Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction

Myocardial Infarction Clinical Trial

— Dan-DAPT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05262803
• Other study ID #: 2022-500125-32-00
• Status: Recruiting
• Phase: Phase 4
• Start date: June 17, 2022
• Est. completion date: December 2028

Study information

• Verified date: March 2024
• Source: Rigshospitalet, Denmark
• Contact: Rikke Sorensen, MD, Ph.D.
• Phone: 35456851
• Email: rikke.soerensen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2808
• Est. completion date: December 2028
• Est. primary completion date: December 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemorrhage
• Infarction
• Myocardial Infarction

Intervention

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

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	The Heart Centre, Copenhagen University Hospital, Rigshospitalet	Copenhagen
Denmark	Herlev and Gentofte University Hospital - Gentofte	Hellerup
Denmark	Odense University Hospital	Odense
Denmark	Zealand University Hospital	Roskilde
Denmark	Aarhus University Hospital	Skejby

Sponsors (1)

Lead Sponsor	Collaborator
Rikke Sorensen

Country where clinical trial is conducted

Denmark, 

References & Publications (5)

Claassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Janssen PWA, Kelder JC, Postma MJ, de Boer A, Boersma C, Deneer VHM, Ten Berg JM. A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI. N Engl J Med. 2019 Oct 24;381(17):1621-1631. doi: 10.1056/NEJMoa1907096. Epub 2019 Sep 3. — View Citation

Collet JP, Thiele H, Barbato E, Barthelemy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Juni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM; ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021 Apr 7;42(14):1289-1367. doi: 10.1093/eurheartj/ehaa575. No abstract available. Erratum In: Eur Heart J. 2021 May 14;42(19):1908. Eur Heart J. 2021 May 14;42(19):1925. Eur Heart J. 2021 May 13;: Eur Heart J. 2024 Feb 1;45(5):404-405. — View Citation

Costa F, van Klaveren D, James S, Heg D, Raber L, Feres F, Pilgrim T, Hong MK, Kim HS, Colombo A, Steg PG, Zanchin T, Palmerini T, Wallentin L, Bhatt DL, Stone GW, Windecker S, Steyerberg EW, Valgimigli M; PRECISE-DAPT Study Investigators. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet. 2017 Mar 11;389(10073):1025-1034. doi: 10.1016/S0140-6736(17)30397-5. — View Citation

Jacobsen MR, Engstrom T, Torp-Pedersen C, Gislason G, Glinge C, Butt JH, Fosbol EL, Holmvang L, Pedersen F, Kober L, Jabbari R, Sorensen R. Clopidogrel, prasugrel, and ticagrelor for all-comers with ST-segment elevation myocardial infarction. Int J Cardiol. 2021 Nov 1;342:15-22. doi: 10.1016/j.ijcard.2021.07.047. Epub 2021 Jul 24. — View Citation

Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Juni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN; ESC Scientific Document Group. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur J Cardiothorac Surg. 2018 Jan 1;53(1):34-78. doi: 10.1093/ejcts/ezx334. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BARC type 2-5 bleedings	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)	1 year
Primary	NACE (Net adverse clinical events)	A composite of all-cause mortality, recurrent myocardial infarction, definite stent thrombosis, ischemic stroke, and BARC type 3-5 non-access site bleeding	1 year
Secondary	MACE (Major adverse cardiovascular events)	A composite of all-cause mortality, recurrent myocardial infarction, definite stent thrombosis and ischemic stroke	3, 6, and 12 months
Secondary	Bleedings according to BARC and TIMI (Thrombolysis in Myocardial Infarction) defintions		3, 6, and 12 months
Secondary	All-cause mortality		3, 6, and 12 months
Secondary	Non-hemorrhagic cardiovascular death		3, 6, and 12 months
Secondary	Ischemic events	Recurrent MI, definite/probable stent thrombosis, any (non-)target vessel revascularization, coronary artery bypass grafting, ischemic stroke	3, 6, and 12 months
Secondary	Discontinuation or switch to another antiplatelet drug		3, 6, and 12 months
Secondary	Pharmacoeconomic endpoint including direct and in-direct medical costs	Direct medical costs (e.g. costs for genotyping, medicinal products, re-hospitalization) and indirect costs (e.g. absence from the workforce).	3, 6, and 12 months
Secondary	Self-reported quality of life scores	Self-reported quality of life scores according to the EQ-5D-5L questionaries in electronic form	3, 6, and 12 months