Personalized Vs. Standard Duration of Dual Antiplatelet Therapy and New-generation Polymer-Free vs- Biodegradable-Polymer DES

NCT04135989 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: 197/19
• Study Type: interventional
• Target: 2,106
• Locations: 1 country
• Sites: 13

Brief 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 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.

Conditions

Coronary Artery Disease; Acute Coronary Syndrome; Chronic Coronary Syndrome; Myocardial Infarction

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  24 months

Secondary Outcomes (14)

• Number of Participants with All-cause death

  12- and 24-month

• Number of Participants with Death from cardiovascular causes

  12- and 24-month

• Number of Participants with Myocardial infarction

  12- and 24-month

• Number of Participants with Stroke

  12- and 24-month

• Number of Participants with Clinically-driven target-lesion revascularization

  12- and 24-month

Study Arms (4)

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.

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.

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.

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.

Device: Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease.; Drug: Standard DAPT duration

Interventions

Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease. DEVICE

Implantation of polymer-free, amphilimus-eluting, drug-eluting stents

Also known as: Cre8 AES

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. DEVICE

Implantation of biodegradable-polymer, everolimus-eluting, drug-eluting stents

Also known as: Synergy EES

Synergy EES and personalized DAPT duration; Synergy EES and standard DAPT duration

Personalized DAPT duration DRUG

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

Cre8 AES and personalized DAPT duration; Synergy EES and personalized DAPT duration

Standard DAPT duration DRUG

Duration of dual antiplatelet therapy for 12 months.

Cre8 AES and standard DAPT duration; Synergy EES and standard DAPT duration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Federico II University: lead
• AdvicePharma Group: collaborator

Study Sites (13)

Casa di Cura Villa Dei Fiori

Acerra, Naples, 80011, Italy

Location

Ospedale S.Maria delle Grazie

Pozzuoli, Naples, 80078, Italy

Location

Ospedale "Maria SS. Addolorata"

Eboli, SA, 84025, Italy

Location

A.O.R.N. S.Giuseppe Moscati-Città Ospedaliera

Avellino, 83100, Italy

Location

Ospedale San Giuseppe Moscati

Aversa, 81031, Italy

Location

A.O.R.N. Sant'Anna e San Sebastiano

Caserta, 81100, Italy

Location

Ospedale San Giuliano

Giugliano in Campania, 80014, Italy

Location

Federico II University of Naples

Naples, 80131, Italy

Location

A.O.R.N. A. Cardarelli

Napoli, 80131, Italy

Location

Ospedale San Giovanni Bosco - ASL Napoli 1

Napoli, 80131, Italy

Location

Ospedale del Mare

Napoli, 80147, Italy

Location

Ospedale Santa Maria della Pietà

Nola, 80035, Italy

Location

AOU San Giovanni di Dio e Ruggi d'Aragona

Salerno, 84131, Italy

Location

Related Publications (14)

• 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.

  PMID: 26858081 BACKGROUND

• Valgimigli 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.

  PMID: 28886622 BACKGROUND

• Spencer 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.

  PMID: 26005909 BACKGROUND

• Bittl 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.

  PMID: 27036919 BACKGROUND

• Levine 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.

  PMID: 27036918 BACKGROUND

• Raber 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.

  PMID: 27462674 BACKGROUND

• Yeh 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.

  PMID: 27022822 BACKGROUND

• Piccolo 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.

  PMID: 28605779 BACKGROUND

• Rozemeijer 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.

  PMID: 30586704 BACKGROUND

• Navarese 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.

  PMID: 25883067 BACKGROUND

• Garcia-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.

  PMID: 29891620 BACKGROUND

• Piccolo 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.

  PMID: 40892607 DERIVED

• Piccolo 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.

  PMID: 39773824 DERIVED

• Piccolo 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.

  PMID: 37572785 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Acute Coronary Syndrome; Myocardial Infarction

Interventions

Percutaneous Coronary Intervention

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Endovascular Procedures; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology

Model Details: 2-by-2 randomization

Study Record Dates

• First Submitted: October 21, 2019
• First Posted: October 23, 2019
• Study Start: January 1, 2020
• Primary Completion: October 24, 2021
• Study Completion: October 24, 2024
• Last Updated: February 23, 2024

Record last verified: 2024-02

Locations

IT (13)