Assessment of an Early De-Escalation to a Low-potency Single Antiplatelet Therapy Guided by Genetics Versus a Systematic High-Potency Single Antiplatelet Therapy to Neutralize Bleeding Complications in Patients With High Bleeding Risk Beyond One Month After an Acute Coronary Syndrome

NCT05577988 | Recruiting Phase 3 DMC

• 2 other identifiers: APHP21102720-0570 PHRC
• Study Type: interventional
• Target: 2,468
• Locations: 1 country
• Sites: 1

Brief Summary

Patients who suffered from acute coronary syndrome (ACS) are usually treated with a long-term dual antiplatelet therapy (DAPT) to reduce stent thrombosis and recurrent ischemic event. Nonetheless, recent important data have demonstrated the efficacy of a short term DAPT and an early single antiplatelet therapy in high bleeding and ischemic risk patients. The bleeding risk is associated with a significant mortality. This risk is especially high in patients treated with potent P2Y12 inhibitors like ticagrelor or prasugrel after an ACS. As a result of the abounding data regarding the safety of an early single antiplatelet therapy with high potency antiplatelet therapy (ticagrelor or prasugrel), it is likely that such strategy will soon be implemented in the guidelines. The benefits of these high-potency P2Y12 inhibitors over clopidogrel mostly occur in patients with genetic polymorphisms of CYP2Y12 associated with a loss of function in clopidogrel metabolism. Furthermore, the anti-ischemic benefit of potent P2Y12 inhibitors over clopidogrel occurs early, while excess bleeding events often arise during chronic treatment. Our hypothesis is that a systematic and rapid genetic screening of CYP2C90 \*2 or \*17 polymorphism to guide an early single therapy with low potency antiplatelet (aspirin or clopidogrel) could lead to less bleeding events with a consistent efficacy towards cardiac events compared with high potency antiplatelet therapies (prasugrel or ticagrelor) in high bleeding risk patients treated for ACS.

Conditions

MYOCARDIAL INFARCTION

Keywords

Acute Coronary Syndrome; High Bleeding Risk; Antiplatelet Therapy

Outcome Measures

Primary Outcomes (1)

• Rate of combinated major and minor bleeding events (BARC 2 to 5 BARC)

  the occurrence of major or minor bleeding events between randomization to one of the de-escalation strategies and 1 year after index ACS defined according to the Bleeding Academic Research Consortium (BARC) classification as type 2 to 5

  From randomization (1-3months after inclusion) to 1year after inclusion

Secondary Outcomes (3)

• Rate of major adverse cardiovascular events

  From randomization to de-escalation (1-3months) to 1year

• Rate of major bleeding events

  randomization to de-escalation (1-3months) to 1year

• Rate of minor bleeding events

  randomization to de-escalation (1-3months) to 1year

Study Arms (2)

Control arm

NO INTERVENTION

Standard of Care : Systematic de-escalation to a high potency antiplatelet single therapy

Intervention arm

OTHER

single-antiplatelet with a low-potency antiplatelet (aspirin or clopidogrel) guided by genetic testing.

Other: single-antiplatelet with a low-potency antiplatelet (aspirin or clopidogrel) guided by genetic testing.

Interventions

single-antiplatelet with a low-potency antiplatelet (aspirin or clopidogrel) guided by genetic testing. OTHER

* Individuals without genetic loss of function to metabolize clopidogrel (\*1/\*1, \*2/\*17, \*3/\*17): stop DAPT and switch to a single antiplatelet therapy by clopidogrel. * Individuals with genetic loss of function to metabolize clopidogrel (\*2/\*3, 1/\*3, \*2/\*2, \*1/\*2,\*3/\*3): stop potent P2Y12 inhibitor and treat with a single antiplatelet therapy by aspirin. * Individuals with fast metabolization of clopidogrel (\*1/\*17 or \*17/\*17): stop potent P2Y12 inhibitor and treat with a single antiplatelet therapy by aspirin.

Intervention arm

Eligibility Criteria

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

You may qualify if:

• Being 18-year-old or older
• Admission for type 1 acute myocardial infarction (STEMI or NSTEMI)
• Bedside genetic testing for clopidogrel resistance that can be performed during hospital stay for ACS (oral swab kit with result within 1 hour)
• Treated with aspirin and ticagrelor, or aspirin and prasugrel at the screening phase and at the randomization visit.
• High bleeding risk as defined below (criteria adapted from the Consensus Document From the Academic Research Consortium for High Bleeding Risk) (at least one criterion) :
• Age ≥75 years old.
• Baseline haemoglobin \<11 g/dl (or anaemia requiring transfusion during the 4 weeks prior to randomization).
• Chronic Kidney Disease with estimated glomerular filtration rate ≤ 30 ml/min.
• Thrombocytopenia with platelet count \< 100 x 109 / L
• Chronic bleeding diatheses: inherited or acquired conditions known to be associated with increased bleeding risk such as platelet dysfunction, von Willebrand disease (prevalence of 1%-2% in the general population), inherited or acquired clotting factor deficiencies (including factors VII, VIII \[hemophilia A\], IX \[hemophilia B\], and XI), or acquired antibodies to clotting factors, among others.
• Cirrhosis with portal hypertension.
• PCI after major traumatism or surgery.
• Any documented stroke in the last 12 months.
• Hospital admission for bleeding or transfusion within last 6 months.
• Nonskin cancer diagnosed or treated ≤3 years.

You may not qualify if:

• Currently participating in any interventional investigational device or drug trial
• Any prior documented intracerebral bleed
• Contra-indication, known allergy or expected interactions with clopidogrel. Baseline treatment (at screening) should not include an antiplatelet therapy for which a contra-indication, known allergy or expected interactions is known (example history of stroke and use of prasugrel, or concomitant use of ticagrelor and ritonavir)
• Patients on concomitant treatment with an anticoagulant agent (Vitamin-K antagonists or novel oral anticoagulants such as rivaroxaban, dabigatran or apixaban)
• Planned surgery within 12 coming months
• Patient under guardianship or curatorship
• Pregnancy or breastfeeding
• Inability to sign the informed consent form

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Fonds de Dotation ACTION: collaborator

Study Sites (1)

Hopital Pitié Salpetrière

Paris, IDF, 75013, France

RECRUITING

MeSH Terms

Conditions

Myocardial Infarction; Acute Coronary Syndrome

Interventions

Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Michel ZEITOUNI, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY CHAIR

Central Study Contacts

Michel ZEITOUNI, MD,PhD

CONTACT

33142165535; michel.zeitouni@aphp.fr

Delphine BRUGIER, PhD

CONTACT

33142162918; delphine.brugier-ext@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Members of the Endpoint Adjudication Committee (AEC) are blinded to randomization group, treatments and characteristics. The Committee will assess all endpoints according to the definitions stated in the protocol. This will be a blinded evaluation. Clinical endpoint adjudication will be performed using blinded source data that are provided by CRAs to the committee.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: National, multicentre, comparative, controlled, randomized, open label trial using the PROBE study design (Prospective Randomized Open Blinded End-point)

Study Record Dates

• First Submitted: October 10, 2022
• First Posted: October 13, 2022
• Study Start: June 18, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: January 16, 2026

Record last verified: 2026-01

Locations

FR (1)