Coronary Artery DiseasePhase 4PARTHENOPENCT04135989
Personalized Vs. Standard Duration of Dual Antiplatelet Therapy and New-generation Polymer-Free vs- Biodegradable-Polymer DES
A Phase 4 study testing Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease., Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease. and Personalized DAPT duration in people with Coronary Artery Disease and Acute Coronary Syndrome, run by Federico II University at 13 sites in Italy.
Trial summary
New-generation metallic drug-eluting stents represent the standard of care among patients undergoing percutaneous coronary intervention (PCI). Currently, few data are available as regards to the safety and efficacy of the Cre8 amphilimus-eluting stent (Cre8 AES, Alvimedica, Instanbul, Turkey) in comparison with the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Acute Coronary Syndrome, Chronic Coronary Syndrome
- What is being tested?
- Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease., Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease. and Personalized DAPT duration
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,106 participants
- Where
- 13 sitesItaly
- Study dates
- 1 Jan 2020to 24 Oct 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Age ≥18 years;
- Clinical evidence of coronary artery disease requiring PCI with DES implantation;
- Any coronary lesion sized 2.25-4.5 mm by visual estimation.
Who cannot join
- Inability to provide informed consent;
- Active bleeding requiring medical attention (BARC ≥2);
- Need for chronic oral anticoagulant therapy;
- Planned surgery within 3 months;
- Known hypersensitivity or allergy to aspirin or any P2Y12 receptor inhibitor (clopidogrel, prasugrel, ticagrelor), heparin, contrast agent, or any DES-components;
- Previous treatment with bioresorbable vascular scaffolds;
Show all 10Show fewer
- Participation in another study that has not reached the primary endpoint;
- A life expectancy of less than 24 months;
- Female of childbearing potential;
- Under judicial protection, tutorship or curatorship.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Italy13 sites
Casa di Cura Villa Dei Fiori
Acerra, Naples, 80011
A.O.R.N. S.Giuseppe Moscati-Città Ospedaliera
Avellino, 83100
Ospedale San Giuseppe Moscati
Aversa, 81031
A.O.R.N. Sant'Anna e San Sebastiano
Caserta, 81100
Ospedale "Maria SS. Addolorata"
Eboli, SA, 84025
Ospedale San Giuliano
Giugliano in Campania, 80014
A.O.R.N. A. Cardarelli
Naples, 80131
Federico II University of Naples
Naples, 80131
Ospedale San Giovanni Bosco - ASL Napoli 1
Naples, 80131
Ospedale del Mare
Naples, 80147
Ospedale Santa Maria della Pietà
Nola, 80035
Ospedale S.Maria delle Grazie
Pozzuoli, Naples, 80078
AOU San Giovanni di Dio e Ruggi d'Aragona
Salerno, 84131
About this study
Official title: Randomized 2x2 Factorial Trial Comparing the Cre8 Amphilimus-sirolimus Eluting Stent vs. the Synergy Everolimus-eluting Stent and a Personalized vs. Standard Duration of Dual Antiplatelet Therapy in All-comers Patients Undergoing Percutaneous Coronary Intervention
New-generation metallic drug-eluting stents represent the standard of care among patients undergoing percutaneous coronary intervention (PCI). Currently, few data are available as regards to the safety and efficacy of the Cre8 amphilimus-eluting stent (Cre8 AES, Alvimedica, Instanbul, Turkey) in comparison with the biodegradable polymer everolimus-eluting stent (Synergy EES, Boston Scientific, Marlborough, MA, USA). Results from randomized trials and meta-analyses consistently indicate that prolonged dual antiplatelet therapy (DAPT) after PCI reduces ischemic events, but invariably conveys an excess of clinically relevant bleeding, which is proportional to the duration of treatment. It has been estimated, indeed, that for every non-fatal ischemic event avoided with prolonged DAPT, two or more clinically relevant bleeding events have to be expected. Given the trade-off between benefits and risks and the lack of mortality benefit in favor of prolonged DAPT, expert consensus suggests that DAPT duration should be individualized based on ischemic versus bleeding risks. At this regard, the DAPT score has been recently proposed as standardized tool to identify patients who derive benefit or lack from a prolonged course of DAPT. However, a prospective assessment of the DAPT score is lacking and whether a personalized duration of DAPT based on the DAPT score improves the net clinical benefit remains unknown.
The objective of the study is to compared the safety and the efficacy of the Cre8 AES with the Synergy EES and a personalized DAPT duration based on the DAPT score with a standard DAPT duration among patients undergoing PCI.
Read the detailed description
The objective of the trial is:
- to evaluate the efficacy and safety of the Cre8 AES vs. the Synergy EES in a broadly unselected patient population with coronary artery disease undergoing PCI; ii) to compare the safety and efficacy of a personalized DAPT duration (3-, 6-, or 24-month) guided by the application of the DAPT score with a standard DAPT duration (12-month) after PCI.
In particular, the objectives of the trial are to test the following hypothesis:
- The Cre8 AES is non-inferior to the Synergy EES with regards to a device-oriented composite endpoint (DOCE) at 1-year follow-up.
- A personalized DAPT duration based on the DAPT score is superior to a standard DAPT duration with regards to a net adverse clinical endpoint (NACE) at 2-year follow-up.
This is a prospective, randomized, multicenter, investigator-initiated, assessor-blind trial to be conducted at interventional cardiology centers in Italy. Patients undergoing PCI will be randomized in a 2-by-2 randomization fashion to undergo PCI with the Cre8 AES or Synergy EES and to receive a personalized or standard DAPT duration. All patients will be followed at 3-, 6-, 12- and 24-month after PCI for clinical endpoints.
Use of experimental and control DES:
Both the study stent (Cre8 AES) and the control stent (Synergy EES) will be used according to their indications for use. The randomly assigned stent is not expected to have an influence on the conduct of the procedure that will take place according to the routine practice. Eligible patients will undergo PCI as per local protocol, according to current guidelines of the European Society of Cardiology on myocardial revascularization. The technique of PCI (vascular access route, choice of the vascular sheath diameter, choice of the diagnostic and guiding catheters sizes and shapes, choice of the coronary guidewire) will be left to the discretion of the operator as per standard individual and local practice. The operator will choose the appropriate length and diameter of the stents to be implanted by visual estimate or quantitative coronary angiography as per local practice. The Cre8 AES and the Synergy EES systems are commercially available and all sizes may be used for the study.
DAPT duration according to randomization:
DAPT duration in patients randomized to personalized DAPT regimen: In patients that are randomized to a personalized DAPT and have a low DAPT score (<2), DAPT duration is recommended for 3 months in case of stable coronary artery disease at the time of the index procedure or for 6 months in case of acute coronary syndrome at the time of the index procedure. A low dose of aspirin (75 to 162 mg daily) will be administered throughout the course of the study. In patients that are randomized to a personalized DAPT and have a high DAPT score (≥2), DAPT duration is recommended for 24 months. Changes in the dose or in the type of P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) are allowed during the course of the study. A low dose of aspirin (75 to 162 mg daily) will be administered throughout the course of the study. At 12-month, patients on treatment with prasugrel or ticagrelor should continue the same P2Y12 receptor inhibitor. In this specific scenario, it is preferable to continue with the same P2Y12 receptor inhibitor (prasugrel 10 mg daily or ticagrelor 90 mg daily) or to switch to a low-dose regimen of ticagrelor (60 mg twice daily) if clinically indicated or to switch to clopidogrel (75 mg daily).
DAPT regimen in patients in patients randomized to a standard DAPT duration: In patients that are randomized to a standard DAPT duration, oral P2Y12 inhibitors (clopidogrel, prasugrel, or ticagrelor) should be administered for 12-month. A low dose of aspirin (75 to 162 mg daily) will be administered throughout the course of the study.
- Conditions
- Coronary Artery Disease, Acute Coronary Syndrome, Chronic Coronary Syndrome, Myocardial Infarction
- Being tested
- Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease., Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease., Personalized DAPT duration, Standard DAPT duration
- Medical subject headings
- Coronary Artery Disease, Acute Coronary Syndrome, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease.Device
Also called Cre8 AES
Implantation of polymer-free, amphilimus-eluting, drug-eluting stents
Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease.Device
Also called Synergy EES
Implantation of biodegradable-polymer, everolimus-eluting, drug-eluting stents
Personalized DAPT durationDrug
Duration of dual antiplatelet therapy according to DAPT score for 3- or 6- months in patients with low DAPT score (stable CAD or ACS, respectively) or for 24-months in patients with high DAPT score
Standard DAPT durationDrug
Duration of dual antiplatelet therapy for 12 months.
| Study group | Role | What they receive |
|---|---|---|
| Cre8 AES and personalized DAPT duration | Other | Percutaneous coronary intervention with implantation of a Cre8 amphilimus- eluting stent for coronary artery disease.
Personalized duration of dual antiplatelet therapy for 3-, 6-, or 24-month after percutaneous coronary intervention based on the DAPT score. Receives: Device: Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease.; Drug: Personalized DAPT duration |
| Cre8 AES and standard DAPT duration | Other | Percutaneous coronary intervention with implantation of a Cre8 amphilimus- eluting stent for coronary artery disease.
Standard duration of dual antiplatelet therapy for 12-month after percutaneous coronary intervention. Receives: Device: Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease.; Drug: Standard DAPT duration |
| Synergy EES and personalized DAPT duration | Other | Percutaneous coronary intervention with implantation of a Synergy everolimus-eluting stent for coronary artery disease.
Personalized duration of dual antiplatelet therapy for 3-, 6-, or 24-month after percutaneous coronary intervention based on the DAPT score. Receives: Device: Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease.; Drug: Personalized DAPT duration |
| Synergy EES and standard DAPT duration | Other | Percutaneous coronary intervention with implantation of a Synergy everolimus-eluting stent for coronary artery disease.
Standard duration of dual antiplatelet therapy for 12-month after percutaneous coronary intervention. Receives: Device: Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease.; Drug: Standard DAPT duration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Device-oriented composite endpoint (DOCE) for the comparison between the Cre8 AES and the Synergy EES.
The composite of cardiovascular death, myocardial infarction not clearly attributable to a non-target vessel, or clinically-driven target-lesion revascularization.
Measured: 12 months
Number of Participants with Net adverse clinical endpoint (NACE) for the comparison between a personalized and standard DAPT duration.
The composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or BARC type 2 to 5 bleeding at 24-month follow-up.
Measured: 24 months
Secondary outcomes (14)
Number of Participants with All-cause death
Measured: 12- and 24-month
Number of Participants with Death from cardiovascular causes
Measured: 12- and 24-month
Number of Participants with Myocardial infarction
Measured: 12- and 24-month
Number of Participants with Stroke
Measured: 12- and 24-month
Number of Participants with Clinically-driven target-lesion revascularization
Measured: 12- and 24-month
Number of Participants with Definite or probable stent thrombosis
Measured: 12- and 24-month
Number of Participants with Definite stent thrombosis
Measured: 12- and 24-month
Number of Participants with Any revascularization
Measured: 12- and 24-month
Number of Participants with Clinically-driven target-vessel revascularization
Measured: 12- and 24-month
Number of Participants with Urgent target-vessel revascularization
Measured: 12- and 24-month
Number of Participants with Urgent non-target-vessel revascularization
Measured: 12- and 24-month
Number of Participants with Any target-lesion revascularization
Measured: 12- and 24-month
Number of Participants with Any target-vessel revascularization
Measured: 12- and 24-month
Number of Participants with Bleeding events
Bleeding events according to the BARC, TIMI and GUSTO classification
Measured: 12- and 24-month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2019
- Study start1 Jan 2020
- Primary completion24 Oct 2021
- Study completion24 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Federico II UniversityThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- 2-by-2 randomization
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2,106 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federico II University
- Sponsor type
- University, hospital or other
- Collaborators
- AdvicePharma Group
- Responsible party
- Principal investigator, Giovanni Esposito, Federico II University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04135989
- Sponsor's protocol ID
- 197/19
- Acronym
- PARTHENOPE
- Status last verified
- Feb 2024
- First submitted
- 21 Oct 2019
- Last updated
- 23 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Piccolo R, Windecker S. Dual Antiplatelet Therapy in Percutaneous Coronary Intervention: A Tale of 2 Decades With New Perspectives in the Era of New-Generation Drug-Eluting Stents. Circ Cardiovasc Interv. 2016 Feb;9(2):e003587. doi: 10.1161/CIRCINTERVENTIONS.116.003587. No abstract available.
PubMed 26858081Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Juni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN; ESC Scientific Document Group; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018 Jan 14;39(3):213-260. doi: 10.1093/eurheartj/ehx419. No abstract available.
PubMed 28886622Spencer FA, Prasad M, Vandvik PO, Chetan D, Zhou Q, Guyatt G. Longer- Versus Shorter-Duration Dual-Antiplatelet Therapy After Drug-Eluting Stent Placement: A Systematic Review and Meta-analysis. Ann Intern Med. 2015 Jul 21;163(2):118-26. doi: 10.7326/M15-0083.
PubMed 26005909Bittl JA, Baber U, Bradley SM, Wijeysundera DN. Duration of Dual Antiplatelet Therapy: A Systematic Review for the 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Sep 6;68(10):1116-39. doi: 10.1016/j.jacc.2016.03.512. Epub 2016 Mar 29.
PubMed 27036919Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC Jr. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Sep 6;68(10):1082-115. doi: 10.1016/j.jacc.2016.03.513. Epub 2016 Mar 29. No abstract available.
PubMed 27036918Raber L, Piccolo R. CardioPulse: Different bleeding scores and which one should we use? Eur Heart J. 2016 Jan 21;37(4):327-31. No abstract available.
PubMed 27462674Yeh RW, Secemsky EA, Kereiakes DJ, Normand SL, Gershlick AH, Cohen DJ, Spertus JA, Steg PG, Cutlip DE, Rinaldi MJ, Camenzind E, Wijns W, Apruzzese PK, Song Y, Massaro JM, Mauri L; DAPT Study Investigators. Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention. JAMA. 2016 Apr 26;315(16):1735-49. doi: 10.1001/jama.2016.3775.
PubMed 27022822Piccolo R, Gargiulo G, Franzone A, Santucci A, Ariotti S, Baldo A, Tumscitz C, Moschovitis A, Windecker S, Valgimigli M. Use of the Dual-Antiplatelet Therapy Score to Guide Treatment Duration After Percutaneous Coronary Intervention. Ann Intern Med. 2017 Jul 4;167(1):17-25. doi: 10.7326/M16-2389. Epub 2017 Jun 13.
PubMed 28605779Rozemeijer R, Stein M, Voskuil M, van den Bor R, Frambach P, Pereira B, Koudstaal S, Leenders GE, Timmers L, Rittersma SZ, Kraaijeveld AO, Agostoni P, Roes KC, Doevendans PA, Stella PR; ReCre8 Study Investigators. Randomized All-Comers Evaluation of a Permanent Polymer Zotarolimus-Eluting Stent Versus a Polymer-Free Amphilimus-Eluting Stent. Circulation. 2019 Jan 2;139(1):67-77. doi: 10.1161/CIRCULATIONAHA.118.037707.
PubMed 30586704Navarese EP, Andreotti F, Schulze V, Kolodziejczak M, Buffon A, Brouwer M, Costa F, Kowalewski M, Parati G, Lip GY, Kelm M, Valgimigli M. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials. BMJ. 2015 Apr 16;350:h1618. doi: 10.1136/bmj.h1618.
PubMed 25883067Garcia-Garcia HM, McFadden EP, Farb A, Mehran R, Stone GW, Spertus J, Onuma Y, Morel MA, van Es GA, Zuckerman B, Fearon WF, Taggart D, Kappetein AP, Krucoff MW, Vranckx P, Windecker S, Cutlip D, Serruys PW; Academic Research Consortium. Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document. Circulation. 2018 Jun 12;137(24):2635-2650. doi: 10.1161/CIRCULATIONAHA.117.029289.
PubMed 29891620Piccolo R, Calabro P, Carrara G, Simonetti F, Varricchio A, Attisano T, Napolitano G, De Simone C, Carpinella G, Stabile E, Cirillo P, Di Serafino L, Caiazzo G, Tesorio T, Boccalatte M, Tuccillo B, Avvedimento M, Leone A, Galasso G, Cesaro A, Perrotta R, Niglio T, Castiello DS, Immobile Molaro M, Bardi L, Spinelli A, Cristiano S, Bellino M, Leonardi S, Biscaglia S, Costa F, Cassese S, McFadden E, Heg D, Stefanini GG, Franzone A, Capodanno D, Esposito G; PARTHENOPE Study Group. Personalized or Standard Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: The PARTHENOPE Randomized Trial. J Am Coll Cardiol. 2025 Dec 9;86(23):2352-2367. doi: 10.1016/j.jacc.2025.08.040. Epub 2025 Aug 30.
PubMed 40892607Piccolo R, Calabro P, Carrara G, Varricchio A, Baldi C, Napolitano G, De Simone C, Mauro C, Stabile E, Caiazzo G, Tesorio T, Boccalatte M, Tuccillo B, Cirillo P, Di Serafino L, Simonetti F, Leone A, Angellotti D, Bottiglieri G, Russolillo E, Galasso G, Perrotta R, Cesaro A, Niglio T, Capasso M, Spinelli A, Cristiano S, Faretra A, Bruzzese D, Chieffo A, Tarantini G, Leonardi S, Biscaglia S, Costa F, Cassese S, McFadden E, Heg D, Franzone A, Stefanini GG, Capodanno D, Esposito G, Parthenope Investigators FT. Polymer-free versus biodegradable-polymer drug-eluting stent in patients undergoing percutaneous coronary intervention: an assessor-blind, non-inferiority, randomised controlled trial. EuroIntervention. 2025 Jan 6;21(1):58-72. doi: 10.4244/EIJ-D-24-00657.
PubMed 39773824Piccolo R, Calabro P, Varricchio A, Baldi C, Napolitano G, De Simone C, Mauro C, Stabile E, Caiazzo G, Tesorio T, Boccalatte M, Tuccillo B, Bottiglieri G, Russolillo E, Di Lorenzo E, Carrara G, Cassese S, Leonardi S, Biscaglia S, Costa F, McFadden E, Heg D, Franzone A, Stefanini GG, Capodanno D, Esposito G. Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI. Am Heart J. 2023 Nov;265:153-160. doi: 10.1016/j.ahj.2023.08.001. Epub 2023 Aug 10.
PubMed 37572785
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized 2x2 Factorial Trial Comparing the Cre8 Amphilimus-sirolimus Eluting Stent vs. the Synergy Everolimus-eluting Stent and a Personalized vs. Standard Duration of Dual Antiplatelet Therapy in All-comers Patients Undergoing Percutaneous Coronary Intervention
- ClinicalTrials.gov ID
- NCT04135989
- Acronym / sponsor ID
- PARTHENOPE / 197/19
- Conditions
- Coronary Artery Disease, Acute Coronary Syndrome, Chronic Coronary Syndrome, Myocardial Infarction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,106 participants (estimated)
- Lead sponsor
- Federico II UniversityUniversity, hospital or other
- Collaborators
- AdvicePharma Group
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 24 Oct 2021 (actual)
- Study completion
- 24 Oct 2024 (estimated)
- First posted
- 23 Oct 2019 (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.
New-generation metallic drug-eluting stents represent the standard of care among patients undergoing percutaneous coronary intervention (PCI). Currently, few data are available as regards to the safety and efficacy of the Cre8 amphilimus-eluting stent (Cre8 AES, Alvimedica, Instanbul, Turkey) in comparison with the biodegradable polymer everolimus-eluting stent (Synergy EES, Boston Scientific, Marlborough, MA, USA). Results from randomized trials and meta-analyses consistently indicate that prolonged dual antiplatelet therapy (DAPT) after PCI reduces ischemic events, but invariably conveys an excess of clinically relevant bleeding, which is proportional to the duration of treatment. It has been estimated, indeed, that for every non-fatal ischemic event avoided with prolonged DAPT, two or more clinically relevant bleeding events have to be expected. Given the trade-off between benefits and risks and the lack of mortality benefit in favor of prolonged DAPT, expert consensus suggests that DAPT duration should be individualized based on ischemic versus bleeding risks. At this regard, the DAPT score has been recently proposed as standardized tool to identify patients who derive benefit or lack from a prolonged course of DAPT. However, a prospective assessment of the DAPT score is lacking and whether a personalized duration of DAPT based on the DAPT score improves the net clinical benefit remains unknown.
The objective of the study is to compared the safety and the efficacy of the Cre8 AES with the Synergy EES and a personalized DAPT duration based on the DAPT score with a standard DAPT duration among patients undergoing PCI.
Detailed description
The objective of the trial is:
- to evaluate the efficacy and safety of the Cre8 AES vs. the Synergy EES in a broadly unselected patient population with coronary artery disease undergoing PCI; ii) to compare the safety and efficacy of a personalized DAPT duration (3-, 6-, or 24-month) guided by the application of the DAPT score with a standard DAPT duration (12-month) after PCI.
In particular, the objectives of the trial are to test the following hypothesis:
- The Cre8 AES is non-inferior to the Synergy EES with regards to a device-oriented composite endpoint (DOCE) at 1-year follow-up.
- A personalized DAPT duration based on the DAPT score is superior to a standard DAPT duration with regards to a net adverse clinical endpoint (NACE) at 2-year follow-up.
This is a prospective, randomized, multicenter, investigator-initiated, assessor-blind trial to be conducted at interventional cardiology centers in Italy. Patients undergoing PCI will be randomized in a 2-by-2 randomization fashion to undergo PCI with the Cre8 AES or Synergy EES and to receive a personalized or standard DAPT duration. All patients will be followed at 3-, 6-, 12- and 24-month after PCI for clinical endpoints.
Use of experimental and control DES:
Both the study stent (Cre8 AES) and the control stent (Synergy EES) will be used according to their indications for use. The randomly assigned stent is not expected to have an influence on the conduct of the procedure that will take place according to the routine practice. Eligible patients will undergo PCI as per local protocol, according to current guidelines of the European Society of Cardiology on myocardial revascularization. The technique of PCI (vascular access route, choice of the vascular sheath diameter, choice of the diagnostic and guiding catheters sizes and shapes, choice of the coronary guidewire) will be left to the discretion of the operator as per standard individual and local practice. The operator will choose the appropriate length and diameter of the stents to be implanted by visual estimate or quantitative coronary angiography as per local practice. The Cre8 AES and the Synergy EES systems are commercially available and all sizes may be used for the study.
DAPT duration according to randomization:
DAPT duration in patients randomized to personalized DAPT regimen: In patients that are randomized to a personalized DAPT and have a low DAPT score (<2), DAPT duration is recommended for 3 months in case of stable coronary artery disease at the time of the index procedure or for 6 months in case of acute coronary syndrome at the time of the index procedure. A low dose of aspirin (75 to 162 mg daily) will be administered throughout the course of the study. In patients that are randomized to a personalized DAPT and have a high DAPT score (≥2), DAPT duration is recommended for 24 months. Changes in the dose or in the type of P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) are allowed during the course of the study. A low dose of aspirin (75 to 162 mg daily) will be administered throughout the course of the study. At 12-month, patients on treatment with prasugrel or ticagrelor should continue the same P2Y12 receptor inhibitor. In this specific scenario, it is preferable to continue with the same P2Y12 receptor inhibitor (prasugrel 10 mg daily or ticagrelor 90 mg daily) or to switch to a low-dose regimen of ticagrelor (60 mg twice daily) if clinically indicated or to switch to clopidogrel (75 mg daily).
DAPT regimen in patients in patients randomized to a standard DAPT duration: In patients that are randomized to a standard DAPT duration, oral P2Y12 inhibitors (clopidogrel, prasugrel, or ticagrelor) should be administered for 12-month. A low dose of aspirin (75 to 162 mg daily) will be administered throughout the course of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
- Model description
- 2-by-2 randomization
| Arm | Type | Receives |
|---|---|---|
| Cre8 AES and personalized DAPT duration | Other | Device: Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease., Drug: Personalized DAPT durationPercutaneous coronary intervention with implantation of a Cre8 amphilimus- eluting stent for coronary artery disease. Personalized duration of dual antiplatelet therapy for 3-, 6-, or 24-month after percutaneous coronary intervention based on the DAPT score. |
| Cre8 AES and standard DAPT duration | Other | Device: Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease., Drug: Standard DAPT durationPercutaneous coronary intervention with implantation of a Cre8 amphilimus- eluting stent for coronary artery disease. Standard duration of dual antiplatelet therapy for 12-month after percutaneous coronary intervention. |
| Synergy EES and personalized DAPT duration | Other | Device: Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease., Drug: Personalized DAPT durationPercutaneous coronary intervention with implantation of a Synergy everolimus-eluting stent for coronary artery disease. Personalized duration of dual antiplatelet therapy for 3-, 6-, or 24-month after percutaneous coronary intervention based on the DAPT score. |
| Synergy EES and standard DAPT duration | Other | Device: Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease., Drug: Standard DAPT durationPercutaneous coronary intervention with implantation of a Synergy everolimus-eluting stent for coronary artery disease. Standard duration of dual antiplatelet therapy for 12-month after percutaneous coronary intervention. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age ≥18 years;
- Clinical evidence of coronary artery disease requiring PCI with DES implantation;
- Any coronary lesion sized 2.25-4.5 mm by visual estimation.
Key exclusion criteria (10 listed)
- Inability to provide informed consent;
- Active bleeding requiring medical attention (BARC ≥2);
- Need for chronic oral anticoagulant therapy;
- Planned surgery within 3 months;
- Known hypersensitivity or allergy to aspirin or any P2Y12 receptor inhibitor (clopidogrel, prasugrel, ticagrelor), heparin, contrast agent, or any DES-components;
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 |
|---|---|---|
| Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease.Also: Cre8 AESImplantation of polymer-free, amphilimus-eluting, drug-eluting stents | Device | Cre8 AES and personalized DAPT duration, Cre8 AES and standard DAPT duration |
| Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease.Also: Synergy EESImplantation of biodegradable-polymer, everolimus-eluting, drug-eluting stents | Device | Synergy EES and personalized DAPT duration, Synergy EES and standard DAPT duration |
| Personalized DAPT durationDuration of dual antiplatelet therapy according to DAPT score for 3- or 6- months in patients with low DAPT score (stable CAD or ACS, respectively) or for 24-months in patients with high DAPT score | Drug | Cre8 AES and personalized DAPT duration, Synergy EES and personalized DAPT duration |
| Standard DAPT durationDuration of dual antiplatelet therapy for 12 months. | Drug | Cre8 AES and standard DAPT duration, Synergy EES and standard DAPT duration |
Primary outcome
Number of Participants with Device-oriented composite endpoint (DOCE) for the comparison between the Cre8 AES and the Synergy EES.
Time frame: 12 months
The composite of cardiovascular death, myocardial infarction not clearly attributable to a non-target vessel, or clinically-driven target-lesion revascularization.
Number of Participants with Net adverse clinical endpoint (NACE) for the comparison between a personalized and standard DAPT duration.
Time frame: 24 months
The composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or BARC type 2 to 5 bleeding at 24-month follow-up.
14 secondary outcomes
Number of Participants with All-cause death
Time frame: 12- and 24-month
Number of Participants with Death from cardiovascular causes
Time frame: 12- and 24-month
Number of Participants with Myocardial infarction
Time frame: 12- and 24-month
Number of Participants with Stroke
Time frame: 12- and 24-month
Number of Participants with Clinically-driven target-lesion revascularization
Time frame: 12- and 24-month
Number of Participants with Definite or probable stent thrombosis
Time frame: 12- and 24-month
Number of Participants with Definite stent thrombosis
Time frame: 12- and 24-month
Number of Participants with Any revascularization
Time frame: 12- and 24-month
Number of Participants with Clinically-driven target-vessel revascularization
Time frame: 12- and 24-month
Number of Participants with Urgent target-vessel revascularization
Time frame: 12- and 24-month
Number of Participants with Urgent non-target-vessel revascularization
Time frame: 12- and 24-month
Number of Participants with Any target-lesion revascularization
Time frame: 12- and 24-month
Number of Participants with Any target-vessel revascularization
Time frame: 12- and 24-month
Number of Participants with Bleeding events
Time frame: 12- and 24-month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2024.
- Background: PubMed 26858081Piccolo R, Windecker S. Dual Antiplatelet Therapy in Percutaneous Coronary Intervention: A Tale of 2 Decades With New Perspectives in the Era of New-Generation Drug-Eluting Stents. Circ Cardiovasc Interv. 2016 Feb;9(2):e003587. doi: 10.1161/CIRCINTERVENTIONS.116.003587. No abstract available.
- Background: PubMed 28886622Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Juni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN; ESC Scientific Document Group; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2018 Jan 14;39(3):213-260. doi: 10.1093/eurheartj/ehx419. No abstract available.
- Background: PubMed 26005909Spencer FA, Prasad M, Vandvik PO, Chetan D, Zhou Q, Guyatt G. Longer- Versus Shorter-Duration Dual-Antiplatelet Therapy After Drug-Eluting Stent Placement: A Systematic Review and Meta-analysis. Ann Intern Med. 2015 Jul 21;163(2):118-26. doi: 10.7326/M15-0083.
- Background: PubMed 27036919Bittl JA, Baber U, Bradley SM, Wijeysundera DN. Duration of Dual Antiplatelet Therapy: A Systematic Review for the 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Sep 6;68(10):1116-39. doi: 10.1016/j.jacc.2016.03.512. Epub 2016 Mar 29.
- Background: PubMed 27036918Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC Jr. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016 Sep 6;68(10):1082-115. doi: 10.1016/j.jacc.2016.03.513. Epub 2016 Mar 29. No abstract available.
- Background: PubMed 27462674Raber L, Piccolo R. CardioPulse: Different bleeding scores and which one should we use? Eur Heart J. 2016 Jan 21;37(4):327-31. No abstract available.
- Background: PubMed 27022822Yeh RW, Secemsky EA, Kereiakes DJ, Normand SL, Gershlick AH, Cohen DJ, Spertus JA, Steg PG, Cutlip DE, Rinaldi MJ, Camenzind E, Wijns W, Apruzzese PK, Song Y, Massaro JM, Mauri L; DAPT Study Investigators. Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention. JAMA. 2016 Apr 26;315(16):1735-49. doi: 10.1001/jama.2016.3775.
- Background: PubMed 28605779Piccolo R, Gargiulo G, Franzone A, Santucci A, Ariotti S, Baldo A, Tumscitz C, Moschovitis A, Windecker S, Valgimigli M. Use of the Dual-Antiplatelet Therapy Score to Guide Treatment Duration After Percutaneous Coronary Intervention. Ann Intern Med. 2017 Jul 4;167(1):17-25. doi: 10.7326/M16-2389. Epub 2017 Jun 13.
- Background: PubMed 30586704Rozemeijer R, Stein M, Voskuil M, van den Bor R, Frambach P, Pereira B, Koudstaal S, Leenders GE, Timmers L, Rittersma SZ, Kraaijeveld AO, Agostoni P, Roes KC, Doevendans PA, Stella PR; ReCre8 Study Investigators. Randomized All-Comers Evaluation of a Permanent Polymer Zotarolimus-Eluting Stent Versus a Polymer-Free Amphilimus-Eluting Stent. Circulation. 2019 Jan 2;139(1):67-77. doi: 10.1161/CIRCULATIONAHA.118.037707.
- Background: PubMed 25883067Navarese EP, Andreotti F, Schulze V, Kolodziejczak M, Buffon A, Brouwer M, Costa F, Kowalewski M, Parati G, Lip GY, Kelm M, Valgimigli M. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials. BMJ. 2015 Apr 16;350:h1618. doi: 10.1136/bmj.h1618.
- Background: PubMed 29891620Garcia-Garcia HM, McFadden EP, Farb A, Mehran R, Stone GW, Spertus J, Onuma Y, Morel MA, van Es GA, Zuckerman B, Fearon WF, Taggart D, Kappetein AP, Krucoff MW, Vranckx P, Windecker S, Cutlip D, Serruys PW; Academic Research Consortium. Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document. Circulation. 2018 Jun 12;137(24):2635-2650. doi: 10.1161/CIRCULATIONAHA.117.029289.
- Derived from this study: PubMed 40892607Piccolo R, Calabro P, Carrara G, Simonetti F, Varricchio A, Attisano T, Napolitano G, De Simone C, Carpinella G, Stabile E, Cirillo P, Di Serafino L, Caiazzo G, Tesorio T, Boccalatte M, Tuccillo B, Avvedimento M, Leone A, Galasso G, Cesaro A, Perrotta R, Niglio T, Castiello DS, Immobile Molaro M, Bardi L, Spinelli A, Cristiano S, Bellino M, Leonardi S, Biscaglia S, Costa F, Cassese S, McFadden E, Heg D, Stefanini GG, Franzone A, Capodanno D, Esposito G; PARTHENOPE Study Group. Personalized or Standard Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: The PARTHENOPE Randomized Trial. J Am Coll Cardiol. 2025 Dec 9;86(23):2352-2367. doi: 10.1016/j.jacc.2025.08.040. Epub 2025 Aug 30.
- 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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease., Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease. and Personalized DAPT duration in people with Coronary Artery Disease and Acute Coronary Syndrome, run by Federico II University at 13 sites in Italy.
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 3 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Italy. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Device-oriented composite endpoint (DOCE) for the comparison between the Cre8 AES and the Synergy EES. (time frame: 12 months). The study lists 2 primary outcomes in all. 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 NCT04135989, which also lists 14 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 23 Feb 2024.