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

Official title

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

Overview

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.

Interventions

• Other Angiography-derived physiology guidance/Local routine diagnostic procedure (LRDP) and usual care
  percutaneous coronary intervention

Primary outcome measures

• Patient-oriented Composite Endpoint (PoCE) [Time frame: 12 months]

Secondary outcome measures (7)

• Vessel-oriented composite endpoints (VoCE) [Time frame: 12, 24 and 36 months]
• Device-oriented composite endpoint (DoCE) [Time frame: 12, 24 and 36 months]
• Myocardial Infarction (MI) [Time frame: 48 hours post-procedure]
• Device Success Rate [Time frame: index procedure]
• Stent Thrombosis [Time frame: Procedure, 12, 24 and 36 months]
• Target Vessel Failure (TVF) [Time frame: 12, 24 and 36 months]
• Bleeding [Time frame: 12, 24 and 36 months follow-up]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Netherlands · 6 centers

• OLVG Amsterdam — Amsterdam
• Medisch Spectrum Twente, Thoraxcentrum, Endchede — Enschede
• UMC Groningen — Groningen
• Medisch Centrum Leeuwarden — Leeuwarden
• Maasstad Ziekenhuis — Rotterdam
• Den Haag Ziekenhuis — The Hague

Belgium · 5 centers

• ASZ Aalst — Aalst
• OLVZ Aalst — Aalst
• Imelda Ziekenhuis — Bonheiden
• CHU Charleroi — Charleroi
• Jessa Hospital Hasselt — Hasselt

Spain · 4 centers

• Hospital Clínico de Barcelona — Barcelona
• Lucas Augusti Hospital — Lugo
• Hospital Clínico Universitario of Valladolid — Valladolid
• Hospital Álvaro Cunqueiro Vigo — Vigo

United Kingdom · 3 centers

• Barts Health NHS Trust, London — London
• Freeman Hospital — Newcastle
• University Hospitals Southampton — Southampton

Ireland · 1 center

• University Hospital Galway — Galway

Publications

• Renkens MPL, Tsai TY, Revaiah PC, Kageyama S, Reiber JHC, de Winter RJ, Grundeken M, Nurmohamed NS, Stroes E, Garg S, von Birgelen C, Hofma S, Alkhalil M, Rosseel L, Sharif F, Smits PC, Baumbach A, Onuma Y, Wykrzykowska JJ, Serruys PW. Impact of elevated lipoprotein(a) on epicardial coronary flow conductance and endoluminal atherosclerotic disease distribution. Cardiovasc Revasc Med. 2026 May;86:6 PMID 40675853
• He X, Tsung-Ying T, Revaiah PC, Wykrzykowska JJ, Rosseel L, Sharif F, Muramatsu T, Reiber JH, Garg S, Miyashita K, Tobe A, Tao L, Onuma Y, Serruys PW. Nomogram based on virtual hyperemic pullback pressure gradients for predicting the suboptimal post-PCI QFR outcome after stent implantation. Int J Cardiovasc Imaging. 2024 Dec;40(12):2469-2479. doi: 10.1007/s10554-024-03253-1. Epub 2024 Oct 12. PMID 39395074
• Hara H, Serruys PW, O'Leary N, Gao C, Murray A, Breslin E, Garg S, Bureau C, Reiber JH, Barbato E, Aminian A, Janssens L, Rosseel L, Benit E, Campo G, Guiducci V, Casella G, Santarelli A, Franze A, Diaz VAJ, Iniguez A, Brugaletta S, Sabate M, Amat-Santos IJ, Amoroso G, Wykrzykowska J, von Birgelen C, Somi S, Liu T, Hofma SH, Curzen N, Trillo R, Ocaranza R, Mathur A, Smits PC, Escaned J, Baumbach A PMID 34990582

Identifiers

NCT: NCT04923191 · NUIG-2021-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗