Randomized, Open Label Trial of 6 Months Versus 12 Months DAPT After Drug-Eluting Stent in STEMI

Study Overview
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Brief Summary
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OBJECTIVE OF THE STUDY: To test the hypothesis that 6 months DAPT (Dual anti-platelet therapy) after second generation DES (Drug Eluting Stent) implantation in STEMI (ST elevation Myocardial Infarction) is not inferior to 12 months DAPT in terms of clinical outcomes (composite endpoint of all-cause mortality, any MI, any revascularization, stroke and major bleeding at 18 months after randomization). The trial will incorporate two registers studying respectively the safety outcomes of Bivalirudin and Prasugrel combination and Bivalirudin and Ticagrelor combination at 2 and 30 days. Finally the trial design permits assessment of the clinical outcomes after primary PCI for treatment of STEMI with the new Resolute Integrity (Medtronic Santa Rosa Ca, USA) stent at 30 days and 6 months.

Detailed Description
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BACKGROUND OF THE STUDY: First generation DES (Drug Eluting Stents) have significantly reduced the restenosis rates compared to the BMS (Bare Metal Stents) but have raised concerns regarding higher rates and ongoing propensity for stent thrombosis. Based on these concerns current guidelines advocate dual antiplatelet therapy (DAPT, aspirin plus P2Y12 inhibitor) to be continued for up to 1 year after DES implantation. Large registries analyzing recent data now challenge these recommendations and suggest no increase in mortality or (late) stent thrombosis when DAPT is discontinued after 6 months. STUDY DESIGN: This is a prospective, randomized, open-label trial testing the hypothesis that 6 months DAPT after second generation drug eluting stent (DES) implantation in STEMI is not inferior to 12 months DAPT in terms of clinical outcomes. Patients with STEMI undergoing primary PCI will be enrolled at presentation. Only those patients who are event-free (death, MI, ST, TVR/TLR or unscheduled revascularization with DES in the first 6 months and stroke or bleeding requiring discontinuation of DAPT) and on DAPT at 6 months after primary PCI will be randomized (1:1 fashion) between single (aspirin) versus dual antiplatelet therapy (aspirin plus P2Y12) for an additional 6 months (up to 12 months after primary PCI) and assessed at 18 months post randomization. STUDY POPULATION: Patients between 18 and 85 years, presenting with STEMI undergoing PCI with DES implantation. INTERVENTION: Patients, who are event-free and stil on DAPT at 6 months after primary PCI will be randomized (1:1 fashion) between single (aspirin) versus dual antiplatelet therapy (aspirin plus P2Y12) for an additional 6 months (up to 12 months after primary PCI). PRIMARY STUDY PARAMETERS/OUTCOME OF THE STUDY: DAPT STEMI trial Composite endpoint of all cause mortality, any MI, any revascularization, stroke, ST and Bleeding (TIMI) (net MACCE) at 18 months after randomization. Registry Bivalirudin/Prasugrel and Bivalirudin/Ticagrelor All cause mortality, MI, Stroke, ST and bleeding (following BARC) at 2 and 30 days. Report Resolute Integrity Primary endpoint of DAPT-STEMI, at 30 days and 6 months.

Official Title
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Prospective, Randomized, Open Label Trial of 6 Months vs. 12 Months Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction

Conditions
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Myocardial Infarction, Cardiovascular Disease

Intervention / Treatment
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* Other: 6 months DAPT
* Other: 12 months DAPT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: STEMI patients between 18-85 years who underwent primary PCI with DES implantation. Exclusion criteria enrolment: Intolerance to Aspirin, Prasugrel, Ticagrelor, Heparin, Bivalirudin, Zotarolimus or Everolimus. Known bleeding diathesis or known coagulopathy. Planned elective surgical procedure necessitating interruption of dual antiplatelet therapy during the first 6 months after randomization. History of stent thrombosis DES in main left coronary artery Active bleeding, known bleeding diathesis or known coagulopathy. Planned elective surgical procedure necessitating interruption of dual antiplatelet therapy during the first 6 months after randomization. Oral anticoagulant therapy with Coumadin derivates Malignancies or other comorbidity with a life expectancy of less than one year or that may result in protocol noncompliance Pregnancy (present, suspected or planned) or positive pregnancy test (in women with childbearing potential a negative pregnancy test is mandatory) Exclusion criteria randomization: Occurrence of death, myocardial infarction, stent thrombosis and target vessel or lesion revascularization during the first 6 months after inclusion. Stroke or bleeding requiring discontinuation of DAPT during the first 6 months after inclusion. Oral anticoagulant therapy Registry Exclusion criteria Intolerance to Prasugrel, Ticagrelor, Bivalirudin. Known bleeding diathesis or known coagulopathy Report Resolute Integrity Exclusion criteria • See exclusion criteria enrollment DAPT-STEMI protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 6 months DAPT<br>Dual antiplatelet therapy consisting of aspirin (ASA) and prasugrel or ticagrelor will be discontinued after randomisation. | Other: 6 months DAPT<br>* Dual antiplatelet therapy will be stopped at randomisation to the 6 months DAPT group. Patients will be treated from 6 months onwards only with ASA.<br>* Other names: ticagrelor, prasugrel, ASA;|
| Active Comparator: 12 months DAPT<br>Dual antiplatelet therapy consisting of aspirin (ASA) and prasugrel or ticagrelor will be continued till 12 months after enrollment in the study | Other: 12 months DAPT<br>* Dual antiplatelet therapy will be continued till 12 months after enrollment in the study<br>* Other names: ticagrelor, prasugrel, ASA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net MACCE | DAPT-STEMI trial: Composite endpoint of all cause mortality, any myocardial infarction (MI) , any revascularization, stroke and major bleeding (TIMI) (net MACCE) at 18 months after randomization | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality, MI, Stroke, ST and bleeding | Primary outcome of Registry: All cause mortality, MI, Stroke, ST and Bleeding(following BARC)at 2 days. | 2 days | 
| All cause mortality, MACCE, TIMI | DAPT-STEMI: All cause mortality, any MI, stroke, stent thrombosis (ST) and major bleeding (TIMI) at 9 months after randomization | 9 months | 
| ST definite/probable | DAPT-STEMI: ST definite/probable academic research consortium (ARC) definition at 9 months post randomization. | 9 months | 
| all cause mortality | DAPT-STEMI: All cause mortality at 9 months after randomization. | 9 months | 
| Cardiac mortality | DAPT-STEMI: Cardiac mortality at 9 months after randomization. | 9 months | 
| MI | DAPT-STEMI: Any MI at 9 months after randomization. | 9 months | 
| Target vessel MI | DAPT-STEMI: Target vessel MI at 9 months after randomization. | 9 months | 
| Bleeding | DAPT-STEMI: Bleeding at 9 months after randomization. | 9 months | 
| stroke | DAPT-STEMI: Stroke at 9 months after randomization. | 9 months | 
| Target vessel revascularization | DAPT-STEMI: Target vessel revascularization (TVR) at 9 months after randomization. | 9 months | 
| Target lesion revascularization | DAPT-STEMI: Target lesion revascularization (TLR) at 9 months after randomization. | 9 months | 
| Target vessel failure | DAPT STEMI: Target vessel failure (TVF) at 9 months after randomization. | 9 months | 
| Target lesion failure | DAPT-STEMI: Target lesion failure (TLF), at 9 months after randomization. | 9 months | 
| net MACCE | Primary endpoint of Report Resolute Integrity: Composite endpoint of all cause mortality, any myocardial infarction (MI) , any revascularization, stroke and major bleeding (TIMI) (net MACCE) at 30 days after randomization. Secondary endpoints of Report Resolute Integrity: Secondary endpoints of DAPT-STEMI at 30 days. | 30days | 
| All cause mortality, MI, Stroke, ST and bleeding | Primary outcome of registry: All cause mortality, MI,Stroke, ST and Bleeding (following BARC) at 30 days. | 30 days | 
| net MACCE | Primary endpoint of Report Resolute Integrity: Composite endpoint of all cause mortality, any myocardial infarction (MI) , any revascularization, stroke and major bleeding (TIMI) (net MACCE) at 6 months after randomization. Secondary endpoints of Report Resolute Integrity: Secondary endpoints of DAPT-STEMI at 6 monthss. | 6 months | 
| All cause mortality, MACCE, TIMI | DAPT-STEMI: All cause mortality, any MI, stroke, stent thrombosis (ST) and major bleeding (TIMI) at 18 months after randomization | 18 months | 
| ST definite/probable | DAPT-STEMI: ST definite/probable academic research consortium (ARC) definition at 18 months post randomization. | 18 months | 
| All cause mortality | DAPT-STEMI: All cause mortality at 18 months after randomization. | 18 months | 
| Cardiac mortality | DAPT-STEMI: Cardiac mortality at 18 months after randomization. | 18 months | 
| MI | DAPT-STEMI: Any MI at 18 months after randomization. | 18 months | 
| Target vessel MI | DAPT-STEMI: Target vessel MI at 18 months after randomization. | 18 months | 
| Bleeding | DAPT-STEMI: Bleeding at 18 months after randomization. | 18 months | 
| Stroke | DAPT-STEMI: Stroke at 18 months after randomization. | 18 months | 
| Target vessel revascularization | DAPT-STEMI: Target vessel revascularization (TVR) at 18 months after randomization. | 18 months | 
| Target lesion revascularization | DAPT-STEMI: Target lesion revascularization (TLR) at 18 months after randomization. | 18 months | 
| Target vessel failure | DAPT STEMI: Target vessel failure (TVF) at 18 months after randomization. | 18 months | 
| Target lesion failure | DAPT-STEMI: Target lesion failure (TLF), at 18 months after randomization. | 18 months | 
| ST following ARC | Registry: ST following ARC definition at 2 days | 2 days | 
| ST following ARC | Registry: ST following ARC definition at 30 days | 30 days | 
| All cause mortality | Registry: All cause mortality at 2 days | 2 days | 
| All cause mortality | Registry: All cause mortality at 30 days | 30 days | 
| Cardiac mortality | Registry: Cardiac Mortality at 2 days | 2 days | 
| Cardiac Mortality | Registry: Cardiac Mortality at 30 days | 30 days | 
| All MI | Registry: All MI at 2 days. | 2 days | 
| All MI | Registry: All MI at 30 days. | 30 days | 
| Target vessel MI | Registry: Target vessel MI at 2 days. | 2 days | 
| Target vessel MI | Registry: Target vessel MI at 30 days. | 30 days | 
| Bleeding BARC | Registry: Bleeding (BARC) at 2 days | 2 days | 
| Bleeding (BARC) | Registry: Bleeding (BARC) at 30 days | 30 days | 
| Stroke | Registry: Stroke at 2 days | 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DAPT- Dual Antiplatelet Therapy, STEMI