Back to resultsDe-escalating Antiplatelet Therapy to Assess Platelet Reactivity and Outcomes in High Bleeding Risk Patients With Recent ACS (DESC-HBR)
Primary Purpose
Dual Antiplatelet Therapy, Acute Coronary Syndrome, Coronary Artery Disease
Status
Recruiting
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
P2Y12 inhibitor de-escalation
Sponsored by
About this trial
This is an interventional treatment trial for Dual Antiplatelet Therapy focused on measuring DAPT De-escalation, P2Y12 inhibitors
Eligibility Criteria
Participants fulfilling all the following inclusion criteria are eligible for the study: Informed Consent signed and dated. Patients deemed at HBR according to standard definitions (i.e. PRECISE-DAPT ≥25 or HBR-ARC with at least 1 major or 2 minor criteria). Treated with PCI due to a recent ACS (i.e. unstable angina, non-ST segment elevated myocardial infarction or ST segment elevated myocardial infarction) 30 ±7 days earlier. Treated with DAPT with full-dose potent P2Y12 inhibitors (e.g. prasugrel 10mg or ticagrelor 90mg bid) according to international guidelines recommendations. The presence of anyone of the following exclusion criteria will lead to exclusion of the participant: Age < 18 years Known intolerance, hypersensitivity or contraindication (including active bleeding) to aspirin, clopidogrel, prasugrel, ticagrelor or to any of the excipients Indication to oral anticoagulation Indication to prolonged treatment with full-dose potent P2Y12 inhibitors (e.g. previous stent thrombosis, stenting of last remaining vessel, stent with indication for longer-term DAPT, perceived very high coronary ischemic risk) Any planned major surgery or interventional procedure requiring treatment modification Prior transient ischemic attack, ischemic or haemorrhagic stroke Severe hepatic insufficiency (Child-Pugh class C) Ongoing therapy with strong CYP3A inducers or strong CYP3A inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir, atazanavir etc.) Women who are pregnant, breast feeding or of childbearing potential (i.e. fertile, following menarche and who are not surgically sterile, including hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or post-menopausal defined as no menses for 12 months without an alternative medical cause); Participation in another study with investigational drug within the 30 days, or 5 half-lives of the study drug whichever is longer, preceding and during the present study Enrolment of the investigator, his/her family members, employees Inability to follow the procedures of the study (language problems, mental disorders, dementia) or comorbidities associated with less than 12 months-life expectation (active malignancies drug or alcohol abuse, etc.) or other conditions that might result in protocol non-compliance.
Sites / Locations
- Azienda Ospedaliera Universitaria Gaetano MartinoRecruiting
- Ospedale degli Infermi
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
CLOPIDOGREL 75 mg qd
PRASUGREL 5mg qd
TICAGRELOR 60mg bid
Continue Potent P2Y12i Full-Dose
Arm Description
50 patients treated with clopidogrel 75mg
50 patients treated with prasugrel 5mg
50 patients treated with ticagrelor 60mg bid
50 patients in the full-dose potent P2Y12 inhibitor (prasugrel 10 mg or ticagrelor 90 mg bid according to prior prescription)
Outcomes
Primary Outcome Measures
Proportion of Patients Achieving Optimal Platelet Reactivity (OPR) at peak level following Drug Maintenance Dose (MD) Using the VerifyNow System
The incidence of optimal platelet reactivity (OPR) measured by means of the VerifyNow system. OPR will be defined as a PRU between 85 and 208 reactivity units according to international expert consensus.
Secondary Outcome Measures
Incidence of Bleeding Events According to Multiple Bleeding Definitions
The incidence of nuisance, minor or major bleeding according to the BARC definition (BARC 1-5).
Platelet reactive units (PRU) at VerifyNow system
Platelet reactive units (PRU) measurement at VerifyNow system
Proportion of high platelet reactivity (HPR) and the proportion of low platelet reactivity (LPR) measured through the VerifyNow system
The proportion of high platelet reactivity (HPR) defined as PRU > 208, and the proportion of low platelet reactivity (LPR), defined as PRU < 85, measured through the VerifyNow system before first randomized treatment administration (baseline), 2 hours after the first randomized treatment administration, before MD at 14±2 days from study inclusion and at 2 hours after drug MD administration at 14±2 days from study inclusion. PRU at 1 and 2 weeks after P2Y12 inhibitor discontinuation study in patients permanently ceasing treatment.
Platelet-derived thrombogenicity at Total Thrombus Formation (T-TAS)
Platelet-derived thrombogenicity at Total Thrombus Formation (T-TAS) before first randomized treatment administration (baseline), 2 hours after the first randomized treatment administration, before and after MD at 14±2 days from study inclusion.
Adverse clinical event
Adverse clinical events, assessed at each visit and up to 5 months after randomization. They include: death, cardiac death, non-fatal myocardial infarction, non-fatal stroke, urgent target vessel revascularization, definite/probable stent thrombosis and net adverse clinical events.
Cost-effectiveness
Cost-effectives analysis will be carried out by inputting direct and indirect costs in relation to outcomes assessed.
Full Information
NCT ID
NCT05903976
First Posted
May 26, 2023
Last Updated
August 22, 2023
Sponsor
Azienda Ospedaliera Universitaria Policlinico "G. Martino"
Collaborators
Giampiero Vizzari, Giorgio Quadri, Greca Zanda, Ferdinando Varbella, Gianluca Di Bella, Antonio Micari
1. Study Identification
Unique Protocol Identification Number
NCT05903976
Brief Title
De-escalating Antiplatelet Therapy to Assess Platelet Reactivity and Outcomes in High Bleeding Risk Patients With Recent ACS
Acronym
DESC-HBR
Official Title
De-Escalation of Antiplatelet Therapy to Evaluate Platelet Reactivity and Clinical Outcomes After Coronary Stenting in Patients at High Bleeding Risk and Recent Acute Coronary Syndrome: DESC-HBR Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 12, 2023 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
October 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Azienda Ospedaliera Universitaria Policlinico "G. Martino"
Collaborators
Giampiero Vizzari, Giorgio Quadri, Greca Zanda, Ferdinando Varbella, Gianluca Di Bella, Antonio Micari
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
5. Study Description
Brief Summary
High bleeding risk (HBR) patients, comprising up to 50% of those presenting with acute coronary syndrome (ACS), are a high-risk group that is increasing in size due to an aging population. The optimal selection of the potency and duration of antiplatelet therapy to reduce the risk of recurrent ischemic and bleeding events in HBR patients is still a matter of debate. Multiple strategies to reduce bleeding during secondary prevention, such as reducing the duration of dual antiplatelet therapy, using single antiplatelet therapy with a P2Y12 inhibitor, or de-escalating to a lower potency or lower-dose P2Y12 inhibitor, have been proposed. De-escalation to a lower potency or lower-dose P2Y12 inhibitor is particularly attractive because it maintains efficient pharmacological inhibition of multiple platelet pathways while potentially reducing bleeding through less aggressive activity. Yet, there has been no study comparing the effects of different de-escalation strategies with the standard potent P2Y12 inhibitors in HBR patients. The aim of the DESC-HBR study is to assess the impact of de-escalating P2Y12 inhibitor to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg bid in HBR patients, in comparison with full-dose potent P2Y12 inhibitors, on the proportion of patients with optimal platelet reactivity (OPR). Secondary objectives involve exploring the effect of de-escalation on clinical events and patients' quality of life.
Detailed Description
The aim of the DESC-HBR trial is to compare the impact of de-escalating P2Y12 inhibitor to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg bid, with full-dose potent P2Y12 inhibitors, on the proportion of patients with optimal platelet reactivity (OPR). The secondary objective is to explore the effect of de-escalating P2Y12 inhibitor therapy on clinical events and patients' quality of life. The primary outcome is the proportion of patients in the OPR range measured through the VerifyNow system at peak level after drug maintenance dose (MD) at 14±2 days. OPR is defined as a platelet reactive unit (PRU) between 85 and 208 reactivity units based on international consensus. A key secondary outcome will be major, minor and nuisance bleeding according to the bleeding academic research consortium (BARC) definition up to 5 months. Secondary pharmacodynamic outcomes include platelet reactivity with the VerifyNow and T-TAS system at different timepoints (baseline, 2h after first dose, through levels before MD and peak levels after MD at 14±2 days). Further pharmacodynamic assessment at 1 and 2 weeks after P2Y12 inhibitor discontinuation will be performed in the subset of patients discontinuing P2Y12 inhibitor at study conclusion or in case of P2Y12 discontinuation at anytime during the study.Other secondary endpoints will be explored including all-cause death, major adverse cardiac and cerebrovascular events (MACCE), a composite of cardiac death, myocardial infarction (MI), target vessel revascularization (TVR) and stroke, net adverse clinical events (NACE), a composite of MACCE and BARC 2-5 bleeding, and each individual endpoint singularly appraised. Quality of life will be evaluated with health mobility and performance scales (i.e. EQ-5D-5L, SF-12), perceived stress scale (i.e. PPS).Cost-effectives analysis will be also carried out by inputting direct and indirect costs in relation to outcomes. Study visits are scheduled at baseline,14±2 days, 3 and 5 months after randomization.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dual Antiplatelet Therapy, Acute Coronary Syndrome, Coronary Artery Disease
Keywords
DAPT De-escalation, P2Y12 inhibitors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CLOPIDOGREL 75 mg qd
Arm Type
Experimental
Arm Description
50 patients treated with clopidogrel 75mg
Arm Title
PRASUGREL 5mg qd
Arm Type
Experimental
Arm Description
50 patients treated with prasugrel 5mg
Arm Title
TICAGRELOR 60mg bid
Arm Type
Experimental
Arm Description
50 patients treated with ticagrelor 60mg bid
Arm Title
Continue Potent P2Y12i Full-Dose
Arm Type
Active Comparator
Arm Description
50 patients in the full-dose potent P2Y12 inhibitor (prasugrel 10 mg or ticagrelor 90 mg bid according to prior prescription)
Intervention Type
Drug
Intervention Name(s)
P2Y12 inhibitor de-escalation
Intervention Description
Comparing, in patients at High Bleeding Risk (HBR) after a recent Acute Coronary Syndrome (ACS), continuation of full-dose potent P2Y12 inhibitor with a P2Y12i de-escalation strategy transitioning to clopidogrel 75mg, prasugrel 5mg or ticagrelor 60mg/bid.
Primary Outcome Measure Information:
Title
Proportion of Patients Achieving Optimal Platelet Reactivity (OPR) at peak level following Drug Maintenance Dose (MD) Using the VerifyNow System
Description
The incidence of optimal platelet reactivity (OPR) measured by means of the VerifyNow system. OPR will be defined as a PRU between 85 and 208 reactivity units according to international expert consensus.
Time Frame
2 hours after drug MD at 14±2 days from study inclusion
Secondary Outcome Measure Information:
Title
Incidence of Bleeding Events According to Multiple Bleeding Definitions
Description
The incidence of nuisance, minor or major bleeding according to the BARC definition (BARC 1-5).
Time Frame
5 Months after enrollment
Title
Platelet reactive units (PRU) at VerifyNow system
Description
Platelet reactive units (PRU) measurement at VerifyNow system
Time Frame
baseline, 2 hours after the first treatment administration and before MD at 14±2 days from study inclusion
Title
Proportion of high platelet reactivity (HPR) and the proportion of low platelet reactivity (LPR) measured through the VerifyNow system
Description
The proportion of high platelet reactivity (HPR) defined as PRU > 208, and the proportion of low platelet reactivity (LPR), defined as PRU < 85, measured through the VerifyNow system before first randomized treatment administration (baseline), 2 hours after the first randomized treatment administration, before MD at 14±2 days from study inclusion and at 2 hours after drug MD administration at 14±2 days from study inclusion. PRU at 1 and 2 weeks after P2Y12 inhibitor discontinuation study in patients permanently ceasing treatment.
Time Frame
baseline, 2 hours after the first treatment administration, before MD at 14±2 days from study inclusion and at 2 hours after drug MD administration at 14±2 days
Title
Platelet-derived thrombogenicity at Total Thrombus Formation (T-TAS)
Description
Platelet-derived thrombogenicity at Total Thrombus Formation (T-TAS) before first randomized treatment administration (baseline), 2 hours after the first randomized treatment administration, before and after MD at 14±2 days from study inclusion.
Time Frame
baseline, 2 hours after the first treatment administration, before and after MD at 14±2 days from study inclusion.
Title
Adverse clinical event
Description
Adverse clinical events, assessed at each visit and up to 5 months after randomization. They include: death, cardiac death, non-fatal myocardial infarction, non-fatal stroke, urgent target vessel revascularization, definite/probable stent thrombosis and net adverse clinical events.
Time Frame
14±2 days, 3 and 5 months from study inclusion
Title
Cost-effectiveness
Description
Cost-effectives analysis will be carried out by inputting direct and indirect costs in relation to outcomes assessed.
Time Frame
5 Months after enrollment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Participants fulfilling all the following inclusion criteria are eligible for the study:
Informed Consent signed and dated.
Patients deemed at HBR according to standard definitions (i.e. PRECISE-DAPT ≥25 or HBR-ARC with at least 1 major or 2 minor criteria).
Treated with PCI due to a recent ACS (i.e. unstable angina, non-ST segment elevated myocardial infarction or ST segment elevated myocardial infarction) 30 ±7 days earlier.
Treated with DAPT with full-dose potent P2Y12 inhibitors (e.g. prasugrel 10mg or ticagrelor 90mg bid) according to international guidelines recommendations.
The presence of anyone of the following exclusion criteria will lead to exclusion of the participant:
Age < 18 years
Known intolerance, hypersensitivity or contraindication (including active bleeding) to aspirin, clopidogrel, prasugrel, ticagrelor or to any of the excipients
Indication to oral anticoagulation
Indication to prolonged treatment with full-dose potent P2Y12 inhibitors (e.g. previous stent thrombosis, stenting of last remaining vessel, stent with indication for longer-term DAPT, perceived very high coronary ischemic risk)
Any planned major surgery or interventional procedure requiring treatment modification
Prior transient ischemic attack, ischemic or haemorrhagic stroke
Severe hepatic insufficiency (Child-Pugh class C)
Ongoing therapy with strong CYP3A inducers or strong CYP3A inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir, atazanavir etc.)
Women who are pregnant, breast feeding or of childbearing potential (i.e. fertile, following menarche and who are not surgically sterile, including hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or post-menopausal defined as no menses for 12 months without an alternative medical cause); Participation in another study with investigational drug within the 30 days, or 5 half-lives of the study drug whichever is longer, preceding and during the present study
Enrolment of the investigator, his/her family members, employees
Inability to follow the procedures of the study (language problems, mental disorders, dementia) or comorbidities associated with less than 12 months-life expectation (active malignancies drug or alcohol abuse, etc.) or other conditions that might result in protocol non-compliance.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Francesco Costa, MD, PhD
Phone
+39090221
Ext
2341
Email
francesco.costa@unime.it
Facility Information:
Facility Name
Azienda Ospedaliera Universitaria Gaetano Martino
City
Messina
ZIP/Postal Code
98125
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francesco Costa, MD, PhD
First Name & Middle Initial & Last Name & Degree
Francesco Costa, MD, PhD
Facility Name
Ospedale degli Infermi
City
Rivoli
ZIP/Postal Code
10098
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Greca Zanda, MD
First Name & Middle Initial & Last Name & Degree
Giorgio Quadri, MD
First Name & Middle Initial & Last Name & Degree
Greca Zanda, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
De-escalating Antiplatelet Therapy to Assess Platelet Reactivity and Outcomes in High Bleeding Risk Patients With Recent ACS
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