Tailoring Bleeding Reduction Approaches in Patients Undergoing PCI

Coronary Artery Disease Clinical Trial

— TAILOR BLEED  

Official title:

Tailoring Bleeding Reduction Approaches in Patients Undergoing Percutaneous Coronary Interventions: Comparative Pharmacodynamic Effects of Potent P2Y12 Inhibitor Monotherapy Versus Dual Antiplatelet Therapy De-escalation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05681702
• Other study ID #: IRB202202835
• Status: Recruiting
• Phase: Phase 4
• Start date: February 15, 2023
• Est. completion date: December 15, 2024

Study information

• Verified date: July 2023
• Source: University of Florida
• Contact: Dominick J Angiolillo, MD,PhD
• Phone: +1-904-244-3378
• Email: dominick.angiolillo[@]jax.ufl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 15, 2024
• Est. primary completion date: October 15, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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]

Related Conditions & MeSH terms

• Coronary Artery Disease
• Hemorrhage

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	University of Florida	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thrombus formation defined as AUC measured by T-TAS	Comparison of the area under the curve (AUC) determined by Total Thrombus formation Analysis System (T-TAS) between potent P2Y12 monotherapy strategy and de-escalation strategy (trough effect).	30 days