Randomized Study Comparing Endeavor With Cypher Stents (PROTECT) (PROTECT)

PROTECT Trial: Patient Related OuTcomes With Endeavor Versus Cypher Stenting Trial

The PROTECT TRIAL is a randomized stent trial with 8800 patients in approximately 200 hospitals, which is designed to evaluate whether the Endeavor stent PROTECTS against late stent thrombosis resulting in less deaths and myocardial infarctions.

Study Stents:

Medtronic Endeavor® Zotarolimus Eluting Coronary Stent System or next generation model Cordis Cypher® Sirolimus-eluting Coronary Stent, Cordis Cypher Select® Sirolimus-eluting Coronary Stent or next generation model

Primary Objective: To compare overall stent thrombosis rate of the Endeavor® Zotarolimus Eluting Coronary Stent System versus the Cypher® Sirolimus-eluting Coronary Stent in a patient population requiring stent implantation

Secondary Objective: To compare the composite endpoint of total death or cardiac death combined with the number of patients with all non-fatal myocardial infarctions as well as the number of patients with large non-fatal myocardial infarctions for Endeavor® Zotarolimus Eluting Coronary Stent System versus the Cypher® Sirolimus-eluting Coronary Stent in a patient population requiring stent implantation.

To assess the safety and efficacy in patient subgroups with specific demographics, clinical indications and/or vessel- or lesion characteristics.

Study Overview

• Status: Completed
• Conditions: Ischemic Heart Disease
• Intervention / Treatment: Device: Stent

• Study Type: Interventional
• Enrollment (Actual): 8709
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • 196 enrolling sites Worldwide

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. Patient is > 18 years of age (or minimum age as required by local regulations).
2. The patient has consented to participate and has authorized the collection and release of his medical information by signing the "Patient Informed Consent Form".
3. All lesions requiring interventions (target lesions - one to a maximum of four) in one or more native coronary arteries are amendable for implantation of one or more Endeavor® Zotarolimus Eluting Coronary Stent System or Cypher® Sirolimus-eluting Coronary Stent*.
4. Patient indication, lesion length and vessel diameter of the target lesion(s) are according to the 'Indications for Use' as mentioned in the 'Instructions for Use' that comes with every Endeavor® Zotarolimus Eluting Coronary Stent System and Cypher® Sirolimus-eluting Coronary Stent. Patients should qualify for both systems before randomization*.
5. The patient is willing and able to cooperate with study procedures and required follow up visits.

Exclusion Criteria:

1. Women with known pregnancy or who are lactating.
2. Planned elective surgery necessitating discontinuation of clopidogrel within the regular planned period of clopidogrel administration.
3. Patients expected not to be compliant with the anti-platelet and/or anticoagulation therapy regimen.
4. Previous brachy-therapy.
5. Previous implantation of a drug eluting stent.
6. Previous implantation of a bare metal stent in the preceding year.
7. Simultaneous or planned intervention other non cardiac vessels including but not limited to renal artery or carotid artery.
8. Current medical condition with a life expectancy of less than 3 years.
9. Manifest acute severe heart failure (Killip class III-IV).
10. The patient is currently, and during the first 3 years of the PROTECT trial, participating in another investigational device or drug study that clinically interferes with the PROTECT-study endpoints; or requires coronary angiography or other coronary artery imaging procedures. The patient may only be enrolled in the PROTECT-study once.
11. Patients with medical conditions that preclude the follow-up as defined in the protocol or that otherwise limits participation in this study.
12. Patients on warfarin or similar anti-coagulant therapy.
13. Patients with hypersensitivity or allergies to one of the drugs or components indicated in the Instructions for Use of either stents.
14. Patients who are judged to have a lesion that prevents complete inflation of an angioplasty balloon.
15. Patients in whom anti-platelet and/or anticoagulation therapy is contraindicated.
16. Transplant patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Medtronic Endeavor® Zotarolimus Eluting Coronary Stent System	Device: Stent; Stent implantation; Other Names: Cordis Cypher® Sirolimus-eluting Coronary Stent
Active Comparator: 2; Cordis Cypher® Sirolimus-eluting Coronary Stent	Device: Stent; Stent implantation; Other Names: Cordis Cypher® Sirolimus-eluting Coronary Stent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Compare Overall Definite or Probable Stent Thrombosis Rate of the Endeavor® Zotarolimus Eluting Coronary Stent System Versus the Cypher® Sirolimus-eluting Coronary Stent in a Patient Population Requiring Stent Implantation	Definite or probable stent thrombosis rate.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composites of (Cardiac) Death and (Large) Non-fatal Myocardial Infarctions	Total death and large non-fatal myocardial infarctions Total death and non-fatal myocardial infarctions Cardiac death and large non-fatal MI Cardiac death and non-fatal myocardial infarctions	3 years

Collaborators and Investigators

• Sponsor: Medtronic Vascular
• Collaborators: Medtronic Bakken Research Center
• Investigators: Principal Investigator: Edoardo Camenzind, MD, University of Geneva, Switzerland; Principal Investigator: Laura Mauri, MD, Brigham and Women's Hospital, US; Principal Investigator: William O'Neill, MD, University of Miami Miller School of Medicine, US; Principal Investigator: Prof. Patrick W. Serruys, MD, PhD, Erasmus Medical Center; Principal Investigator: Prof. Philippe Gabriel Steg, MD, PhD, Département de Cardiologie, Hôpital Bichat-Claude Bernard, Assistance Publique - Hôpitaux de Paris, France; Principal Investigator: William Wijns, MD, PhD, O.L.V. Hospital, Aalst, Belgium

Publications and helpful links

General Publications

• Camenzind E, Wijns W, Mauri L, Boersma E, Parikh K, Kurowski V, Gao R, Bode C, Greenwood JP, Gershlick A, O'Neill W, Serruys PW, Jorissen B, Steg PG; PROTECT Steering Committee and Investigators. Rationale and design of the Patient Related OuTcomes with Endeavor versus Cypher stenting Trial (PROTECT): randomized controlled trial comparing the incidence of stent thrombosis and clinical events after sirolimus or zotarolimus drug-eluting stent implantation. Am Heart J. 2009 Dec;158(6):902-909.e5. doi: 10.1016/j.ahj.2009.10.002.
• Camenzind E, Wijns W, Mauri L, Kurowski V, Parikh K, Gao R, Bode C, Greenwood JP, Boersma E, Vranckx P, McFadden E, Serruys PW, O'Neil WW, Jorissen B, Van Leeuwen F, Steg PG; PROTECT Steering Committee and Investigators. Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial. Lancet. 2012 Oct 20;380(9851):1396-405. doi: 10.1016/S0140-6736(12)61336-1. Epub 2012 Aug 27.
• Roguin A, Camenzind E, Kerner A, Beyar R, Boersma E, Mauri L, Steg PG, Wijns W. Long-Term Outcomes of Stenting the Proximal Left Anterior Descending Artery in the PROTECT Trial. JACC Cardiovasc Interv. 2017 Mar 27;10(6):548-556. doi: 10.1016/j.jcin.2016.12.028.
• Secemsky EA, Matteau A, Yeh RW, Steg PG, Camenzind E, Wijns W, McFadden E, Mauri L; PROTECT Trial Investigators. Comparison of Short- and Long-Term Cardiac Mortality in Early Versus Late Stent Thrombosis (from Pooled PROTECT Trials). Am J Cardiol. 2015 Jun 15;115(12):1678-84. doi: 10.1016/j.amjcard.2015.03.010. Epub 2015 Mar 23.
• Wijns W, Steg PG, Mauri L, Kurowski V, Parikh K, Gao R, Bode C, Greenwood JP, Lipsic E, Alamgir F, Rademaker-Havinga T, Boersma E, Radke P, van Leeuwen F, Camenzind E; PROTECT Steering Committee and Investigators. Endeavour zotarolimus-eluting stent reduces stent thrombosis and improves clinical outcomes compared with cypher sirolimus-eluting stent: 4-year results of the PROTECT randomized trial. Eur Heart J. 2014 Oct 21;35(40):2812-20. doi: 10.1093/eurheartj/ehu318. Epub 2014 Aug 8.
• Camenzind E, Boersma E, Wijns W, Mauri L, Rademaker-Havinga T, Ordoubadi FF, Suttorp MJ, Al Kurdi M, Steg PG; PROTECT Steering Committee and Investigators. Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type. Eur Heart J. 2014 Aug 1;35(29):1932-48. doi: 10.1093/eurheartj/ehu084. Epub 2014 Mar 13.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: May 21, 2007
• First Submitted That Met QC Criteria: May 21, 2007
• First Posted (Estimate): May 22, 2007

Study Record Updates

• Last Update Posted (Estimate): November 10, 2014
• Last Update Submitted That Met QC Criteria: November 3, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Interventional Cardiology; Drug Eluting Stents
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: Version 1.0 - 12 April 2007