Clinical trial NCT05262803: Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction
Official title: Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction Treated With Percutaneous Coronary Intervention - The Dan-DAPT Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Myocardial Infarction
Keywords: High bleeding risk
CYP2C19 genotyping
Dual antiplatelet therapy
Percutaneous coronary intervention
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2022-03-02
Enrollment: 2808
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: BARC type 2-5 bleedings
timeFrame: 1 year
measure: NACE (Net adverse clinical events)
timeFrame: 1 year
Secondary outcomes:
measure: MACE (Major adverse cardiovascular events)
timeFrame: 3, 6, and 12 months
measure: Bleedings according to BARC and TIMI (Thrombolysis in Myocardial Infarction) defintions
timeFrame: 3, 6, and 12 months
measure: All-cause mortality
timeFrame: 3, 6, and 12 months
measure: Non-hemorrhagic cardiovascular death
timeFrame: 3, 6, and 12 months
measure: Ischemic events
timeFrame: 3, 6, and 12 months
measure: Discontinuation or switch to another antiplatelet drug
timeFrame: 3, 6, and 12 months
measure: Pharmacoeconomic endpoint including direct and in-direct medical costs
timeFrame: 3, 6, and 12 months
measure: Self-reported quality of life scores
timeFrame: 3, 6, and 12 months
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Copenhagen
country: Denmark
facility: The Heart Centre, Copenhagen University Hospital, Rigshospitalet
city: Hellerup
country: Denmark
facility: Herlev and Gentofte University Hospital - Gentofte
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Zealand University Hospital
city: Skejby
country: Denmark
facility: Aarhus University Hospital
Study officials:
References:
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.
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.
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.
citation: 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.
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.