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Ranolazine in High Risk ICD Patients

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Ranolazine in High Risk ICD Patients Ranolazine in High Risk ICD Patients ClinicalTrials.gov Identifier: NCT01215253 Late Sodium Current Blockade in High-Risk ICD Patients Ranolazine ICD Trial (RAID) Version 6.0 September 5, 2014 Sponsored by University of Rochester Funding Body National Institutes of Health (NIH)/ National Heart, Lung & Blood Institute (NHLBI) U01 HL96607-01A1 and U01 HL96610-01A1 Prinicpal Investigators: PI: Wojciech Zareba, MD, PhD Co-PI: Arthur J. Moss, MD Co-Investigators David Huang, MD, Katia Noyes, PhD, University of Rochester Medical Center 265 Crittenden Blvd, Rochester, NY 14642 James Daubert, MD Duke University Medical Center 2301 Erwin Road Durham, NC 27710 Coordinators Suzanne Robertson, PhD, CCRA Mary W. Brown, MS RAID Protocol Version 6.0 Page 1 of 47 September 5, 2014 Ranolazine in High Risk ICD Patients TABLE OF CONTENTS A. SPECIFIC AIMS .............................................................................................................................................. 4 B. BACKGROUND AND SIGNIFICANCE ....................................................................................................... 5 B.1. Population at High Risk of Cardiac Events ................................................................................................. 5 B.2. Treatment Options for High-Risk Patients .................................................................................................. 8 B.3. Late Sodium Currant Blockade ................................................................................................................... 9 B.4. Significance of the Trial ............................................................................................................................ 10 C. PRELIMINARY STUDIES ........................................................................................................................... 11 C.1. Prior Studies Documenting High Risk of Cardiac Events in ICD Patients ............................................... 11 C.1.1. Secondary Prevention of Mortality .................................................................................................... 11 C.1.2. Primary Prevention of Mortality in Ischemic Cardiomyopathy ......................................................... 12 C.1.3. Nonischemic Cardiomyopathy Patients ............................................................................................. 13 C.2. Ranolazine as Antiarrhythmic Compound (In Vitro Data) ....................................................................... 14 C.3 Data Regarding Clinical use of Ranolazine ............................................................................................... 17 C.5. Prior Experience of Investigators .............................................................................................................. 20 D. RESEARCH DESIGN AND METHODS .................................................................................................... 20 D.1. Introduction ............................................................................................................................................... 20 D.2. Specific Aims of the Proposed Trial ......................................................................................................... 20 D.2.1. Primary aim of the study ................................................................................................................... 20 D.2.2. Secondary aims of the study .............................................................................................................. 21 D.3. Overall Design of the Trial ....................................................................................................................... 22 D.3.1. Device Programming ......................................................................................................................... 24 D.3.2. In –Person and Telephone Follow-up visits ...................................................................................... 26 D.4. Study Population: Inclusion and Exclusion Criteria ................................................................................. 27 D.4.1.Inclusion Criteria ................................................................................................................................ 28 D.4.2. Exclusion Criteria .............................................................................................................................. 28 D.4.3. Inclusion of women ........................................................................................................................... 29 D.5. Follow-up and Endpoints .......................................................................................................................... 29 D.6. Planned enrollment and randomization ..................................................................................................... 30 D.7 Timeline of the Study ................................................................................................................................. 30 D.8. Quality of Life........................................................................................................................................... 30 D.9. The 6-minute Walk Test (6MWT) ............................................................................................................ 30 D.10. Blood Samples ........................................................................................................................................ 30 D.11. TRIAL DESIGN; POWER, DURATION AND STATISTICAL ANALYSIS ...................................... 31 D.11.1. Endpoint Event Rates ...................................................................................................................... 31 D.11.2.Significance Level and Power .......................................................................................................... 31 D.11.3. Recruitment and Randomization ..................................................................................................... 31 D.11.4. Sequential stopping rule .................................................................................................................. 31 RAID Protocol Version 6.0 Page 2 of 47 September 5, 2014 Ranolazine in High Risk ICD Patients D.11.5. Trial Power and Duration@ .............................................................................................................. 33 D.11.6. Analysis ........................................................................................................................................... 33 D.11.7. Validation and Assumptions ............................................................................................................ 34 D.11.8. Sensitivity Analysis ......................................................................................................................... 34 D.11.9. Treatment Interactions ..................................................................................................................... 34 D.11.10.Technical Note ................................................................................................................................ 34 D.11.11. Secondary Analysis ....................................................................................................................... 35 D.12 ORGANIZATION AND KEY PERSONNEL ........................................................................................ 36 E. PROTECTION OF HUMAN PATIENTS ................................................................................................... 37 E.1. Ranolazine ................................................................................................................................................. 37 E.2. Risk to the Patients .................................................................................................................................... 37 E.2.1. Adverse Reactions: Clinical Trial Experience ................................................................................... 37 E.2.2. QT Prolongation ................................................................................................................................. 38 E.2.3. Drug-drug Interactions ....................................................................................................................... 38 E.3. Recruitment and Informed Consent ........................................................................................................... 39 E.4. Protection Against Risk ............................................................................................................................. 39 E.4.1. ECG monitoring ................................................................................................................................. 39 E.4.2. Drug interaction ................................................................................................................................. 39 E.4.3. Implantable Cardioverter Defibrillators ............................................................................................. 39 E.4.4. Privacy ............................................................................................................................................... 40 E.5. Data and Safety Monitoring Plan .............................................................................................................. 40 E.6. Adverse Drug Experience Reporting ........................................................................................................
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