Dan-DAPT: Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction

Sponsor

Rikke Sorensen (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05262803

Collaborator

(none)

2,808

Enrollment

Locations

Arms

Anticipated Duration (Months)

468

Patients Per Site

11.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Genetic: CYP2C192/3 Other: Shorter DAPT duration	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2808 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction Treated With Percutaneous Coronary Intervention - The Dan-DAPT Trial

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Standard-of-care DAPT Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and prasugrel or ticagrelor for 6 months followed by ASA monotherapy.
Experimental: Genotype-guided DAPT DAPT according to CYP2C192/3-genotyping for 6 months followed by ASA monotherapy.	Genetic: *CYP2C192/3* Non-carriers of CYP2C192/3 loss-of-function alleles: DAPT with clopidogrel and ASA Carriers of CYP2C192/3 loss-of-function alleles: DAPT with prasugrel (or ticagrelor) and ASA
Experimental: Shorter genotype-guided DAPT DAPT according to CYP2C192/3-genotyping for 3 months followed by ASA monotherapy.	Genetic: *CYP2C192/3* Non-carriers of CYP2C192/3 loss-of-function alleles: DAPT with clopidogrel and ASA Carriers of CYP2C192/3 loss-of-function alleles: DAPT with prasugrel (or ticagrelor) and ASA Other: Shorter DAPT duration Duration of DAPT is shortened to 3 months

Arm

Intervention/Treatment

No Intervention: Standard-of-care DAPT

Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and prasugrel or ticagrelor for 6 months followed by ASA monotherapy.

Experimental: Genotype-guided DAPT

DAPT according to CYP2C19*2/*3-genotyping for 6 months followed by ASA monotherapy.

Genetic: CYP2C19*2/*3

Non-carriers of CYP2C19*2/*3 loss-of-function alleles: DAPT with clopidogrel and ASA Carriers of CYP2C19*2/*3 loss-of-function alleles: DAPT with prasugrel (or ticagrelor) and ASA

Experimental: Shorter genotype-guided DAPT

DAPT according to CYP2C19*2/*3-genotyping for 3 months followed by ASA monotherapy.

Genetic: CYP2C19*2/*3

Non-carriers of CYP2C19*2/*3 loss-of-function alleles: DAPT with clopidogrel and ASA Carriers of CYP2C19*2/*3 loss-of-function alleles: DAPT with prasugrel (or ticagrelor) and ASA

Other: Shorter DAPT duration

Duration of DAPT is shortened to 3 months

Outcome Measures

Primary Outcome Measures

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
MACE (Major cardiovascular events) [1 year]
A composite of all-cause mortality, recurrent myocardial infarction (MI), definite stent thrombosis, and ischemic stroke

Secondary Outcome Measures

Bleedings according to BARC and TIMI (Thrombolysis in Myocardial Infarction) defintions [3, 6, and 12 months]
All-cause mortality [3, 6, and 12 months]
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
Discontinuation or switch to another antiplatelet drug [3, 6, and 12 months]
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).
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

PRECISE-DAPT score ≥25
Age ≥18 years

Exclusion Criteria:

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

120 mmHg)

Unable to understand and follow study-related instructions or to comply with study protocol

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Aalborg University Hospital	Aalborg	Denmark	9000
2	The Heart Centre, Copenhagen University Hospital, Rigshospitalet	Copenhagen	Denmark	2100
3	Herlev and Gentofte University Hospital - Gentofte	Hellerup	Denmark	2900
4	Odense University Hospital	Odense	Denmark	5000
5	Zealand University Hospital	Roskilde	Denmark	4000
6	Aarhus University Hospital	Skejby	Denmark	8200