The PIONEER-IV Study is Comparing Clinical Outcomes Between Angiography-derived Physiology Guidance to Usual Care in an All-comers PCI Population With Unrestrictive Use of the HT Supreme Sirolimus-eluting Stent

Study Overview
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Brief Summary
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PIONEER-IV is a prospective, single-blind (patient), randomized, 1:1, controlled, multi-center study comparing clinical outcomes between angiography-derived physiology guidance to LRDP and usual care in an all-comers patient population (including patients with high bleeding risk, HBR) undergoing PCI with unrestrictive use of the HT Supreme sirolimus-eluting stent. Patients will be randomized to either angio-based physiology guidance angio-FFR (Quantitative Flow Ratio and coronary angiography-derived FFR, caFFR) or local routine diagnostic procedure (LRDP) and usual care. Patients will be treated with 1-year P2Y12 inhibitor monotherapy after 1-month of dual-antiplatelet therapy in approximately 2540 (2*1270) patients. All patients (both cohorts) must receive dual anti-platelet therapy, being aspirin (ASA) and ticagrelor for 1 month, followed by 11 months of ticagrelor only (i.e. monotherapy). At 1 year, ticagrelor monotherapy is replaced by aspirin monotherapy or left to the discretion of the operator.

Official Title
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Non-inferiority of Angiography-derived Physiology Guidance Versus Usual Care in an All-comers PCI Population Treated With Unrestricted Use of the Healing-Targeted Supreme (HT Supreme) Drug-eluting Stent and P2Y12 Inhibitor Monotherapy After 1-month of Dual-antiplatelet Therapy

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Other: Angiography-derived physiology guidance/Local routine diagnostic procedure (LRDP) and usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has chronic stable angina, acute coronary syndromes or silent ischemia; Presence of one or more coronary artery stenoses of ≥50% (by visual assessment) in a native coronary artery (with or without prior stent/other device treatment) or in a saphenous venous or arterial bypass conduit suitable for coronary stent implantation; The vessel should have a reference vessel diameter of at least 2.25 mm by visual assessment (no limitation on the number of treated lesions, vessels, or lesion length); Patient has been informed of the nature of the study and agrees to its provisions and has provided written informed consent as approved by the Ethical Committee and is willing to comply with all protocol-required (follow-up) evaluations. Exclusion Criteria: Patient is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential according to local practice); Known intolerance to cobalt chromium, and medications such as sirolimus, aspirin, heparin, bivalirudin or P2Y12 inhibitors; Planned major elective surgery requiring discontinuation of (dual)anti platelet therapy (DAPT) within 12 months of procedure; Concurrent medical condition with a life expectancy of less than 3 years; Currently participating in another trial and not yet at its primary endpoint; Active pathological bleeding; History of intracranial haemorrhage.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Angiography-derived Physiology Guidance: angio-FFR (QFR and caFFR)<br>Quantitative Flow Ratio- QFR, Coronary angiography-derived FFR - caFFR | Other: Angiography-derived physiology guidance/Local routine diagnostic procedure (LRDP) and usual care<br>* percutaneous coronary intervention<br>|
| Other: Local routine diagnostic procedure (LRDP) and usual care<br> | Other: Angiography-derived physiology guidance/Local routine diagnostic procedure (LRDP) and usual care<br>* percutaneous coronary intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-oriented Composite Endpoint (PoCE) | PoCE is a composite clinical endpoint of: all-cause death; any stroke, Modified Rankin scale, (MRS ≥1); any myocardial infarction; any clinically and physiologically driven revascularization. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vessel-oriented composite endpoints (VoCE) | VoCE is a composite clinical endpoint of: Vessel-related cardiovascular Death Target-vessel related MI Clinically and physiologically-oriented Target vessel revascularization | 12, 24 and 36 months | 
| Device-oriented composite endpoint (DoCE) | DoCE is a composite endpoint of: Cardiovascular Death Target-vessel related MI Clinically and physiologically-oriented Target lesion revascularization | 12, 24 and 36 months | 
| Myocardial Infarction (MI) | Peri-procedure Myocardial Infarction according to 4th universal definition | 48 hours post-procedure | 
| Device Success Rate | according to the statement from European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the European Society of Cardiology (ESC) | index procedure | 
| Stent Thrombosis | Definite, Probable, Definite or Probable | Procedure, 12, 24 and 36 months | 
| Target Vessel Failure (TVF) | TVF is a composite of: Cardiovascular Death Target-vessel related MI Clinically and physiologically-oriented Target vessel revascularization | 12, 24 and 36 months | 
| Bleeding | Bleeding according to Bleeding Academic Research Consortium (BARC) (BARC 2, 3 and 5) classification | 12, 24 and 36 months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary artery disease, ischemia, quantitative flow ratio (QFR), P2Y12 monotherapy, drug-eluting stent, physiology guidance, angio-FFR, Coronary Angiography-derived FFR (caFFR)