Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates (ZEUS) Study

Sponsor

Marco Valgimigli (Other)

Overall Status

Unknown status

CT.gov ID

NCT01385319

Collaborator

(none)

1,606

Enrollment

Locations

Arms

Duration (Months)

100.4

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To prospectively evaluate in a multicenter open label trial whether the use of zotarolimus-eluting ENDEAVOR Stent implantation in patients at low restenosis or at high bleeding or thrombotic risk will decrease the incidence of 12-month major adverse cardiac events (MACE) including overall death, any myocardial infarction (MI) or any target vessel revascularization (TVR).

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Device: Bare metal stent implantation Device: zotarolimus eluting stent	Phase 3

Detailed Description

The aim of this study is to conduct a multicenter, international, randomized trial to test whether the Endeavor stent is superior to BMS in terms of efficacy and safety in

Patients with coronary artery disease lesions at low risk of in-stent restenosis;
Patients at high risk for bleeding or carrying impossibility to comply with dual anti-platelet treatment at long-term.
Patients at high thrombosis risk due to systemic disorders or planned non-cardiac surgery within 12 months

As the use of DES in these two patient/lesion subsets is debated due to lack of evidence, patients fulfilling at least one of these three medical conditions qualify for bare metal stent implantation and physicians may believe DES to be even contra-indicated in such cases. The current protocol has been developed on purpose to address the value of the Endeavor Sprint stent, which differs in many aspects from other FDA approved DES, including fast and complete degree of strut coverage after implantation and quick release of active drug after deployment (~15 days) which may help decreasing the need for prolonged dual antiplatelet treatment down to 1 month as it is currently recommended for bare metal stent implantation.

Study Design

Study Type:

Interventional

Actual Enrollment :

1606 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates (ZEUS) Study

Study Start Date :

Jun 1, 2011

Actual Primary Completion Date :

Sep 1, 2012

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: bare metal stent	Device: Bare metal stent implantation After BMS implantation the duration of dual anti-platelet therapy is a function of the clinical presentation and the bleeding risk a given patient as follows: Clopidogrel will be given for 1 month after PCI if indication to the procedure is stable coronary artery disease or for at least 6 month if indication to the procedure is ACS, including STEMI or NSTEACS. At discretion of the treating physician, prasugrel or ticagrelor may replace clopidogrel in ACS patients. Patients recruited in the study due to high bleeding risk will receive clopidogrel for at least 30 days. Patients recruited in the study due to high thrombosis risk will receive clopidogrel monotherapy life long or DAPT for at least 1 month.
Experimental: Endeavor sprint stent	Device: zotarolimus eluting stent After ZES implantation the duration of dual anti-platelet therapy is a function of the clinical presentation and the bleeding risk a given patient (i.e. identical to criteria set out for BMS patients) as follows: Clopidogrel will be given for 1 month after PCI if indication to the procedure is stable coronary artery disease or for at least 6 month if indication to the procedure is ACS, including STEMI or NSTEACS. At discretion of the treating physician, prasugrel or ticagrelor may replace clopidogrel in ACS patients. Patients recruited in the study due to high bleeding risk will receive clopidogrel for at least 30 days. Patients recruited in the study due to high thrombosis risk will receive clopidogrel monotherapy life long or DAPT for at least 1 month.

Arm

Intervention/Treatment

Active Comparator: bare metal stent

Device: Bare metal stent implantation

After BMS implantation the duration of dual anti-platelet therapy is a function of the clinical presentation and the bleeding risk a given patient as follows: Clopidogrel will be given for 1 month after PCI if indication to the procedure is stable coronary artery disease or for at least 6 month if indication to the procedure is ACS, including STEMI or NSTEACS. At discretion of the treating physician, prasugrel or ticagrelor may replace clopidogrel in ACS patients. Patients recruited in the study due to high bleeding risk will receive clopidogrel for at least 30 days. Patients recruited in the study due to high thrombosis risk will receive clopidogrel monotherapy life long or DAPT for at least 1 month.

Experimental: Endeavor sprint stent

Device: zotarolimus eluting stent

After ZES implantation the duration of dual anti-platelet therapy is a function of the clinical presentation and the bleeding risk a given patient (i.e. identical to criteria set out for BMS patients) as follows: Clopidogrel will be given for 1 month after PCI if indication to the procedure is stable coronary artery disease or for at least 6 month if indication to the procedure is ACS, including STEMI or NSTEACS. At discretion of the treating physician, prasugrel or ticagrelor may replace clopidogrel in ACS patients. Patients recruited in the study due to high bleeding risk will receive clopidogrel for at least 30 days. Patients recruited in the study due to high thrombosis risk will receive clopidogrel monotherapy life long or DAPT for at least 1 month.

Outcome Measures

Primary Outcome Measures

MACE [12 months]
Major adverse cardiovascular events including death for any cause, non-fatal myocardial infarction or target vessel revascularisation

Secondary Outcome Measures

Death [12 months]
myocardial infarction [12 months]
TVR [12 months]
target vessel revascularisation
stent thrombosis [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

A) low restenosis risk based on angiographic findings defined as follows:

----patients will be considered at low restenosis risk if no planned stent lower than 3.0 mm is intended to be implanted in lesions expect left main or vein graft

high bleeding risk and/or presence of relative-absolute contraindication to dual anti-platelet treatment beyond 30 days defined as follows:

Clinical indication to treatment with oral anticoagulant, including use of warfarin or dabigatran or other oral anticoagulant agents
Recent (within previous 12 months) bleeding episode(s) which required medical attention
Previous bleeding episode(s) which required hospitalization if the bleeding diathesis has not been completely resolved (i.e. surgical removal of the bleeding source)
Age greater than 80
Systemic conditions associated to increased bleeding risk (e.g. hematological disorders or any known coagulopathy determining bleeding diathesis, including history of or current thrombocytopenia defined as platelet count <100,000/mm3 (<100 x 109/L).
Known Anemia defined as repeatedly documented hemoglobin lower than 10 gr/dl which is not due to an acute and documented blood loss
Need for chronic treatment with steroids or NSAID

Patients at high thrombosis risk based on the presence of at least one of the following criteria:

Allergy/intolerance to aspirin
Allergy/intolerance to clopidogrel AND ticlopidine
Planned surgery (other than skin) within 12 months of percutaneous coronary intervention (PCI).
patient with cancers (other than skin) and life expectancy >1 year
Patients with systemic conditions associated with thrombosis diathesis (e.g., hematologic disorders and any known systemic conditions determining a pro-thrombotic state including immunological disorders)

Exclusion Criteria:

Any of the following:

Women who are pregnant. Women of childbearing potential must have a negative pregnancy test (urine or serum HCG) within 7 days prior to randomization; as close to randomization as possible, within 24 hours preferred.
Subjects who are unable to give informed consent and assurance for complete contact through 12 months.
PCI with stenting in the previous 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Albert Szent-Györgyi Clinical Center, University of Szeged	Szeged		Hungary
2	Ospedale San Donato	Arezzo	AR	Italy	52100
3	Ospedali Riuniti di Bergamo	Bergamo	BG	Italy	24128
4	Policlinico San Marco	Zingonia	BG	Italy	24040
5	Ospedale di Savigliano	Savigliano	CN	Italy	12038
6	Istituto Clinico Sant'Ambrogio	Milano	MI	Italy	20149
7	Azienda Unita' Sanitaria Locale Di Modena - Ospedale Baggiovara	Modena	MO	Italy	41100
8	Azienda Ospedaliero-Universitaria di Parma	Parma	PR	Italy	43126
9	Policlinico San Matteo	Pavia	PV	Italy	27100
10	Ospedale di Ravenna	Ravenna	RA	Italy	48121
11	Azienda Ospedaliera Ordine Mauriziano di Torino, Ospedale Umberto I	Torino	TO	Italy	10128
12	Ospedale San Giovanni Bosco	Torino	TO	Italy	10154
13	University Hospital of Ferrara	Ferrara		Italy	44100
14	Clinica Mediterranea	Naples		Italy	80122
15	Hospital de Santa Cruz	Carnaxide		Portugal
16	University Hospital of Geneva	Geneva		Switzerland