Clinical trial NCT01459627: Randomized, Open Label Trial of 6 Months Versus 12 Months DAPT After Drug-Eluting Stent in STEMI
Official title: Prospective, Randomized, Open Label Trial of 6 Months vs. 12 Months Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myocardial Infarction
Cardiovascular Disease
Keywords: DAPT- Dual Antiplatelet Therapy
STEMI
Lead sponsor: Maasstad Hospital
Sponsor class: OTHER
Collaborators: name: Medtronic
First posted: 2011-10-25
Enrollment: 1100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Net MACCE
timeFrame: 18 months
Secondary outcomes:
measure: All cause mortality, MI, Stroke, ST and bleeding
timeFrame: 2 days
measure: All cause mortality, MACCE, TIMI
timeFrame: 9 months
measure: ST definite/probable
timeFrame: 9 months
measure: all cause mortality
timeFrame: 9 months
measure: Cardiac mortality
timeFrame: 9 months
measure: MI
timeFrame: 9 months
measure: Target vessel MI
timeFrame: 9 months
measure: Bleeding
timeFrame: 9 months
measure: stroke
timeFrame: 9 months
measure: Target vessel revascularization
timeFrame: 9 months
measure: Target lesion revascularization
timeFrame: 9 months
measure: Target vessel failure
timeFrame: 9 months
measure: Target lesion failure
timeFrame: 9 months
measure: net MACCE
timeFrame: 30days
measure: All cause mortality, MI, Stroke, ST and bleeding
timeFrame: 30 days
measure: net MACCE
timeFrame: 6 months
measure: All cause mortality, MACCE, TIMI
timeFrame: 18 months
measure: ST definite/probable
timeFrame: 18 months
measure: All cause mortality
timeFrame: 18 months
measure: Cardiac mortality
timeFrame: 18 months
measure: MI
timeFrame: 18 months
measure: Target vessel MI
timeFrame: 18 months
measure: Bleeding
timeFrame: 18 months
measure: Stroke
timeFrame: 18 months
measure: Target vessel revascularization
timeFrame: 18 months
measure: Target lesion revascularization
timeFrame: 18 months
measure: Target vessel failure
timeFrame: 18 months
measure: Target lesion failure
timeFrame: 18 months
measure: ST following ARC
timeFrame: 2 days
measure: ST following ARC
timeFrame: 30 days
measure: All cause mortality
timeFrame: 2 days
measure: All cause mortality
timeFrame: 30 days
measure: Cardiac mortality
timeFrame: 2 days
measure: Cardiac Mortality
timeFrame: 30 days
measure: All MI
timeFrame: 2 days
measure: All MI
timeFrame: 30 days
measure: Target vessel MI
timeFrame: 2 days
measure: Target vessel MI
timeFrame: 30 days
measure: Bleeding BARC
timeFrame: 2 days
measure: Bleeding (BARC)
timeFrame: 30 days
measure: Stroke
timeFrame: 2 days
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU medisch Centrum
city: Breda
country: Netherlands
facility: Amphia ziekenhuis
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Heerlen
country: Netherlands
facility: Atrium MC Parkstad
city: Rotterdam
country: Netherlands
facility: Maasstadhospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: The Hague
country: Netherlands
facility: Haga Hospital
city: Zwolle
country: Netherlands
facility: Isala Clinics
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Bielsko-Biala
country: Poland
facility: Amerykańskie Kliniki Serca
city: Chrzanów
country: Poland
facility: Małopolskie Centrum Sercowo-Naczyniowe PAKS
city: Dąbrowa Górnicza
country: Poland
facility: Polsko-Amerykańskie Kliniki Serca
city: Kedzierzyn Kozle
country: Poland
facility: Polsko_Amerykanskei Kliniki Serca
city: Krakow
country: Poland
facility: University Hospital in Krakow
city: Nysa
country: Poland
facility: Polsko_Amerykanskei Kliniki Serca
city: Fribourg
country: Switzerland
facility: Hôpital Cantonal Fribourg
Study officials:
affiliation: Isala
name: Elvin Kedhi, MD PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maasstadhospital / MCR B.V.
name: Martin van der Ent, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medisch Spectrum Twente
name: Clemens von Birgelen, MD PhD
role: STUDY_CHAIR
affiliation: Erasmus Medisch Centrum
name: Felix Zijlstra, MD PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.