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

Primary Purpose

Coronary Artery Disease, Acute Coronary Syndrome, Chronic Coronary Syndrome

Status
Active
Phase
Phase 4
Locations
Italy
Study Type
Interventional
Intervention
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
Sponsored by
Federico II University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥18 years;
  2. Clinical evidence of coronary artery disease requiring PCI with DES implantation;
  3. Any coronary lesion sized 2.25-4.5 mm by visual estimation.

Exclusion Criteria:

  1. Inability to provide informed consent;
  2. Active bleeding requiring medical attention (BARC ≥2);
  3. Need for chronic oral anticoagulant therapy;
  4. Planned surgery within 3 months;
  5. Known hypersensitivity or allergy to aspirin or any P2Y12 receptor inhibitor (clopidogrel, prasugrel, ticagrelor), heparin, contrast agent, or any DES-components;
  6. Previous treatment with bioresorbable vascular scaffolds;
  7. Participation in another study that has not reached the primary endpoint;
  8. A life expectancy of less than 24 months;
  9. Female of childbearing potential;
  10. Under judicial protection, tutorship or curatorship.

Sites / Locations

  • Casa di Cura Villa Dei Fiori
  • Ospedale S.Maria delle Grazie
  • Ospedale "Maria SS. Addolorata"
  • A.O.R.N. S.Giuseppe Moscati-Città Ospedaliera
  • Ospedale San Giuseppe Moscati
  • A.O.R.N. Sant'Anna e San Sebastiano
  • Ospedale San Giuliano
  • Federico II University of Naples
  • A.O.R.N. A. Cardarelli
  • Ospedale San Giovanni Bosco - ASL Napoli 1
  • Ospedale del Mare
  • Ospedale Santa Maria della Pietà
  • AOU San Giovanni di Dio e Ruggi d'Aragona

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Other

Other

Other

Arm Label

Cre8 AES and personalized DAPT duration

Cre8 AES and standard DAPT duration

Synergy EES and personalized DAPT duration

Synergy EES and standard DAPT duration

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Number of Participants with All-cause death
Number of Participants with Death from cardiovascular causes
Number of Participants with Myocardial infarction
Number of Participants with Stroke
Number of Participants with Clinically-driven target-lesion revascularization
Number of Participants with Definite or probable stent thrombosis
Number of Participants with Definite stent thrombosis
Number of Participants with Any revascularization
Number of Participants with Clinically-driven target-vessel revascularization
Number of Participants with Urgent target-vessel revascularization
Number of Participants with Urgent non-target-vessel revascularization
Number of Participants with Any target-lesion revascularization
Number of Participants with Any target-vessel revascularization
Number of Participants with Bleeding events
Bleeding events according to the BARC, TIMI and GUSTO classification

Full Information

First Posted
October 21, 2019
Last Updated
July 8, 2022
Sponsor
Federico II University
Collaborators
AdvicePharma Group
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1. Study Identification

Unique Protocol Identification Number
NCT04135989
Brief Title
Personalized Vs. Standard Duration of Dual Antiplatelet Therapy and New-generation Polymer-Free vs- Biodegradable-Polymer DES
Acronym
PARTHENOPE
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 1, 2020 (Actual)
Primary Completion Date
October 24, 2021 (Actual)
Study Completion Date
October 24, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Federico II University
Collaborators
AdvicePharma Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
The objective of the trial is: i) 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease, Acute Coronary Syndrome, Chronic Coronary Syndrome, Myocardial Infarction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Factorial Assignment
Model Description
2-by-2 randomization
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
2106 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cre8 AES and personalized DAPT duration
Arm Type
Other
Arm Description
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.
Arm Title
Cre8 AES and standard DAPT duration
Arm Type
Other
Arm Description
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.
Arm Title
Synergy EES and personalized DAPT duration
Arm Type
Other
Arm Description
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.
Arm Title
Synergy EES and standard DAPT duration
Arm Type
Other
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Percutaneous coronary intervention with implantation of amphilimus-eluting stents for coronary artery disease.
Other Intervention Name(s)
Cre8 AES
Intervention Description
Implantation of polymer-free, amphilimus-eluting, drug-eluting stents
Intervention Type
Device
Intervention Name(s)
Percutaneous coronary intervention with implantation of everolimus-eluting stents for coronary artery disease.
Other Intervention Name(s)
Synergy EES
Intervention Description
Implantation of biodegradable-polymer, everolimus-eluting, drug-eluting stents
Intervention Type
Drug
Intervention Name(s)
Personalized DAPT duration
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Standard DAPT duration
Intervention Description
Duration of dual antiplatelet therapy for 12 months.
Primary Outcome Measure Information:
Title
Number of Participants with Device-oriented composite endpoint (DOCE) for the comparison between the Cre8 AES and the Synergy EES.
Description
The composite of cardiovascular death, myocardial infarction not clearly attributable to a non-target vessel, or clinically-driven target-lesion revascularization.
Time Frame
12 months
Title
Number of Participants with Net adverse clinical endpoint (NACE) for the comparison between a personalized and standard DAPT duration.
Description
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.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Number of Participants with All-cause death
Time Frame
12- and 24-month
Title
Number of Participants with Death from cardiovascular causes
Time Frame
12- and 24-month
Title
Number of Participants with Myocardial infarction
Time Frame
12- and 24-month
Title
Number of Participants with Stroke
Time Frame
12- and 24-month
Title
Number of Participants with Clinically-driven target-lesion revascularization
Time Frame
12- and 24-month
Title
Number of Participants with Definite or probable stent thrombosis
Time Frame
12- and 24-month
Title
Number of Participants with Definite stent thrombosis
Time Frame
12- and 24-month
Title
Number of Participants with Any revascularization
Time Frame
12- and 24-month
Title
Number of Participants with Clinically-driven target-vessel revascularization
Time Frame
12- and 24-month
Title
Number of Participants with Urgent target-vessel revascularization
Time Frame
12- and 24-month
Title
Number of Participants with Urgent non-target-vessel revascularization
Time Frame
12- and 24-month
Title
Number of Participants with Any target-lesion revascularization
Time Frame
12- and 24-month
Title
Number of Participants with Any target-vessel revascularization
Time Frame
12- and 24-month
Title
Number of Participants with Bleeding events
Description
Bleeding events according to the BARC, TIMI and GUSTO classification
Time Frame
12- and 24-month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Facility Information:
Facility Name
Casa di Cura Villa Dei Fiori
City
Acerra
State/Province
Naples
ZIP/Postal Code
80011
Country
Italy
Facility Name
Ospedale S.Maria delle Grazie
City
Pozzuoli
State/Province
Naples
ZIP/Postal Code
80078
Country
Italy
Facility Name
Ospedale "Maria SS. Addolorata"
City
Eboli
State/Province
SA
ZIP/Postal Code
84025
Country
Italy
Facility Name
A.O.R.N. S.Giuseppe Moscati-Città Ospedaliera
City
Avellino
ZIP/Postal Code
83100
Country
Italy
Facility Name
Ospedale San Giuseppe Moscati
City
Aversa
ZIP/Postal Code
81031
Country
Italy
Facility Name
A.O.R.N. Sant'Anna e San Sebastiano
City
Caserta
ZIP/Postal Code
81100
Country
Italy
Facility Name
Ospedale San Giuliano
City
Giugliano In Campania
ZIP/Postal Code
80014
Country
Italy
Facility Name
Federico II University of Naples
City
Naples
ZIP/Postal Code
80131
Country
Italy
Facility Name
A.O.R.N. A. Cardarelli
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Ospedale San Giovanni Bosco - ASL Napoli 1
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Ospedale del Mare
City
Napoli
ZIP/Postal Code
80147
Country
Italy
Facility Name
Ospedale Santa Maria della Pietà
City
Nola
ZIP/Postal Code
80035
Country
Italy
Facility Name
AOU San Giovanni di Dio e Ruggi d'Aragona
City
Salerno
ZIP/Postal Code
84131
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
26858081
Citation
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Citation
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Citation
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.
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Citation
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.
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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. Erratum In: JAMA. 2016 Jul 19;316(3):350. JAMA. 2016 Jul 19;316(3):350.
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Personalized Vs. Standard Duration of Dual Antiplatelet Therapy and New-generation Polymer-Free vs- Biodegradable-Polymer DES

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