Study Title: Multimodal Assessment to Optimise the Result of Percutaneous Coronary Interventions. Short title: The Oxford Optimisation of PCI Study (OXOPT-PCI study). Chief Investigator: Prof. Adrian Banning, Consultant Cardiologist 1 Investigators: Prof. Rajesh Kharbanda, Consultant Cardiologist 1 Dr. Jeremy Langrish, Consultant Cardiologist 1 Dr. Andrew Lucking, Consultant Cardiologist 1 Dr. Mathias Wolfrum, Interventional Research Fellow 1 Dr. Giovanni Luigi De Maria, Interventional Research Fellow 2 1 Oxford University Hospitals NHS Foundation Trust 2 University of Oxford Sponsor: Oxford University Hospitals NHS Foundation Trust Funder: Department of Cardiovascular Medicine Chief Investigator Signature/Date: No potential conflicts of interest to declare Confidentiality Statement This document contains confidential information that must not be disclosed to anyone other than the Sponsor, the Investigator Team, host organisation, and members of the Research Ethics Committee, unless authorised to do so. Subject: Research Protocol Ethics Ref/ IRAS number: 16/SC/0394/ 204681 Principal Investigator: Adrian Banning Version/Date: V1.2_14.09.2016 Short Title: OXOPT-PCI study Page: 1 of 31 TABLE OF CONTENTS 1. AMENDMENT HISTORY .................................................................................................. 4 2. KEY TRIAL CONTACTS ................................................................................................... 4 3. SYNOPSIS ........................................................................................................................ 4 4. ABBREVIATIONS ............................................................................................................. 6 5. BACKGROUND AND RATIONALE .................................................................................. 7 5.1 Post-PCI FFR as an indicator of clinical outcome ....................................................... 7 5.2 Causes of persistently low FFR after PCI ................................................................... 7 5.3 Assessment of coronary physiology (coronary pressure/flow) .................................... 8 5.4 Imaging Modalities Used to Evaluate Coronary Artery Disease ................................. 8 5.5 Background Summary ................................................................................................. 9 5.6 Study Hypothesis ........................................................................................................ 9 6. OBJECTIVES AND OUTCOME MEASURES/ENDPOINTS .......................................... 10 7. TRIAL DESIGN ............................................................................................................... 11 8. STUDY RISKS AND BENEFITS ..................................................................................... 12 8.1 Study risks ................................................................................................................. 12 8.1.1 Standard PCI procedure ......................................................................................... 12 8.1.2 Cardiac physiological measurements .................................................................... 13 8.1.3 Intravascular imaging ............................................................................................. 13 8.2 Study benefits ............................................................................................................ 13 9. PARTICIPANT IDENTIFICATION ................................................................................... 13 9.1 Study Participants ..................................................................................................... 13 9.2 Inclusion Criteria ........................................................................................................ 14 9.3 Exclusion Criteria ...................................................................................................... 14 10. STUDY PROCEDURES ................................................................................................ 15 10.1 Study timeline (see “Integrated flowchart for OXOPT-PCI study” as in Appendix 1) 15 10.2 Recruitment ............................................................................................................. 15 10.3 Consent ................................................................................................................... 15 10.3.1 Screening and Final Eligibility Assessment ............................................................ 15 10.3.2 Informed Consent ................................................................................................... 15 10.4 Baseline Visit ........................................................................................................... 16 10.5 Study visit - Intervention: Coronary angiogram and PCI ......................................... 16 10.5.1 Stage 1: Diagnostic Coronary Angiogram and FFR Assessment .......................... 18 Subject: Research Protocol Ethics Ref/ IRAS number: 16/SC/0394/ 204681 Principal Investigator: Adrian Banning Version/Date: V1.2_14.09.2016 Short Title: OXOPT-PCI study Page: 2 of 31 10.5.2 Stage 2: Stenting .................................................................................................... 18 10.5.3 Stage 3: Assessment and Optimisation of PCI Result ........................................... 18 10.5.4 Stage 4: Assessment of the PCI Optimisation ....................................................... 19 10.5.5 Stage 5: Optimisation of the PCI Result according to FFR/ End of Procedure ...... 19 10.6 Post PCI Assessment and Discharge Management ............................................... 20 10.7 Follow up visit - Telephone follow-up at 12 months ................................................ 21 10.8 Discontinuation/Withdrawal of Participants from Study ........................................... 21 10.9 Definition of End of Study ........................................................................................ 21 11. STUDY ASSESSMENTS ............................................................................................... 23 11.1 Clinical Data Collection ........................................................................................... 23 11.2 Analysis of cardiac physiological measurements .................................................... 23 11.3 Optical Coherence Tomography (OCT) .................................................................. 23 12. SAFETY Reporting ........................................................................................................ 23 12.1 Definitions of Serious Adverse Events .................................................................... 23 12.2 Reporting Procedures for Serious Adverse Events ................................................. 24 13. STATISTICS .................................................................................................................. 25 13.1 Number of Participants ............................................................................................ 25 13.2 Analysis of Endpoints .............................................................................................. 25 14. DATA MANAGEMENT ................................................................................................... 26 14.1 Access to Data ........................................................................................................ 26 14.2 Data Recording and Record Keeping ..................................................................... 26 15. Quality assurance procedures ....................................................................................... 26 16. ETHICAL AND REGULATORY CONSIDERATIONS .................................................... 26 16.1 Declaration of Helsinki ............................................................................................. 26 16.2 Guidelines for Good Clinical Practice ...................................................................... 27 16.3 Approvals ................................................................................................................ 27 16.4 Reporting ................................................................................................................. 27 16.5 Participant Confidentiality ........................................................................................ 27 17. Funding and INSURANCE ............................................................................................. 27 17.1 Funding ................................................................................................................... 27 17.2 Insurance ................................................................................................................. 27 18. PUBLICATION POLICY ................................................................................................. 28 19. REFERENCES .............................................................................................................. 29 20. Appendix ........................................................................................................................ 31 20.1 Appendix A: Integrated Flowchart for the OxOPT - PCI study ....................................... 31 Subject: Research Protocol Ethics Ref/ IRAS number: 16/SC/0394/ 204681 Principal Investigator: Adrian Banning Version/Date: V1.2_14.09.2016 Short Title: OXOPT-PCI study Page: 3 of 31 1. AMENDMENT HISTORY Previous