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

NCT05903976 | Unknown Phase 3

• 1 other identifier: DESC-HBR
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

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.

Conditions

Dual Antiplatelet Therapy; Acute Coronary Syndrome; Coronary Artery Disease

Keywords

DAPT De-escalation; P2Y12 inhibitors

Outcome Measures

Primary Outcomes (1)

• 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.

  2 hours after drug MD at 14±2 days from study inclusion

Secondary Outcomes (6)

• Incidence of Bleeding Events According to Multiple Bleeding Definitions

  5 Months after enrollment

• Platelet reactive units (PRU) at VerifyNow system

  baseline, 2 hours after the first treatment administration and before MD at 14±2 days from study inclusion

• Proportion of high platelet reactivity (HPR) and the proportion of low platelet reactivity (LPR) measured through the VerifyNow system

  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

• Platelet-derived thrombogenicity at Total Thrombus Formation (T-TAS)

  baseline, 2 hours after the first treatment administration, before and after MD at 14±2 days from study inclusion.

• Adverse clinical event

  14±2 days, 3 and 5 months from study inclusion

Study Arms (4)

CLOPIDOGREL 75 mg qd

EXPERIMENTAL

50 patients treated with clopidogrel 75mg

Drug: P2Y12 inhibitor de-escalation

PRASUGREL 5mg qd

EXPERIMENTAL

50 patients treated with prasugrel 5mg

Drug: P2Y12 inhibitor de-escalation

TICAGRELOR 60mg bid

EXPERIMENTAL

50 patients treated with ticagrelor 60mg bid

Drug: P2Y12 inhibitor de-escalation

Continue Potent P2Y12i Full-Dose

ACTIVE COMPARATOR

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

Drug: P2Y12 inhibitor de-escalation

Interventions

P2Y12 inhibitor de-escalation 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.

CLOPIDOGREL 75 mg qd; Continue Potent P2Y12i Full-Dose; PRASUGREL 5mg qd; TICAGRELOR 60mg bid

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliera Universitaria Policlinico "G. Martino": lead
• Giampiero Vizzari: collaborator
• Giorgio Quadri: collaborator
• Greca Zanda: collaborator
• Ferdinando Varbella: collaborator
• Gianluca Di Bella: collaborator
• Antonio Micari: collaborator

Study Sites (2)

Azienda Ospedaliera Universitaria Gaetano Martino

Messina, 98125, Italy

RECRUITING

Ospedale degli Infermi

Rivoli, 10098, Italy

NOT YET RECRUITING

MeSH Terms

Conditions

Acute Coronary Syndrome; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases

Central Study Contacts

Francesco Costa, MD, PhD

CONTACT

+39090221; francesco.costa@unime.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2023
• First Posted: June 15, 2023
• Study Start: June 12, 2023
• Primary Completion: June 30, 2025
• Study Completion: October 30, 2025
• Last Updated: August 23, 2023

Record last verified: 2023-08

Locations

IT (2)