Tailoring Bleeding Reduction Approaches in Patients Undergoing PCI

NCT ID: NCT05681702

Last Updated: 2025-11-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-15
• Study Completion Date: 2026-03-31

Brief Summary

Two strategies have both proven to be effective in reducing bleeding complications while preserving efficacy compared with maintaining long-term DAPT with aspirin and a potent P2Y12 inhibitor: a) DAPT de-escalation (i.e., switching from prasugrel or ticagrelor to clopidogrel while maintaining aspirin) and b) potent P2Y12 inhibitor monotherapy (i.e., maintaining prasugrel or ticagrelor and dropping aspirin). These strategies have been tested in a number of trials and have led to changes in practice guidelines to consider either one of these strategies as bleeding reduction approaches among ACS patients undergoing PCI. However, comparative assessments between DAPT de-escalation and potent P2Y12 inhibitor monotherapy are lacking.

Detailed Description

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor represents the standard of care for the prevention of atherothrombotic events in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). In particular, in ACS patients undergoing PCI, DAPT is initiated during the index event and maintained for up to 12 months to prevent stent-related complications as well as ischemic recurrences in non-treated coronary segments. Three oral P2Y12 inhibitors are currently recommended in this setting: clopidogrel, prasugrel, and ticagrelor. However, in ACS patients undergoing PCI, prasugrel and ticagrelor are preferred over clopidogrel based on results of large-scale clinical trials showing their superior reduction in ischemic events, including stent thrombosis. Nevertheless, such ischemic benefit occurs at the expense of increased bleeding. These observations are attributed to the greater antiplatelet potency of prasugrel and ticagrelor over clopidogrel. Importantly, accruing evidence support that bleeding complications carry significant prognostic implications, including increased mortality, underscoring the need to define antiplatelet strategies associated with reduced bleeding while preserving ischemic efficacy. The notion that most recurrent ischemic events, including stent thrombosis, occur early after the index event (i.e., 1-3 months post PCI) has prompted the design of clinical trials assessing antiplatelet treatment regimens consisting in the use of agents with enhanced platelet inhibition during the first months after PCI followed by approaches with reduced platelet inhibition. To this extent, two strategies have both proven to be effective in reducing bleeding complications while preserving efficacy compared with maintaining long-term DAPT with aspirin and a potent P2Y12 inhibitor: a) DAPT de-escalation (i.e., switching from prasugrel or ticagrelor to clopidogrel while maintaining aspirin) and b) potent P2Y12 inhibitor monotherapy (i.e., maintaining prasugrel or ticagrelor and dropping aspirin). These strategies have been tested in a number of trials and have led to changes in practice guidelines to consider either one of these strategies as bleeding reduction approaches among ACS patients undergoing PCI. However, comparative assessments between DAPT de-escalation and potent P2Y12 inhibitor monotherapy are lacking.

Conditions

Coronary Artery Disease

Keywords

Percutaneous coronary intervention; Dual antiplatelet therapy; Bleeding

Study Design

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

Study Groups

DAPT de-escalation

Aspirin 81-mg od and clopidogrel 75-mg qd.

Group Type: ACTIVE_COMPARATOR

aspirin plus clopidogrel

Intervention Type: DRUG

After at least 30 days of DAPT \[with aspirin 81-mg od and a potent P2Y12 inhibitor (prasugrel 10 mg od or ticagrelor 90-mg BID)\] in chronic coronary syndrome or after at least 90 days of DAPT in acute coronary syndromes; patients will continue aspirin and switch to clopidogrel 75-mg.

Potent P2Y12 monotherapy

Potent P2Y12 inhibitor with prasugrel 10 mg od or ticagrelor 90 mg BID.

Group Type: EXPERIMENTAL

prasugrel or ticagrelor

Intervention Type: DRUG

After at least 30 days of DAPT \[with aspirin 81-mg od and a potent P2Y12 inhibitor (prasugrel 10 mg od or ticagrelor 90-mg BID)\] in chronic coronary syndrome or after at least 90 days of DAPT in acute coronary syndromes; patients will drop aspirin and continue prasugrel or ticagrelor.

Interventions

aspirin plus clopidogrel

After at least 30 days of DAPT \[with aspirin 81-mg od and a potent P2Y12 inhibitor (prasugrel 10 mg od or ticagrelor 90-mg BID)\] in chronic coronary syndrome or after at least 90 days of DAPT in acute coronary syndromes; patients will continue aspirin and switch to clopidogrel 75-mg.

Intervention Type: DRUG

prasugrel or ticagrelor

After at least 30 days of DAPT \[with aspirin 81-mg od and a potent P2Y12 inhibitor (prasugrel 10 mg od or ticagrelor 90-mg BID)\] in chronic coronary syndrome or after at least 90 days of DAPT in acute coronary syndromes; patients will drop aspirin and continue prasugrel or ticagrelor.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients who presented with chronic coronary syndrome, underwent PCI and have been on maintenance treatment with DAPT, composed of low-dose aspirin (81mg od) and prasugrel (10 mg od) or ticagrelor (90 mg bid) for at least 30 days. Or patients that presented with an Acute coronary syndrome (ACS) event and underwent PCI and have been on maintenance treatment with DAPT, composed of low-dose aspirin (81mg od) and prasugrel (10mg od) or ticagrelor (90mg bid) for 3 months or greater.

2. Age ≥18 years old

3. Provide written informed consent

Exclusion Criteria

1. Prior history of stent thrombosis

2. On treatment with any oral anticoagulant (vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban) or chronic low-molecular-weight heparin (at venous thrombosis treatment, not for prophylaxis)

3. Renal failure requiring dialysis

4. Patients with known bleeding diathesis or coagulation disorders

5. Known severe hepatic impairment

6. Hemodynamic instability

7. Hypersensitivity to clopidogrel

8. Pregnant and breastfeeding women [women of childbearing age must use reliable birth control (i.e., oral contraceptives) while participating in the study]

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominick J Angiolillo, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University of Florida College of Medicine Jacksonville

Locations

University of Florida

Jacksonville, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Dominick J Angiolillo, MD,PhD

Role: CONTACT

Phone: +1-904-244-3378

Email: dominick.angiolillo@jax.ufl.edu

Andrea Burton, MPH, CCRP

Role: CONTACT

Phone: +1-904-244-5617

Email: Andrea.Burton@jax.ufl.edu

Facility Contacts

Dominick J Angiolillo, MD, PhD

Role: primary

References

Capodanno D, Baber U, Bhatt DL, Collet JP, Dangas G, Franchi F, Gibson CM, Gwon HC, Kastrati A, Kimura T, Lemos PA, Lopes RD, Mehran R, O'Donoghue ML, Rao SV, Rollini F, Serruys PW, Steg PG, Storey RF, Valgimigli M, Vranckx P, Watanabe H, Windecker S, Angiolillo DJ. P2Y12 inhibitor monotherapy in patients undergoing percutaneous coronary intervention. Nat Rev Cardiol. 2022 Dec;19(12):829-844. doi: 10.1038/s41569-022-00725-6. Epub 2022 Jun 13.

Reference Type: BACKGROUND

PMID: 35697777 (View on PubMed)

Capodanno D, Bhatt DL, Gibson CM, James S, Kimura T, Mehran R, Rao SV, Steg PG, Urban P, Valgimigli M, Windecker S, Angiolillo DJ. Bleeding avoidance strategies in percutaneous coronary intervention. Nat Rev Cardiol. 2022 Feb;19(2):117-132. doi: 10.1038/s41569-021-00598-1. Epub 2021 Aug 23.

Reference Type: BACKGROUND

PMID: 34426673 (View on PubMed)

Other Identifiers

IRB202202835

Identifier Type: -

Identifier Source: org_study_id