Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction

Phase 4

Recruiting

• Conditions: Myocardial Infarction
• Interventions: Genetic: CYP2C19*2/*3; Other: Shorter DAPT duration

• Registration Number: NCT05262803
• Lead Sponsor: Rikke Sorensen

Brief Summary

Rationale: Heart attacks are a major cause of death and result from coronary blood clots that require acute coronary intervention and antithrombotic drugs to restore blood flow and prevent new heart attacks. Over time, more potent antithrombotic drugs have been introduced like prasugrel and ticagrelor. These drugs have replaced the older drug, clopidogrel, as approximately 30% of patients are low-responders to clopidogrel for genetic reasons. However, the newer drugs introduce a significant risk of serious bleeding.

Aim: The aim of this trial is to assess a reduced antithrombotic strategy for high bleeding risk patients with heart attacks to reduce bleeding safely.

Hypothesis: Significantly reduced bleeding with a similar preventive effect are expected.

Design: The Dan-DAPT trial include high bleeding risk patients with heart attacks from Danish hospitals (Rigshospitalet, Aarhus, Odense, Aalborg, Roskilde, and Gentofte hospital) and randomize them to standard-of-care or shorter and individualized antithrombotic therapy based on responsiveness to clopidogrel after genetic testing.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-02-09
• Study First Submitted QC: 2022-02-21
• Study First Posted: 2022-03-02
• Study Start: 2022-06-17
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-12
• Last Update Posted: 2024-03-15
• Primary Completion: 2028-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2808

Inclusion Criteria

1. MI caused by atherothrombotic CAD (Type 1 MI) according to "The Fourth Universal Definition of MI", which has been treated with PCI with contemporary drug-eluting stents. This definition of type 1 MI requires the detection of a rise and/or fall of cardiac troponin values with at least one value >99th percentile and at least one of the following criteria assessed by the treating physician:

   • symptoms indicating acute myocardial ischemia
   • new ischemic changes on the electrocardiogram
   • development of pathological Q-waves
   • imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology
   • visible coronary thrombus by angiography

2. PRECISE-DAPT score ≥25

3. Age ≥18 years

Exclusion Criteria

1. Contraindications including allergies to ASA or P2Y12 inhibitors
2. Indication for oral anticoagulation
3. Previous stent thrombosis
4. Life expectancy <1 year
5. Resuscitated cardiac arrest with Glasgow Coma Scale <8 and/or need of intubation
6. Prior intracranial hemorrhage
7. Active bleeding (BARC ≥2) at randomization
8. Women who are pregnant, have given birth recently (within the past 90 days), are lactating, or are fertile without contraception
9. Hypertensive crisis (systolic blood pressure >180 mmHg and/or diastolic blood pressure >120 mmHg)
10. Unable to understand and follow study-related instructions or to comply with study protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Shorter genotype-guided DAPT	Shorter DAPT duration	DAPT according to CYP2C19\*2/\*3-genotyping for 3 months followed by ASA monotherapy.
Shorter genotype-guided DAPT	CYP2C19*2/*3	DAPT according to CYP2C19\*2/\*3-genotyping for 3 months followed by ASA monotherapy.
Genotype-guided DAPT	CYP2C19*2/*3	DAPT according to CYP2C19\*2/\*3-genotyping for 6 months followed by ASA monotherapy.

Primary Outcome Measures

Name	Time	Method
BARC type 2-5 bleedings	1 year	A composite of type 2-5 non-access site bleeding according to the Bleeding Academic Research Consortium (BARC) scale, ranging from bleedings that require diagnosis, hospitalization, or treatment by a health care professional (BARC type 2) to fatal bleedings (BARC type 5)
NACE (Net adverse clinical events)	1 year	A composite of all-cause mortality, recurrent myocardial infarction, definite stent thrombosis, ischemic stroke, and BARC type 3-5 non-access site bleeding

Secondary Outcome Measures

Name	Time	Method
All-cause mortality	3, 6, and 12 months
MACE (Major adverse cardiovascular events)	3, 6, and 12 months	A composite of all-cause mortality, recurrent myocardial infarction, definite stent thrombosis and ischemic stroke
Non-hemorrhagic cardiovascular death	3, 6, and 12 months
Ischemic events	3, 6, and 12 months	Recurrent MI, definite/probable stent thrombosis, any (non-)target vessel revascularization, coronary artery bypass grafting, ischemic stroke
Pharmacoeconomic endpoint including direct and in-direct medical costs	3, 6, and 12 months	Direct medical costs (e.g. costs for genotyping, medicinal products, re-hospitalization) and indirect costs (e.g. absence from the workforce).
Discontinuation or switch to another antiplatelet drug	3, 6, and 12 months
Bleedings according to BARC and TIMI (Thrombolysis in Myocardial Infarction) defintions	3, 6, and 12 months
Self-reported quality of life scores	3, 6, and 12 months	Self-reported quality of life scores according to the EQ-5D-5L questionaries in electronic form

Trial Locations

Locations (6)

Aalborg University Hospital; 🇩🇰 Aalborg, Denmark

The Heart Centre, Copenhagen University Hospital, Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Herlev and Gentofte University Hospital - Gentofte; 🇩🇰 Hellerup, Denmark

Aarhus University Hospital; 🇩🇰 Skejby, Denmark

Zealand University Hospital; 🇩🇰 Roskilde, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark