Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction

NCT ID: NCT05262803

Last Updated: 2024-03-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

2808 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-17

Study Completion Date

2028-12-31

Brief Summary

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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

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Conditions

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Myocardial Infarction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Standard-of-care DAPT

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Genotype-guided DAPT

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

Group Type EXPERIMENTAL

CYP2C19*2/*3

Intervention Type GENETIC

* 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

Shorter genotype-guided DAPT

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

Group Type EXPERIMENTAL

CYP2C19*2/*3

Intervention Type GENETIC

* 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

Shorter DAPT duration

Intervention Type OTHER

Duration of DAPT is shortened to 3 months

Interventions

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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

Intervention Type GENETIC

Shorter DAPT duration

Duration of DAPT is shortened to 3 months

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rikke Sorensen

OTHER

Sponsor Role lead

Responsible Party

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Rikke Sorensen

MD, Ph.D.

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Aalborg University Hospital

Aalborg, , Denmark

Site Status RECRUITING

The Heart Centre, Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Site Status RECRUITING

Herlev and Gentofte University Hospital - Gentofte

Hellerup, , Denmark

Site Status RECRUITING

Odense University Hospital

Odense, , Denmark

Site Status RECRUITING

Zealand University Hospital

Roskilde, , Denmark

Site Status RECRUITING

Aarhus University Hospital

Skejby, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Rikke Sorensen, MD, Ph.D.

Role: CONTACT

35456851 ext. +45

Mia R Jacobsen, MD

Role: CONTACT

35459897 ext. +45

Facility Contacts

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Phillip Freeman, BSc, MBBS, MRCP, Ph.D.

Role: primary

Rikke Sorensen, MD, Ph.D.

Role: primary

35456851 ext. +45

Mette G Charlot, MD, Ph.D.

Role: primary

Karsten T Veien, MD, DMSc

Role: primary

Henning S Kelbaek, MD, DMSc

Role: primary

Erik L Grove, Assoc.prof., MD, Ph.D.

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 29045581 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32860058 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28290994 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31479209 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34311012 (View on PubMed)

Jacobsen MR, Jabbari R, Grove EL, Maeng M, Veien K, Hougaard M, Freeman P, Kelbaek H, Charlot MG, Engstrom T, Sorensen R. Genotype-guided de-escalation and abbreviation of dual antiplatelet therapy in patients with myocardial infarction and high bleeding risk: Design and rationale of the investigator-initiated, multicenter, randomized, controlled trial, DAN-DAPT. Am Heart J. 2025 Jul;285:74-81. doi: 10.1016/j.ahj.2025.02.020. Epub 2025 Feb 26.

Reference Type DERIVED
PMID: 40015616 (View on PubMed)

Other Identifiers

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2022-500125-32-00

Identifier Type: -

Identifier Source: org_study_id

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