Coronary Artery DiseasePIONEER-IVNCT04923191
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
A study of Coronary Artery Disease, run by National University of Ireland, Galway, Ireland at 19 sites in 5 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,540 participants
- Where
- 19 sitesin 5 countries
- Study dates
- 12 Nov 2021to Jan 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
19 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
19 sites in 5 countries
Netherlands6 sites, 6 recruiting
- Recruiting
OLVG Amsterdam
Amsterdam
Giovanni Amoroso
- Recruiting
Medisch Spectrum Twente, Thoraxcentrum, Endchede
Enschede
Clemens Von Birgelen
- Recruiting
UMC Groningen
Groningen
Joanna Wykrzykowska, MD PhD
- Recruiting
Medisch Centrum Leeuwarden
Leeuwarden
Sjoerd Hofma
- Recruiting
Maasstad Ziekenhuis
Rotterdam
Valeria Paradies
- Recruiting
Den Haag Ziekenhuis
The Hague
Samer Somi
Belgium5 sites, 5 recruiting
- Recruiting
ASZ Aalst
Aalst
Liesbeth Rosseel, MD
- Recruiting
OLVZ Aalst
Aalst
Jeroen Sonck
- Recruiting
Imelda Ziekenhuis
Bonheiden
Kenneth De Wilder
- Recruiting
CHU Charleroi
Charleroi
Adel Aminian
- Recruiting
Jessa Hospital Hasselt
Hasselt
Edouard Benit
Spain4 sites, 4 recruiting
- Recruiting
Hospital Clínico de Barcelona
Barcelona
Manel Sabate
- Recruiting
Lucas Augusti Hospital
Lugo
Raymundo Ocaranza
- Recruiting
Hospital Clínico Universitario of Valladolid
Valladolid
Ignacio J Amat-Santos
- Recruiting
Hospital Álvaro Cunqueiro Vigo
Vigo
Victor Alfonso Jimenez Diaz
United Kingdom3 sites, 3 recruiting
- Recruiting
Barts Health NHS Trust, London
London
Andreas Baumbach, MD
- Recruiting
Freeman Hospital
Newcastle
Mohammad Alkhalil
- Recruiting
University Hospitals Southampton
Southampton
Nick Curzen
Ireland1 site, 1 recruiting
- Recruiting
University Hospital Galway
Galway
Faisal Sharif, MD
About this study
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
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.
- Conditions
- Coronary Artery Disease
- Being tested
- Angiography-derived physiology guidance/Local routine diagnostic procedure (LRDP) and usual care
- Keywords
- coronary artery disease, ischemia, quantitative flow ratio (QFR), P2Y12 monotherapy, drug-eluting stent, physiology guidance, angio-FFR, Coronary Angiography-derived FFR (caFFR)
- Medical subject headings
- Coronary Artery Disease, Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiography-derived physiology guidance/Local routine diagnostic procedure (LRDP) and usual careOther
percutaneous coronary intervention
| Study group | Role | What they receive |
|---|---|---|
| Angiography-derived Physiology Guidance: angio-FFR (QFR and caFFR) | Other | Quantitative Flow Ratio- QFR, Coronary angiography-derived FFR - caFFR Receives: Other: Angiography-derived physiology guidance/Local routine diagnostic procedure (LRDP) and usual care |
| Local routine diagnostic procedure (LRDP) and usual care | Other | Not described Receives: Other: Angiography-derived physiology guidance/Local routine diagnostic procedure (LRDP) and usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (7)
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
Measured: 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
Measured: 12, 24 and 36 months
Myocardial Infarction (MI)
Peri-procedure Myocardial Infarction according to 4th universal definition
Measured: 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)
Measured: index procedure
Stent Thrombosis
Definite, Probable, Definite or Probable
Measured: 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
Measured: 12, 24 and 36 months
Bleeding
Bleeding according to Bleeding Academic Research Consortium (BARC) (BARC 2, 3 and 5) classification
Measured: 12, 24 and 36 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2021
- Study start12 Nov 2021
- Primary completionJan 2026 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 2,540 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University of Ireland, Galway, Ireland
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Patrick Serruys, National University of Ireland, Galway, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04923191
- Sponsor's protocol ID
- NUIG-2021-001
- Acronym
- PIONEER-IV
- Status last verified
- Oct 2023
- First submitted
- 3 Jun 2021
- Last updated
- 30 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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;86:67-77. doi: 10.1016/j.carrev.2025.07.003. Epub 2025 Jul 8.
PubMed 40675853He 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.
PubMed 39395074Hara 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, Wijns W, Sharif F, Onuma Y; PIONEER IV trial investigator. Angiography-derived physiology guidance vs usual care in an All-comers PCI population treated with the healing-targeted supreme stent and Ticagrelor monotherapy: PIONEER IV trial design. Am Heart J. 2022 Apr;246:32-43. doi: 10.1016/j.ahj.2021.12.018. Epub 2022 Jan 3.
PubMed 34990582
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04923191
- Acronym / sponsor ID
- PIONEER-IV / NUIG-2021-001
- Conditions
- Coronary Artery Disease
- Keywords
- coronary artery disease, ischemia, quantitative flow ratio (QFR), P2Y12 monotherapy, drug-eluting stent, physiology guidance, angio-FFR, Coronary Angiography-derived FFR (caFFR)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,540 participants (estimated)
- Lead sponsor
- National University of Ireland, Galway, IrelandUniversity, hospital or other
- Study start
- 12 Nov 2021 (actual)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 11 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Angiography-derived Physiology Guidance: angio-FFR (QFR and caFFR) | Other | Other: Angiography-derived physiology guidance/Local routine diagnostic procedure (LRDP) and usual careQuantitative Flow Ratio- QFR, Coronary angiography-derived FFR - caFFR |
| Local routine diagnostic procedure (LRDP) and usual care | Other | Other: Angiography-derived physiology guidance/Local routine diagnostic procedure (LRDP) and usual care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angiography-derived physiology guidance/Local routine diagnostic procedure (LRDP) and usual carepercutaneous coronary intervention | Other | Angiography-derived Physiology Guidance: angio-FFR (QFR and caFFR), Local routine diagnostic procedure (LRDP) and usual care |
Primary outcome
Patient-oriented Composite Endpoint (PoCE)
Time frame: 12 months
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.
7 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2023.
- Derived from this study: PubMed 40675853Renkens 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;86:67-77. doi: 10.1016/j.carrev.2025.07.003. Epub 2025 Jul 8.
- Derived from this study: PubMed 39395074He 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.
- Derived from this study: PubMed 34990582Hara 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, Wijns W, Sharif F, Onuma Y; PIONEER IV trial investigator. Angiography-derived physiology guidance vs usual care in an All-comers PCI population treated with the healing-targeted supreme stent and Ticagrelor monotherapy: PIONEER IV trial design. Am Heart J. 2022 Apr;246:32-43. doi: 10.1016/j.ahj.2021.12.018. Epub 2022 Jan 3.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
19 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Coronary Artery Disease, run by National University of Ireland, Galway, Ireland at 19 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Netherlands, Belgium, Spain, United Kingdom, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Patrick W Serruys, MD (+31622924061, Patrick.Serruys@universityofgalway.ie), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient-oriented Composite Endpoint (PoCE) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04923191, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2023.