The Cardiovascular Inflammation Reduction Trial (CIRT) Investigator and Coordinator Teleconference November 22, 2013 Erin Cunniff CIRT Project Coordinator Aruna Pradhan, MD, MPH Assistant Professor of Medicine, HMS Director, Preventive Medicine Cohorts Biorepository, BWH

Agenda for Call Recruitment Overview – Aruna Pradhan, MD Protocol Amendments – Aruna Pradhan, MD Site Management – Erin Cunniff Q and A

Recruitment Overview Sites Participants 368 Interested 274 with IRB approval 245 ready to screen 130 with 1+ participants screened 63 with 1+ participants randomized Participants 654 Screened 212 Randomized (as of November 21, 2013)

Protocol Amendments Qualifying Event has been expanded to include multivessel coronary disease Qualifying white blood cell count (WBC) threshold has been lowered to 3,500

Qualifying Event: Current Documented myocardial infarction within the past five years The qualifying prior myocardial infarction must be documented either by hospital records OR by evidence on current ECG of Q waves in two contiguous leads AND/OR imaging test demonstrating wall motion abnormality or scar The patient must also have completed any planned coronary revascularization procedures associated with the qualifying event, and be clinically stable for at least 60 days prior to screening.

Qualifying Event: New Eligibility Criteria Documented myocardial infarction within the past five years OR evidence of multivessel coronary artery disease by angiography in the past 5 years.

Additional Eligibility Criteria Evidence of multivessel coronary artery disease by angiography in the past 5 years. To qualify on the basis of multivessel coronary disease, there must be angiographic evidence within the past 5 years of atherosclerosis in at least 2 major epicardial vessels defined either as the presence of a stent, a coronary bypass graft, or an angiographic lesion of 60% or greater. Left main coronary artery disease that has been revascularized with a stent or bypass graft will qualify as multivessel disease, as will the presence of a 50% or greater isolated left main stenosis

Qualifying Event Which qualifying event is preferred in completing V1 eligibility criteria? Myocardial Infarction If the patient had an MI within 5 years, please collect and forward that documentation The date of index event should be the date of MI Multivessel coronary disease If the patient has NOT had an MI within 5 years The date of index event should be the date of the angiogram that demonstrated multivessel CAD

What documentation is required? Myocardial infarction Hospital discharge record EKG with Q waves Echo with scar or clear wall motion abnormality Nuclear stress test showing scar or wall motion abnormality Angiographic evidence of multivessel CAD Cardiac catheterization report Operative report (PCI or CABG) Not Accepted: Coronary CTA

Protocol Change #2 Exclusion criteria NEW WBC exclusion criteria Previously: WBC < 4,000/μL NEW WBC exclusion criteria WBC < 3,500/μL

Protocol Amendments Protocol Amendment BWH IRB CCC DSMB Copernicus Local IRBs IRB Services EDC System Recruitment Materials Manual of Operations Quick Reference Card

Protocol Amendments Protocol Amendment BWH IRB CCC DSMB Copernicus Local IRBs IRB Services EDC System Recruitment Materials Manual of Operations Quick Reference Card

Protocol Amendments Protocol Amendment BWH IRB CCC DSMB Copernicus Local IRBs IRB Services EDC System Recruitment Materials Manual of Operations Quick Reference Card

Protocol Amendments Protocol Amendment BWH IRB CCC DSMB Copernicus Local IRBs IRB Services EDC System Recruitment Materials Manual of Operations Quick Reference Card

Protocol Amendments Protocol Amendment BWH IRB CCC DSMB Next Steps Copernicus Local IRBs IRB Services EDC System Recruitment Materials Manual of Operations Quick Reference Card

Agenda for Call Recruitment Overview – Aruna Pradhan, MD Protocol Amendments – Aruna Pradhan, MD Study Drug Management – Erin Cunniff Q and A

Study Drug Resupply Study drug will expire in March 2014 - new drug shipments have been initiated to all sites Shipments are being processed in 2 phases Email notifications are sent to sites before each shipment is sent Fax the study drug acknowledgement form to BOTH the CIRT CC and Catalent CIRT CC: 855-605-6326 Catalent: 866-600-0029

Study Drug Acknowledgement

Study Drug Resupply Return all study drug once new drug is received Include Drug Shipment Return form in the box with the returned drug The form can be found on theCIRT.org in Study Site Information in the CIRT Coordinating Center Forms section (PWD: CIRT2013)

Study Drug Resupply

Study Drug Resupply Return all study drug once new drug is received Include Drug Shipment Return form in the box with the returned drug The form can be found on theCIRT.org in Study Site Information in the CIRT Coordinating Center Forms section (PWD: CIRT2013) Email: GMB-DC-KCMReturns@catalent.com to obtain a FedEx label

Study Drug Resupply

Study Drug Resupply Return all study drug once new drug is received Include Drug Shipment Return form in the box with the returned drug The form can be found on theCIRT.org in Study Site Information in the CIRT Coordinating Center Forms section (PWD: CIRT2013) Email: GMB-DC-KCMReturns@catalent.com to obtain a FedEx label Do not reissue unused calendar packs from old supply

Agenda for Call Recruitment Overview – Aruna Pradhan, MD Protocol Amendments – Aruna Pradhan, MD Site Management – Erin Cunniff Q and A

Q & A How do I assess my patient’s New York Heart Association (NYHA) heart failure class? On the EDC page click the “help” link in the top right, which will give you the definition for each class of heart failure Class I: No limitation of physical activity Class II: Slight limitation of physical activity. Comfortable at rest but ordinary activity causes fatigue, shortness of breath Class III: Marked limitation of physical activity. Comfortable at rest but less than ordinary activity causes fatigue or dyspnea Class IV: Symptoms at rest. Unable to do any physical activity without worsening symptoms

Q & A Do I have to do the EKG at V4? Do I have to do the ABI? What if my patient already takes folic acid? Do I distribute randomized drug in the same way I distribute run-in calendar packs? What if a patient arrives for a visit and the CRF has not appeared in the EDC yet?