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

Primary Purpose

Myocardial Infarction

Status
Recruiting
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
CYP2C19*2/*3
Shorter DAPT duration
Sponsored by
Rikke Sorensen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myocardial Infarction focused on measuring High bleeding risk, CYP2C19 genotyping, Dual antiplatelet therapy, Percutaneous coronary intervention

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Aalborg University Hospital
  • The Heart Centre, Copenhagen University Hospital, RigshospitaletRecruiting
  • Herlev and Gentofte University Hospital - Gentofte
  • Odense University Hospital
  • Zealand University Hospital
  • Aarhus University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Experimental

Arm Label

Standard-of-care DAPT

Genotype-guided DAPT

Shorter genotype-guided DAPT

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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)
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
MACE (Major cardiovascular events)
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
All-cause mortality
Non-hemorrhagic cardiovascular death
Ischemic events
Recurrent MI, definite/probable stent thrombosis, any (non-)target vessel revascularization, coronary artery bypass grafting, ischemic stroke
Discontinuation or switch to another antiplatelet drug
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).
Self-reported quality of life scores
Self-reported quality of life scores according to the EQ-5D-5L questionaries in electronic form

Full Information

First Posted
February 9, 2022
Last Updated
October 25, 2022
Sponsor
Rikke Sorensen
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1. Study Identification

Unique Protocol Identification Number
NCT05262803
Brief Title
Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction
Acronym
Dan-DAPT
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

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 17, 2022 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Rikke Sorensen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction
Keywords
High bleeding risk, CYP2C19 genotyping, Dual antiplatelet therapy, Percutaneous coronary intervention

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
2808 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard-of-care DAPT
Arm Type
No Intervention
Arm Description
Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and prasugrel or ticagrelor for 6 months followed by ASA monotherapy.
Arm Title
Genotype-guided DAPT
Arm Type
Experimental
Arm Description
DAPT according to CYP2C19*2/*3-genotyping for 6 months followed by ASA monotherapy.
Arm Title
Shorter genotype-guided DAPT
Arm Type
Experimental
Arm Description
DAPT according to CYP2C19*2/*3-genotyping for 3 months followed by ASA monotherapy.
Intervention Type
Genetic
Intervention Name(s)
CYP2C19*2/*3
Intervention Description
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
Other
Intervention Name(s)
Shorter DAPT duration
Intervention Description
Duration of DAPT is shortened to 3 months
Primary Outcome Measure Information:
Title
BARC type 2-5 bleedings
Description
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)
Time Frame
1 year
Title
NACE (Net adverse clinical events)
Description
A composite of all-cause mortality, recurrent myocardial infarction, definite stent thrombosis, ischemic stroke, and BARC type 3-5 non-access site bleeding
Time Frame
1 year
Title
MACE (Major cardiovascular events)
Description
A composite of all-cause mortality, recurrent myocardial infarction (MI), definite stent thrombosis, and ischemic stroke
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Bleedings according to BARC and TIMI (Thrombolysis in Myocardial Infarction) defintions
Time Frame
3, 6, and 12 months
Title
All-cause mortality
Time Frame
3, 6, and 12 months
Title
Non-hemorrhagic cardiovascular death
Time Frame
3, 6, and 12 months
Title
Ischemic events
Description
Recurrent MI, definite/probable stent thrombosis, any (non-)target vessel revascularization, coronary artery bypass grafting, ischemic stroke
Time Frame
3, 6, and 12 months
Title
Discontinuation or switch to another antiplatelet drug
Time Frame
3, 6, and 12 months
Title
Pharmacoeconomic endpoint including direct and in-direct medical costs
Description
Direct medical costs (e.g. costs for genotyping, medicinal products, re-hospitalization) and indirect costs (e.g. absence from the workforce).
Time Frame
3, 6, and 12 months
Title
Self-reported quality of life scores
Description
Self-reported quality of life scores according to the EQ-5D-5L questionaries in electronic form
Time Frame
3, 6, and 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rikke Sorensen, MD, Ph.D.
Phone
35456851
Ext
+45
Email
rikke.soerensen@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Mia R Jacobsen, MD
Phone
35459897
Ext
+45
Email
mia.ravn.jacobsen@regionh.dk
Facility Information:
Facility Name
Aalborg University Hospital
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Phillip Freeman, BSc, MBBS, MRCP, Ph.D.
Facility Name
The Heart Centre, Copenhagen University Hospital, Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rikke Sorensen, MD, Ph.D.
Phone
35456851
Ext
+45
Email
rikke.soerensen@regionh.dk
First Name & Middle Initial & Last Name & Degree
Rikke Sorensen, MD, Ph.D.
First Name & Middle Initial & Last Name & Degree
Mia R Jacobsen, MD
First Name & Middle Initial & Last Name & Degree
Jabbari Jabbari, MD, Ph.D.
First Name & Middle Initial & Last Name & Degree
Thomas Engstrom, Prof., MD, Ph.D., DMSc
Facility Name
Herlev and Gentofte University Hospital - Gentofte
City
Hellerup
ZIP/Postal Code
2900
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mette G Charlot, MD, Ph.D.
Facility Name
Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karsten T Veien, MD, DMSc
Facility Name
Zealand University Hospital
City
Roskilde
ZIP/Postal Code
4000
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Henning S Kelbaek, MD, DMSc
Facility Name
Aarhus University Hospital
City
Skejby
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erik L Grove, Assoc.prof., MD, Ph.D.
First Name & Middle Initial & Last Name & Degree
Erik L Grove, Assoc. prof., MD, Ph.D
First Name & Middle Initial & Last Name & Degree
Michael Maeng, Assoc. prof., MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
29045581
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.
Results Reference
background
PubMed Identifier
32860058
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;:
Results Reference
background
PubMed Identifier
28290994
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.
Results Reference
background
PubMed Identifier
31479209
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.
Results Reference
background
PubMed Identifier
34311012
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.
Results Reference
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Reduced Antithrombotic Strategy for High Bleeding Risk Patients With Myocardial Infarction

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