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

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

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Cardiovascular Disease
• Intervention / Treatment: Other: 6 months DAPT; Other: 12 months DAPT

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum
  • Breda, Netherlands, 4818CK
    • Amphia Ziekenhuis
  • Enschede, Netherlands
    • Medisch Spectrum Twente
  • Heerlen, Netherlands
    • Atrium MC Parkstad
  • Rotterdam, Netherlands
    • Erasmus MC
  • Rotterdam, Netherlands, 3079DZ
    • Maasstadhospital
  • The Hague, Netherlands, 2512VA
    • Haga Hospital
  • Zwolle, Netherlands
    • Isala Clinics
• Norway
  • Oslo, Norway
    • Oslo University Hospital
• Poland
  • Bielsko-Biala, Poland, 43316
    • Amerykańskie Kliniki Serca
  • Chrzanów, Poland, 32500
    • Małopolskie Centrum Sercowo-Naczyniowe PAKS
  • Dąbrowa Górnicza, Poland, 41300
    • Polsko-Amerykańskie Kliniki Serca
  • Kedzierzyn Kozle, Poland
    • Polsko_Amerykanskei Kliniki Serca
  • Krakow, Poland
    • University Hospital in Krakow
  • Nysa, Poland
    • Polsko_Amerykanskei Kliniki Serca
• Switzerland
  • Fribourg, Switzerland, 1708
    • Hopital cantonal Fribourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 6 months DAPT; Dual antiplatelet therapy consisting of aspirin (ASA) and prasugrel or ticagrelor will be discontinued after randomisation.	Other: 6 months DAPT; 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.; Other Names: ticagrelor, prasugrel, ASA
Active Comparator: 12 months DAPT; 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; Dual antiplatelet therapy will be continued till 12 months after enrollment in the study; Other Names: ticagrelor, prasugrel, ASA

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maasstad Hospital
• Collaborators: Medtronic
• Investigators: Principal Investigator: Elvin Kedhi, MD PHD, Isala; Principal Investigator: Martin van der Ent, MD PhD, Maasstadhospital / MCR B.V.; Study Chair: Clemens von Birgelen, MD PhD, Medisch Spectrum Twente; Study Chair: Felix Zijlstra, MD PhD, Erasmus Medisch Centrum

Publications and helpful links

General Publications

• Kedhi E, Delewi R, Fabris E, De Luca G, Hermanides RS, van den Ent M, Buszman P, Zijlstra F, Song YB, Gwon HC, Hahn JY. Duration of dual antiplatelet therapy after myocardial infarction: Insights from a pooled database of the SMART-DATE and DAPT-STEMI trials. Atherosclerosis. 2020 Dec;315:55-61. doi: 10.1016/j.atherosclerosis.2020.11.003. Epub 2020 Nov 9.
• Postma W, Fabris E, Van der Ent M, Hermanides R, Buszman P, Von Birgelen C C, Cook S, Wedel H, De Luca G, Delewi R, Zijlstra F, Kedhi E. Resolute zotarolimus-eluting stent in ST-elevation myocardial infarction (resolute-STEMI): A prespecified prospective register from the DAPT-STEMI trial. Catheter Cardiovasc Interv. 2020 Mar 1;95(4):706-710. doi: 10.1002/ccd.28376. Epub 2019 Jul 3.
• Kedhi E, Fabris E, van der Ent M, Buszman P, von Birgelen C, Roolvink V, Zurakowski A, Schotborgh CE, Hoorntje JCA, Eek CH, Cook S, Togni M, Meuwissen M, van Royen N, van Vliet R, Wedel H, Delewi R, Zijlstra F. Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial. BMJ. 2018 Oct 2;363:k3793. doi: 10.1136/bmj.k3793.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: October 18, 2011
• First Submitted That Met QC Criteria: October 24, 2011
• First Posted (Estimate): October 25, 2011

Study Record Updates

• Last Update Posted (Actual): September 7, 2017
• Last Update Submitted That Met QC Criteria: September 6, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: STEMI; DAPT- Dual Antiplatelet Therapy
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Cardiovascular Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Prasugrel Hydrochloride
• Other Study ID Numbers: DAPT-STEMI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No