Comparison of the Everolimus Eluting With the Biolimus A9 Eluting Stent (COMPARE-II)

Comparison of the Everolimus Eluting (XIENCE-V®, XIENCE-Prime® or PROMUS® Stent) With the Biolimus A9 Eluting NOBORI® Stent in All-comers: a Randomized Open Label Study

This is a prospective, randomized, multi center study. Approximately 2700 patients will be entered in the study and will be randomized on a 2:1 basis. Patients who meet the eligibility criteria will be randomized to the everolimus eluting XIENCE-V®, XIENCE-Prime® or PROMUS® stent versus the Biolimus A9 eluting NOBORI® stent. Patients will be followed for 5 years.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: the everolimus eluting ® stent; Device: the Biolimus A9 eluting NOBORI® stent

Detailed Description

The main objective of the study is a head to head comparison of the everolimus eluting XIENCE-V ®, XIENCE-Prime® or PROMUS ® stent with the biolimus A9 eluting NOBORI® stent in order to observe whether there is a difference in clinical outcome between both stents in a real world / all-comer situation.

Clinical outcome of both stents will be assessed by the composite end point of: cardiac death, non fatal myocardial infarction and target vessel revascularization.

Endpoints

The primary end point of the study is the composite of safety (cardiac death, non fatal myocardial infarction) and efficacy (target vessel revascularization) at 12 months.

The secondary end points of the study are:

A) The combined endpoint of cardiac death, non fatal myocardial infarction, ischemic driven target lesion revascularization (TLR) rate at 12 months follow-up.

B) Incidence of Cardiac Death and Post-Procedural (>48h) MI rate at 12 months, 3 and 5 years C) Target lesion revascularization at 12 months, 3 and 5 years D) The combined endpoint of cardiac death, non fatal myocardial infarction, target vessel revascularization (TVR) rate at 3 and 5 years follow-up.

E) The combined endpoint of cardiac death, non fatal myocardial infarction and target vessel revascularization at 12 months, 3 and 5 years in STEMI patients, small vessels (< 2.75 mm RVD), long lesions (> 20 mm), female patients, DM patients and octogenarians. F) Procedural performance at the index procedures, measured by the ability to cross the lesions with the designated DES stent.

G) Incidence of definite and probable stent thrombosis at 12 months, 3 and 5 years time.

H) Incidence of definite, probable and possible stent thrombosis at 12 months, 3 and5 years time.

Overview of the study

This is a prospective, randomized, multi center study. Approximately 2700 patients will be entered in the study and will be randomized on a 2:1 basis. Patients who meet the eligibility criteria will be randomized to the everolimus eluting XIENCE-V®, XIENCE-Prime® or PROMUS® stent versus the Biolimus A9 eluting NOBORI® stent. Patients will be followed for 5 years.

The study population will consist of approximately 2700 patients (1 year enrollment of consecutive all-comers referred for percutaneous coronary intervention (PCI) with coronary artery or by-pass grafts lesions). Patients must meet all eligibility criteria for inclusion into the study.

Randomization will be performed by using a closed envelope with code N for the NOBORI stent and code E for the Everolimus eluting stent. Duration of the study The enrollment phase will start January 2009 and will stop December 2010. The followup phase will last till December 2015.

• Study Type: Interventional
• Enrollment (Anticipated): 2700
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece
    • Onassis Cardiac Surgery Centre
• Netherlands
  • Amsterdam, Netherlands
    • Onze Lieve Vrouwe Gasthuis
  • Breda, Netherlands
    • Amphia Ziekenhuis
  • Leeuwarden, Netherlands
    • Medisch Centrum Leeuwarden
  • Rotterdam, Netherlands
    • Maasstad Hospital
• Spain
  • Barcelona, Spain
    • Hospital Del Mar
  • Coruña, Spain
    • Complejo Hospitalario Universitario Juan Canalejo
  • Murcia, Spain
    • Hospital Universitario Virgen Arrixaca
  • Santiago de Compostella, Spain
    • Hospital Clinico universitario de Santiago de Compostella
• Switzerland
  • Aarau, Switzerland
    • Kantonsspital Aarau
  • Fribourg, Switzerland
    • Hôpital Cantonal de Fribourg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The patient is at least 18 years old and has a life expectancy of 5 years.
2. Patient undergoes a PCI procedure for indications according to the Dutch and European guidelines
3. Patient is willing to comply with the extended follow-up period of 2 to 5 years(for secondary endpoint only)
4. Reference lumen diameter of the treated vessels between 2.0 - 4.0 mm.
5. Informed consent

Exclusion Criteria:

1. Expected non-adherence to dual antiplatelet therapy for 1 year (e.g: known allergy to ASA or thienopyridines like clopidogrel)
2. Expected major surgery within 30 days (these patients will receive bare metal stents)
3. Cardiogenic shock (Kilip class 4)
4. Previous PCI procedures with implantation of drug eluting stents within 1 year.
5. Expected loss for follow up
6. Enrollment in an investigative stent study with different stents
7. Inability to implant Nobori or Xience-V / Promus stent(s)

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: the everolimus eluting ® stent; the everolimus eluting XIENCE-V®, XIENCE-Prime® or PROMUS® stent	Device: the everolimus eluting ® stent; stenting in coronary artery disease using the XIENCE-V®, XIENCE-Prime® or PROMUS® stent
Active Comparator: Biolimus A9 stent; the Biolimus A9 eluting NOBORI® stent	Device: the Biolimus A9 eluting NOBORI® stent; stenting in coronary artery disease using the Biolimus A9 eluting NOBORI® stent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse coronary events	composite of cardiac death, non fatal myocardial infarction and target vessel revascularization	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse coronary events	The combined endpoint of cardiac death, non fatal myocardial infarction, ischemic driven target lesion revascularization (TLR) rate at 12 months follow-up.	12 months
Safety of stenting with drug eluting stents	Incidence of Cardiac Death and Post-Procedural (>48h) MI rate at 12 months, 3 and 5 years	5 years
Target lesion revascularization	Target lesion revascularization at 12 months, 3 and 5 years	5 years
Late major adverse coronary events	The combined endpoint of cardiac death, non fatal myocardial infarction, target vessel revascularization (TVR) rate at 3 and 5 years follow-up.	5 years
Major adverse coronary events in subgroups	The combined endpoint of cardiac death, non fatal myocardial infarction and target vessel revascularization at 12 months, 3 and 5 years in STEMI patients, small vessels (< 2.75 mm RVD), long lesions (> 20 mm), female patients, DM patients and octogenarians	5 years
Procedural performance	Procedural performance at the index procedures, measured by the ability to cross the lesions with the designated DES stent.	1 year
Stent Thrombosis	Incidence of definite and probable stent thrombosis at 12 months, 3 and 5 years time. Incidence of definite, probable or possible stent thrombosis at 12 months, 3 and 5 years time	5 years

Collaborators and Investigators

• Sponsor: Maasstad Hospital
• Investigators: Principal Investigator: Pieter C Smits, MD, PHD, Maasstad Ziekenhuis; Study Chair: A Serra, MD, Hospital Del Mar; Study Chair: A J van Boven, MD, PHD, Medisch Centrum Leeuwarden; Study Chair: J J Goy, MD, Hôpital Cantonal de Fribourg; Study Chair: V Voudris, MD, Onassis Heart Centre, Athens

Publications and helpful links

General Publications

• Vlachojannis GJ, Smits PC, Hofma SH, Togni M, Vazquez N, Valdes M, Voudris V, Puricel S, Slagboom T, Goy JJ, den Heijer P, van der Ent M. Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer everolimus-eluting stents in patients with coronary artery disease: three-year follow-up of the COMPARE II (Abluminal biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent) trial. EuroIntervention. 2015 Jul;11(3):272-9. doi: 10.4244/EIJV11I3A53.
• Smits PC, Hofma S, Togni M, Vazquez N, Valdes M, Voudris V, Slagboom T, Goy JJ, Vuillomenet A, Serra A, Nouche RT, den Heijer P, van der Ent M. Abluminal biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent (COMPARE II): a randomised, controlled, non-inferiority trial. Lancet. 2013 Feb 23;381(9867):651-60. doi: 10.1016/S0140-6736(12)61852-2. Epub 2013 Jan 30.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): May 1, 2012
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: October 28, 2010
• First Submitted That Met QC Criteria: November 2, 2010
• First Posted (Estimate): November 3, 2010

Study Record Updates

• Last Update Posted (Estimate): January 30, 2014
• Last Update Submitted That Met QC Criteria: January 29, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus; Umirolimus
• Other Study ID Numbers: NL25754.101.08