Clinical trial NCT01385319: Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates (ZEUS) Study
Official title: Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates (ZEUS) Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Coronary Artery Disease
Keywords: Bare metal stent
zotarolimus eluting stent
triple anti-thrombotic therapy
high bleeding riskduration of dual anti-platelet therapy
Lead sponsor: Università degli Studi di Ferrara
Sponsor class: OTHER
First posted: 2011-06-30
Enrollment: 1606
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

1. Patients with coronary artery disease lesions at low risk of in-stent restenosis;
2. Patients at high risk for bleeding or carrying impossibility to comply with dual anti-platelet treatment at long-term.
3. 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.

Eligibility criteria: 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

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

1. Clinical indication to treatment with oral anticoagulant, including use of warfarin or dabigatran or other oral anticoagulant agents
2. Recent (within previous 12 months) bleeding episode(s) which required medical attention
3. Previous bleeding episode(s) which required hospitalization if the bleeding diathesis has not been completely resolved (i.e. surgical removal of the bleeding source)
4. Age greater than 80
5. 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).
6. Known Anemia defined as repeatedly documented hemoglobin lower than 10 gr/dl which is not due to an acute and documented blood loss
7. Need for chronic treatment with steroids or NSAID

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

1. Allergy/intolerance to aspirin
2. Allergy/intolerance to clopidogrel AND ticlopidine
3. Planned surgery (other than skin) within 12 months of percutaneous coronary intervention (PCI).
4. patient with cancers (other than skin) and life expectancy \>1 year
5. 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:

     1. 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.
     2. Subjects who are unable to give informed consent and assurance for complete contact through 12 months.
     3. PCI with stenting in the previous 6 months

Primary outcomes:
measure: MACE
timeFrame: 12 months
Secondary outcomes:
measure: Death
timeFrame: 12 months
measure: myocardial infarction
timeFrame: 12 months
measure: TVR
timeFrame: 12 months
measure: stent thrombosis
timeFrame: 12 months
Other outcomes:
Locations:
city: Szeged
country: Hungary
facility: Albert Szent-Györgyi Clinical Center, University of Szeged
city: Arezzo
country: Italy
facility: Ospedale San Donato
state: AR
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
state: BG
city: Zingonia
country: Italy
facility: Policlinico San Marco
state: BG
city: Savigliano
country: Italy
facility: Ospedale di Savigliano
state: CN
city: Milano
country: Italy
facility: Istituto Clinico Sant'Ambrogio
state: MI
city: Modena
country: Italy
facility: Azienda Unita' Sanitaria Locale Di Modena - Ospedale Baggiovara
state: MO
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma
state: PR
city: Pavia
country: Italy
facility: Policlinico San Matteo
state: PV
city: Ravenna
country: Italy
facility: Ospedale di Ravenna
state: RA
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano di Torino, Ospedale Umberto I
state: TO
city: Torino
country: Italy
facility: Ospedale San Giovanni Bosco
state: TO
city: Ferrara
country: Italy
facility: University Hospital of Ferrara
city: Naples
country: Italy
facility: Clinica Mediterranea
city: Carnaxide
country: Portugal
facility: Hospital de Santa Cruz
city: Geneva
country: Switzerland
facility: University Hospital of Geneva
Study officials:
References:
citation: Ariotti S, Adamo M, Costa F, Patialiakas A, Briguori C, Thury A, Colangelo S, Campo G, Tebaldi M, Ungi I, Tondi S, Roffi M, Menozzi A, de Cesare N, Garbo R, Meliga E, Testa L, Gabriel HM, Ferlini M, Vranckx P, Valgimigli M; ZEUS Investigators. Is Bare-Metal Stent Implantation Still Justifiable in High Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention?: A Pre-Specified Analysis From the ZEUS Trial. JACC Cardiovasc Interv. 2016 Mar 14;9(5):426-36. doi: 10.1016/j.jcin.2015.11.015.
citation: Valgimigli M, Patialiakas A, Thury A, McFadden E, Colangelo S, Campo G, Tebaldi M, Ungi I, Tondi S, Roffi M, Menozzi A, de Cesare N, Garbo R, Meliga E, Testa L, Gabriel HM, Airoldi F, Ferlini M, Liistro F, Dellavalle A, Vranckx P, Briguori C; ZEUS Investigators. Zotarolimus-eluting versus bare-metal stents in uncertain drug-eluting stent candidates. J Am Coll Cardiol. 2015 Mar 3;65(8):805-815. doi: 10.1016/j.jacc.2014.11.053.
citation: Valgimigli M, Patialiakas A, Thury A, Colangelo S, Campo G, Tebaldi M, Ungi I, Tondi S, Roffi M, Menozzi A, de Cesare N, Garbo R, Meliga E, Testa L, Gabriel HM, Airoldi F, Ferlini M, Liistro F, Dellavalle A, Vranckx P, Briguori C. Randomized comparison of Zotarolimus-Eluting Endeavor Sprint versus bare-metal stent implantation in uncertain drug-eluting stent candidates: rationale, design, and characterization of the patient population for the Zotarolimus-eluting Endeavor Sprint stent in uncertain DES candidates study. Am Heart J. 2013 Nov;166(5):831-8. doi: 10.1016/j.ahj.2013.07.033. Epub 2013 Sep 26.