Evaluating a genetic-guided low-potency antiplatelet therapy for high bleeding risk patients after heart attacks

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

This study tests if using a low-potency heart medication based on genetic testing can help patients at high risk of bleeding after a heart attack feel safer than using a stronger medication.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2468 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 1 site (Paris, IDF)
• Trial ID: NCT05577988 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of an early de-escalation to a low-potency single antiplatelet therapy, guided by genetic testing, compared to a systematic high-potency single antiplatelet therapy in patients at high risk of bleeding following an acute coronary syndrome. The study employs a multicenter, randomized, open-label design, with participants stratified based on their revascularization status and genetic profiles. Patients will be randomized 1 to 3 months after their acute coronary event to receive either a high-potency antiplatelet or a low-potency antiplatelet based on their genetic testing results. The goal is to minimize bleeding complications while maintaining effective treatment for heart conditions.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older who have experienced a type 1 acute myocardial infarction and are at high risk for bleeding.

Not a fit: Patients who do not meet the high bleeding risk criteria or those who have not experienced an acute coronary syndrome may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce bleeding complications in high-risk patients while still providing effective antiplatelet therapy.

How similar studies have performed: Other studies have shown promising results with genetic-guided antiplatelet therapy, suggesting that this approach may be effective in managing bleeding risks.

Eligibility criteria

Inclusion Criteria:

* 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.
  * Planned daily nonsteroidal anti-inflammatory drugs (other than aspirin) or steroids for ≥30 days after PCI.
* patient affiliated to a social security system
* signed informed consent form
* Women of childbearing capacity with effective contraception for the duration of the research OR man, OR woman not of childbearing capacity

Exclusion Criteria:

* 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

Where this trial is running

Paris, IDF

• Hopital Pitié Salpetrière — Paris, Idf, France (Recruiting)

Study contacts

• Study coordinator: Michel ZEITOUNI, MD,PhD

Conditions MYOCARDIAL INFARCTION; Acute Coronary Syndrome; High Bleeding Risk; Antiplatelet Therapy