1 1 UNITED STATES OF AMERICA DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION + + + CENTER FOR DEVICES AND RADIOLOGICAL HEALTH MEDICAL DEVICES ADVISORY COMMITTEE + + + CIRCULATORY DEVICES PANEL + + + February 23, 2017 8:00 a.m. Hilton Washington DC North 620 Perry Parkway Gaithersburg, Maryland PANEL MEMBERS: RICHARD PAGE, M.D. Panel Chair GEORGE W. VETROVEC, M.D., MACC, MScai Voting Member DAVID NAFTEL, Ph.D. Voting Member JOAQUIN E. CIGARROA, M.D. Voting Member DAVID D. YUH, M.D., FACS, FACC Temporary Non-Voting Member JEFFREY S. BORER, M.D. Temporary Non-Voting Member JOHN C. SOMBERG, M.D. Temporary Non-Voting Member JEFFREY BRINKER, M.D. Temporary Non-Voting Member DAVID C. GOOD, M.D. Temporary Non-Voting Member ERICK MAGNUS OHMAN, M.B., FRCPI, FACC Temporary Non-Voting Member GUERRY M. PEAVY, Ph.D. Temporary Non-Voting Member DONNA RAE ROBERTS, M.D. Temporary Non-Voting Member JOHN W. HAMMON, JR., M.D. Temporary Non-Voting Member LORI E. DODD, Ph.D. Temporary Non-Voting Member KEVIN M. DUFF, Ph.D., ABPP(CN) Temporary Non-Voting Member NAVEEN THURAMALLA, M.S., CCRP Industry Representative NAFTALI Z. FRANKEL, M.S. Consumer Representative PHILLIP POSNER, Ph.D. Patient Representative EVELLA WASHINGTON Designated Federal Officer This transcript has not been edited or corrected, but appears as received from the commercial transcribing service. Accordingly, the Food and Drug Administration makes no representation as to its accuracy. Free State Reporting, Inc. 1378 Cape St. Claire Road Annapolis, MD 21409 (410) 974-0947 2 2 FDA REPRESENTATIVES: RANDALL BROCKMAN, M.D. Clinical Deputy Director Office of Device Evaluation STEPHANIE CACCOMO Press Contact FDA PRESENTERS: CDR SADAF A. TOOR, M.S. Biomedical Engineer U.S. Public Health Service Peripheral Interventional Devices Branch Division of Cardiovascular Devices Office of Device Evaluation DONNA BUCKLEY, M.D., M.S. Division of Cardiovascular Devices Office of Device Evaluation LI MING DONG, Ph.D. Division of Biostatistics Office of Surveillance and Biometrics Free State Reporting, Inc. 1378 Cape St. Claire Road Annapolis, MD 21409 (410) 974-0947 3 3 SPONSOR PRESENTERS: THOMAS ENGELS Vice President of Clinical Affairs Claret Medical, Inc. MARTIN B. LEON, M.D. Professor of Medicine Columbia University RENU VIRMANI, M.D. President, CVPath Institute, Inc. Clinical Professor, George Washington University WILLIAM A. GRAY, M.D. System Chief of the Division of Cardiovascular Disease Lankenau Medical Center Main Line Health AZIN PARHIZGAR, Ph.D. President and CEO Claret Medical, Inc. SPONSOR ADVISORS: ROBERT ZIVADINOV, M.D., Ph.D. Professor of Neurology Director, Buffalo Neuroimaging Analysis Center MICHAEL DWYER, Ph.D. Director of Technical Imaging Buffalo Neuroimaging Analysis Center Assistant Professor of Neurology University of Buffalo ROSEANN WHITE, M.A. Director, Pragmatic Clinical Trial Statistics Duke Clinical Research Institute RONALD LAZAR, Ph.D. Professor of Neuropsychology Columbia University Medical Center Free State Reporting, Inc. 1378 Cape St. Claire Road Annapolis, MD 21409 (410) 974-0947 4 4 OPEN PUBLIC HEARING SPEAKERS: JIM McCUTCHEON, M.D. Private Citizen NICOLAS M. VAN MIEGHEM, M.D., Ph.D., FESC The Thoraxcenter, Erasmus MC Rotterdam, the Netherlands JOCHEN WÖHRLE, Prof. Dr. Head, Interventional Cardiology University of Ulm Ulm, Germany DAVID LANGE, M.D. Cedars-Sinai Medical Center ADNAN H. SIDDIQUI, M.D., Ph.D. University of Buffalo American Association of Neurological Surgeons Congress of Neurological Surgeons Society of NeuroInterventional Surgeons SAIF ANWARUDDIN, M.D. Perelman School of Medicine University of Pennsylvania LARRY RUVO Keep Memory Alive Cleveland Clinic Lou Ruvo Center for Brain Health ROBERT E. ECKLEY Patient SUSAN ROCKENBACH Daughter of Marie Bartman, Patient Free State Reporting, Inc. 1378 Cape St. Claire Road Annapolis, MD 21409 (410) 974-0947 5 5 INDEX PAGE CALL TO ORDER - Richard Page, M.D. 8 PANEL INTRODUCTIONS 8 CONFLICT OF INTEREST STATEMENT - Evella Washington 10 SPONSOR PRESENTATION Introduction - Thomas Engels 14 Background - Martin B. Leon, M.D. 17 Histopathology - Renu Virmani, M.D. 27 SENTINEL Trial Effectiveness - Martin B. Leon, M.D. 30 SENTINEL Results in the Context of Neuroprotection History - William A. Gray, M.D. 35 Concluding Remarks - Azin Parhizgar, Ph.D. 38 SPONSOR Q&A 41 FDA PRESENTATION Introduction and Summary of SENTINEL Study Design - CDR Sadaf A. Toor, M.S. 58 SENTINEL Clinical Results and Considerations - Donna Buckley, M.D., M.S. 63 SENTINEL Statistical Results and Considerations - Li Ming Dong, Ph.D. 70 Conclusions - CDR Sadaf A. Toor, M.S. 75 FDA Q&A 76 PANEL DELIBERATIONS 89 Free State Reporting, Inc. 1378 Cape St. Claire Road Annapolis, MD 21409 (410) 974-0947 6 6 INDEX PAGE OPEN PUBLIC HEARING Jim McCutcheon, M.D. 102 Nicolas M. Van Mieghem, M.D., Ph.D., FESC 104 Jochen Wöhrle, Prof. Dr. 106 David Lange, M.D. 109 Adnan H. Siddiqui, M.D., Ph.D. 112 Saif Anwaruddin, M.D. 115 Larry Ruvo 116 Robert E. Eckley 118 Susan Rockenbach 119 PANEL DELIBERATIONS 121 FDA QUESTIONS TO THE PANEL Question 1 154 Question 2 155 Question 3 167 Question 4 177 Question 5 183 Question 6 186 Question 7 189 Question 8 192 Question 9 195 Free State Reporting, Inc. 1378 Cape St. Claire Road Annapolis, MD 21409 (410) 974-0947 7 7 INDEX PAGE SUMMATIONS FDA - Donna Buckley, M.D., M.S. 203 Sponsor - Martin B. Leon, M.D. 204 ADJOURNMENT 218 Free State Reporting, Inc. 1378 Cape St. Claire Road Annapolis, MD 21409 (410) 974-0947 8 8 M E E T I N G (8:09 a.m.) DR. PAGE: Good morning, everyone. Sorry to be starting a little bit late. I'd like to call this meeting of the Circulatory System Devices Panel of the Medical Devices Advisory Committee to order. My name is Richard Page. I'm Chair of the Panel. I'm also chair of medicine at the University of Wisconsin in Madison, and I am a clinical cardiac electrophysiologist by training. I note for the record that the Panel members present constitute a quorum as required by 21 C.F.R. Part 14. I would also like to add that the Panel members participating in today's meeting have received training in FDA device law and regulations. For today's agenda, the Panel will discuss and make recommendations on information regarding the de novo request for Claret Medical, Incorporated's SENTINEL Cerebral Protection System. FDA is seeking guidance from its expert panel to decide if the clinical performance of this device is safe and effective and supports the proposed intended use. If the performance is acceptable, FDA is seeking guidance on the types of information needed in the device labeling to support the safe and effective use of the device. Before we begin, I will ask our distinguished Panel members and the FDA staff seated at the table to introduce themselves. Please state your name, your area of expertise, your position, and affiliation. I'd first like to start with Dr. Randall Brockman, who is sitting in for Dr. Zuckerman today. Dr. Brockman. DR. BROCKMAN: Good morning. Thank you. I'm Randy Brockman. I'm the Clinical Deputy Director in the Office of Device Evaluation, and as Dr. Page mentioned, I'm sitting in for Bram Zuckerman, who wasn't able to join us this morning. Free State Reporting, Inc. 1378 Cape St. Claire Road Annapolis, MD 21409 (410) 974-0947 9 9 DR. VETROVEC: George Vetrovec, BCU Medical Center, Professor Emeritus, interventional cardiology. DR. SOMBERG: John Somberg. I'm a Professor of Medicine, Cardiology, and Pharmacology at Rush University in Chicago. DR. OHMAN: Magnus Ohman, cardiologist at Duke University Medical Center in North Carolina, and I'm vice chair of medicine at Duke. DR. HAMMON: I'm John Hammon and I am a cardiothoracic surgeon, and I'm on the faculty of Wake Forest University Medical Center in Winston-Salem, North Carolina. DR. DUFF: Kevin Duff. I'm at the University of Utah. I am a professor in the department of neurology and a clinical neuropsychologist. DR. PEAVY: I'm Guerry Peavy, University of California, San Diego, in the department of neurosciences, and my area of expertise is neuropsychology. DR. BRINKER: I'm Jeff Brinker, Professor of Medicine and Radiology and an interventional cardiologist at Johns Hopkins. DR. YUH: Good morning. I'm David Yuh. I'm the chairman of the department of surgery at Stamford Hospital in Stamford, Connecticut, and my area of expertise is in valvular surgery and cardiac surgery. MS. WASHINGTON: My name is Evella Washington. I am the DFO. DR. NAFTEL: My name's David Naftel. I am a biostatistician in the division of cardiac surgery at the University of Alabama at Birmingham. DR. CIGARROA: I'm Joaquin Cigarroa. I'm the clinical chief for the Knight Cardiovascular Institute at OHSU, Clinical Professor of Medicine and an interventional cardiologist. DR. DODD: I'm Lori Dodd. I am a biostatistician at the National Institute of Allergy and Infectious Diseases. Free State Reporting, Inc. 1378 Cape St. Claire Road Annapolis, MD 21409 (410) 974-0947 1010 DR. BORER: My name is Jeff Borer, and I am a cardiologist. I'm Professor of Medicine, Cell Biology, Radiology, and Public Health, and former chairman of medicine and the chief of cardiology at SUNY Downstate in New York City. DR. GOOD: Good morning. I'm David Good, and I'm Professor of Neurology at Penn State College of Medicine at Hershey. My clinical interests are stroke and stroke rehabilitation. DR. ROBERTS: I'm Donna Roberts. I am an Associate Professor of Radiology at the Medical University in South Carolina, and my specialty is Neuroradiology. MR. THURAMALLA: Good morning. I'm Naveen Thuramalla, Vice President of Regulatory Affairs at ARKRAY. On this Panel, I serve as an Industry Representative.