De-escalating Antiplatelet Therapy to Assess Platelet Reactivity and Outcomes in High Bleeding Risk Patients With Recent ACS

NCT ID: NCT05903976

Last Updated: 2023-08-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-12
• Study Completion Date: 2025-10-30

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.

Conditions

Dual Antiplatelet Therapy; Acute Coronary Syndrome; Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CLOPIDOGREL 75 mg qd

50 patients treated with clopidogrel 75mg

Group Type: EXPERIMENTAL

P2Y12 inhibitor de-escalation

Intervention Type: DRUG

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.

PRASUGREL 5mg qd

50 patients treated with prasugrel 5mg

Group Type: EXPERIMENTAL

P2Y12 inhibitor de-escalation

Intervention Type: DRUG

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.

TICAGRELOR 60mg bid

50 patients treated with ticagrelor 60mg bid

Group Type: EXPERIMENTAL

P2Y12 inhibitor de-escalation

Intervention Type: DRUG

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.

Continue Potent P2Y12i Full-Dose

50 patients in the full-dose potent P2Y12 inhibitor (prasugrel 10 mg or ticagrelor 90 mg bid according to prior prescription)

Group Type: ACTIVE_COMPARATOR

P2Y12 inhibitor de-escalation

Intervention Type: DRUG

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.

Interventions

P2Y12 inhibitor de-escalation

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Giampiero Vizzari

UNKNOWN

Sponsor Role: collaborator

Giorgio Quadri

UNKNOWN

Sponsor Role: collaborator

Greca Zanda

UNKNOWN

Sponsor Role: collaborator

Ferdinando Varbella

UNKNOWN

Sponsor Role: collaborator

Gianluca Di Bella

UNKNOWN

Sponsor Role: collaborator

Antonio Micari

UNKNOWN

Sponsor Role: collaborator

Azienda Ospedaliera Universitaria Policlinico "G. Martino"

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Azienda Ospedaliera Universitaria Gaetano Martino

Messina, , Italy

Site Status: RECRUITING

Ospedale degli Infermi

Rivoli, , Italy

Site Status: NOT_YET_RECRUITING

Countries

Italy

Central Contacts

Francesco Costa, MD, PhD

Role: CONTACT

francesco.costa@unime.it

+39090221 ext. 2341

Facility Contacts

Francesco Costa, MD, PhD

Role: primary

Greca Zanda, MD

Role: primary

Other Identifiers

DESC-HBR

Identifier Type: -

Identifier Source: org_study_id