visit * 2 control group patients completed 30 day study follow-up but are missing SCr and CI-AKI status

Key Baseline Characteristic ics by Treatment Group Control AVERT P-value (N=286) (N=292) Age (years) 72.3 ± 9.4 71.0 ± 9.3 0.11 Age > 75, n (%) 135 (47.2) 119 (40.8) Female Gender, n (%) 113 (39.5) 114 (39.0) 0.93 BMI (kg/m 2 ) 30.9 ± 7.0 31.1 ± 6.8 0.69 eGFR (mL/min/1.73m 2 ) 45.6 ± 10.7 45.6 ± 10.7 0.96 Previous MI, n (%) 104 (36.4) 105 (36.0) 0.93 Previous CABG, n (%) 92 (32.2) 90(30.8) 0.78 Previous PCI, n (%) 132 (46.2) 154 (52.7) 0.11 Hypertension, n (%) 283 (99.0) 288 (98.6) 1.00 CHF, n (%) 88 (30.8) 99 (33.9) 0.42 Diabetes, n (%) 182 (63.6) 193 (66.1) 0.54 Anemia, n (%) 112 (39.2) 118 (40.4) 0.79 P-values based on t- test, Wilcoxon or Fisher’s exact test