Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction

NCT05262803 | Recruiting Phase 4 DMC

• 1 other identifier: 2022-500125-32-00
• Study Type: interventional
• Target: 2,808
• Locations: 1 country
• Sites: 6

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.

Conditions

Myocardial Infarction

Keywords

High bleeding risk; CYP2C19 genotyping; Dual antiplatelet therapy; Percutaneous coronary intervention

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (8)

• MACE (Major adverse cardiovascular events)

  3, 6, and 12 months

• 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

Study Arms (3)

Standard-of-care DAPT

NO INTERVENTION

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

Genotype-guided DAPT

EXPERIMENTAL

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

Genetic: CYP2C19*2/*3

Shorter genotype-guided DAPT

EXPERIMENTAL

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

Genetic: CYP2C19*2/*3; Other: Shorter DAPT duration

Interventions

CYP2C19*2/*3 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

Genotype-guided DAPT; Shorter genotype-guided DAPT

Shorter DAPT duration OTHER

Duration of DAPT is shortened to 3 months

Shorter genotype-guided DAPT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rikke Sorensen: lead

Study Sites (6)

Aalborg University Hospital

Aalborg, 9000, Denmark

RECRUITING

The Heart Centre, Copenhagen University Hospital, Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Herlev and Gentofte University Hospital - Gentofte

Hellerup, 2900, Denmark

RECRUITING

Odense University Hospital

Odense, 5000, Denmark

RECRUITING

Zealand University Hospital

Roskilde, 4000, Denmark

RECRUITING

Aarhus University Hospital

Skejby, 8200, Denmark

RECRUITING

Related Publications (6)

• 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.

  PMID: 29045581 BACKGROUND

• 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.

  PMID: 32860058 BACKGROUND

• 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.

  PMID: 28290994 BACKGROUND

• 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.

  PMID: 31479209 BACKGROUND

• 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.

  PMID: 34311012 BACKGROUND

• 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.

  PMID: 40015616 DERIVED

MeSH Terms

Conditions

Myocardial Infarction

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Central Study Contacts

Rikke Sorensen, MD, Ph.D.

CONTACT

35456851; rikke.soerensen@regionh.dk

Mia R Jacobsen, MD

CONTACT

35459897; mia.ravn.jacobsen@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Ph.D.

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: March 2, 2022
• Study Start: June 17, 2022
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 15, 2024

Record last verified: 2024-03

Locations

DK (6)