Prospective Registry to Asses the Long-term Safety and Performance of the Combo Stent (REMEDEE Reg)

Multicenter, Prospective, Clinical Outcomes After Deployment of the Abluminal Sirolimus Coated Bio-Engineered Stent (Combo Bio- Engineered Sirolimus Eluting Stent) Post Market Registry

Patients with stenosis in one or more coronary artery are often treated with a percutaneous coronary intervention (PCI). As part of the PCI treatment a stent is often placed to keep the vessel open over time.

The Combo-Stent is a novel stent for use during percutaneous angioplasty. In short, the Combo stent combines a drug eluting technique and an endothelial cell attracting layer. The drug coating is designed to prevent re-narrowing of the stent. The endothelial cell attracting layer is designed to ensure rapid coverage of the stent struts with vascular wall cells.

The REMEDEE REGISTRY evaluates the long-term safety and performance of the Combo stent in routine clinical practice. In total 1000 patients will be registered and followed for five years.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: Combo stent

Detailed Description

Registry Investigated Device:

The OrbusNeich Combo Bio-engineered Sirolimus Eluting Stent (Combo Stent) consists of a 316L stainless steel alloy abluminally coated with a biocompatible, biodegradable polymer containing sirolimus. Covalently attached to this matrix is a layer of murine, monoclonal, anti-human CD34 antibody. The antibody specifically targets CD34+ cells in circulation. Endothelial progenitor cells (EPCs) are CD34+. The stent is supplied premounted on a 0.014" guide wire compatible low profile rapid exchange balloon catheter delivery system. The Combo Stent is Conformitée Européenne (CE) marked.

Registry Objectives:

The REMEDEE REGISTRY evaluates the long term safety and performance of the Abluminal Sirolimus Coated Bio-Engineered Stent (Combo Bio-Engineered Sirolimus Eluting Stent) in routine clinical practice. The primary objective of the registry is to evaluate the one year incidence of target lesion failure in consecutive patients undergoing percutaneous coronary intervention with (attempted) Combo stent placement.

Registry Design:

The REMEDEE REGISTRY is an international, prospective, multicenter, cohort post market registry with five years follow-up to evaluate outcomes in patients undergoing percutaneous coronary intervention with (attempted) Combo stent placement. The registry population consists of consecutive patients in whom a treatment with a Combo stent in the setting of routine clinical care is attempted.

This registry involves the collection of baseline demographic, clinical, and angiographic data, as well as follow-up data in consecutive patients in whom the Combo stent is used to treat (a) coronary lesion(s) in the setting of routine clinical care. Patients are registered in up to 10 European high volume PCI centers. A follow-up is scheduled at 30 days, 180 days,1 year, 2 years, 3 years, 4 years and 5 years post procedure. Follow-up is obtained at a planned regular visit to the out-patient clinic, or by telephone contact with the patient.

Quality control:

All data will be entered on-site in an electronic case report (eCRF) form according to Good Clinical Practice guidelines.

All sites will monitored regularly during the time of the registry. The monitor plan involves a hundred percent procedural information and event monitoring. During data monitoring, all source data will be assessed for accuracy, completeness, and representativeness of registry data by comparing the data to external data sources. Data checks to compare data entered into the registry against predefined rules for range or consistency with other data fields in the registry are implemented in the (eCRF). A data dictionary that contains detailed descriptions of each variable used by the registry, including the source of the variable, coding information if used, and normal ranges if relevant is part of the database and eCRF design. Standard Operating Procedures to address registry operations and analysis activities, such as patient recruitment, data collection, data management, data analysis, reporting for adverse events, and change management are in place. A detailed statistical analysis plan describing the analytical principles and statistical techniques to be employed in order to address the primary and secondary objectives, as specified in the study protocol is available. Missing data is accounted for in the design of the eCRF template, and will be handled according to the statistical plan.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

Study Locations

• Latvia
  • Riga, Latvia, LV-1002
    • Pauls Stradins Clinical University Hospital
• Luxembourg
  • Luxembourg, Luxembourg
    • Centre Hospitalier de Luxembourg
• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • Academic Medical Center - University of Amsterdam
  • Blaricum, Netherlands
    • Ter Gooi Ziekenhuizen
  • Breda, Netherlands
    • Amphia Ziekenhuis
  • Nijmegen, Netherlands
    • Radboud UMC
  • Zwolle, Netherlands
    • Isala Klinieken
• Spain
  • Vigo, Spain
    • Meixoeiro Hospital
• United Kingdom
  • Craigavon, United Kingdom
    • Craigavon Cardiac Centre

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The registry population consists of consecutive patients in whom a treatment with a Combo stent in the setting of routine clinical care is attempted.

Description

Inclusion Criteria:

• Consecutive patients eligible for Combo stent placement by percutaneous coronary intervention are included in the REMEDEE REGISTRY

Exclusion Criteria:

• High probability of non-adherence to the follow-up requirements (due to social, psychological or medical reasons)
• Currently participating in another investigational drug or device study in which a routine angiographic follow-up is planned
• A life expectancy of <1 year
• Explicit refusal of participation in the registry

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Combo stent; Consecutive patients in whom a treatment with a Combo stent in the setting of routine clinical care is attempted are entered into the registry.

Device: Combo stent; Percutaneous coronary intervention of patients with an indication for stent treatment with the COMBO stent, a stent with an endothelial progenitor cell attracting coating and abluminal sirolimus matrix. All consecutive patients treated with, or attempted treatment with, a COMBO stent are followed by telephone contact for 5 years.; Other Names: Abluminal Sirolimus Coated Bio-Engineered Stent; Combo Bio-Engineered Sirolimus Eluting Stent; SirolimusECS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjudicated Target Lesion Failure	Adjudicated device-oriented composite target lesion failure (TLF) defined as a composite of cardiac death, non-fatal myocardial infarction (MI) not clearly attributable to a nontarget vessel, or target lesion revascularization (TLR) (percutaneous or by coronary artery bypass grafting).	1 year post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjudicated Target Lesion Failure	Adjudicated device-oriented composite target lesion failure (TLF) defined as a composite of cardiac death, non-fatal myocardial infarction (MI) not clearly attributable to a nontarget vessel, or target lesion revascularization (TLR) (percutaneous or by coronary artery bypass grafting).	30 days post-procedure
Adjudicated Target Lesion Failure	Adjudicated device-oriented composite target lesion failure (TLF) defined as a composite of cardiac death, non-fatal myocardial infarction (MI) not clearly attributable to a nontarget vessel, or target lesion revascularization (TLR) (percutaneous or by coronary artery bypass grafting).	180 days post procedure
Individual components of target lesion failure (TLF)	Individual components of target lesion failure (TLF): Cardiac death; Non-fatal MI not clearly attributable to a non-target vessel; Target lesion revascularization (TLR)	1 year post-procedure
Individual components of target lesion failure (TLF)	Individual components of TLF: Cardiac death; Non-fatal MI not clearly attributable to a non-target vessel; Target lesion revascularization (TLR)	30 days post-procedure
Individual components of target lesion failure (TLF)	Individual components of TLF: Cardiac death; Non-fatal MI not clearly attributable to a non-target vessel; Target lesion revascularization (TLR)	180 days post-procedure
Individual components of target lesion failure (TLF)	Individual components of TLF: Cardiac death; Non-fatal MI not clearly attributable to a non-target vessel; Target lesion revascularization (TLR)	1 year post-procedure
Adjudicated patient-oriented composite Major Adverse Cardiac Events (MACE)	Adjudicated patient-oriented composite MACE as a composite of: All death; Any myocardial infarction; Any revascularization	1 year post-procedure
Adjudicated patient-oriented composite Major Adverse Cardiac Events (MACE)	Adjudicated patient-oriented composite MACE as a composite of: All death; Any myocardial infarction; Any revascularization	30 days post-procedure
Adjudicated patient-oriented composite Major Adverse Cardiac Events (MACE)	Adjudicated patient-oriented composite MACE as a composite of: All death; Any myocardial infarction; Any revascularization	180 days post-procedure
Each of the individual components of Major Adverse Cardiac Events(MACE)	Each of the individual components of MACE: All death; Any myocardial infarction; Any revascularization	1 year post-procedure
Adjudicated stent thrombosis (definite/probable/possible)	Adjudicated stent thrombosis (definite/probable/possible) per Academic Research Consortium definitions	1 year post-procedure
Adjudicated stent thrombosis (definite/probable/possible)	Adjudicated stent thrombosis (definite/probable/possible) per Academic Research Consortium definitions	30 days post-procedure
Adjudicated stent thrombosis (definite/probable/possible)	Adjudicated stent thrombosis (definite/probable/possible) per Academic Research Consortium definitions	180 days post-procedure
Device success	Percentage of patients with a successful delivery and deployment of the Combo stent to the target lesion and a final diameter stenosis after stenting ≤20% by visual assessment in the presence of grade 3 TIMI flow, by visual estimation	Procedural
Procedure success	Successful stent placement and no periprocedural complications.	Procedural
Adjudicated Target Lesion Failure	Adjudicated device-oriented composite target lesion failure (TLF) defined as a composite of cardiac death, non-fatal myocardial infarction (MI) not clearly attributable to a nontarget vessel, or target lesion revascularization (TLR) (percutaneous or by coronary artery bypass grafting).	2 years post-procedure
Adjudicated Target Lesion Failure	Adjudicated device-oriented composite target lesion failure (TLF) defined as a composite of cardiac death, non-fatal myocardial infarction (MI) not clearly attributable to a nontarget vessel, or target lesion revascularization (TLR) (percutaneous or by coronary artery bypass grafting).	3 years post-procedure
Adjudicated Target Lesion Failure	Adjudicated device-oriented composite target lesion failure (TLF) defined as a composite of cardiac death, non-fatal myocardial infarction (MI) not clearly attributable to a nontarget vessel, or target lesion revascularization (TLR) (percutaneous or by coronary artery bypass grafting).	4 years post-procedure
Adjudicated Target Lesion Failure	Adjudicated device-oriented composite target lesion failure (TLF) defined as a composite of cardiac death, non-fatal myocardial infarction (MI) not clearly attributable to a nontarget vessel, or target lesion revascularization (TLR) (percutaneous or by coronary artery bypass grafting).	5 years post-procedure
Individual components of target lesion failure (TLF)	Individual components of target lesion failure (TLF): Cardiac death; Non-fatal MI not clearly attributable to a non-target vessel; Target lesion revascularization (TLR)	2 years post-procedure
Individual components of target lesion failure (TLF)	Individual components of target lesion failure (TLF): Cardiac death; Non-fatal MI not clearly attributable to a non-target vessel; Target lesion revascularization (TLR)	3 years post-procedure
Individual components of target lesion failure (TLF)	Individual components of target lesion failure (TLF): Cardiac death; Non-fatal MI not clearly attributable to a non-target vessel; Target lesion revascularization (TLR)	4 years post-procedure
Individual components of target lesion failure (TLF)	Individual components of target lesion failure (TLF): Cardiac death; Non-fatal MI not clearly attributable to a non-target vessel; Target lesion revascularization (TLR)	5 years post-procedure
Adjudicated patient-oriented composite Major Adverse Cardiac Events (MACE)	Adjudicated patient-oriented composite MACE as a composite of: All death; Any myocardial infarction; Any revascularization	2 years post-procedure
Adjudicated patient-oriented composite Major Adverse Cardiac Events (MACE)	Adjudicated patient-oriented composite MACE as a composite of: All death; Any myocardial infarction; Any revascularization	3 years post-procedure
Adjudicated patient-oriented composite Major Adverse Cardiac Events (MACE)	Adjudicated patient-oriented composite MACE as a composite of: All death; Any myocardial infarction; Any revascularization	4 years post-procedure
Adjudicated patient-oriented composite Major Adverse Cardiac Events (MACE)	Adjudicated patient-oriented composite MACE as a composite of: All death; Any myocardial infarction; Any revascularization	5 years post-procedure
Adjudicated stent thrombosis (definite/probable/possible)	Adjudicated stent thrombosis (definite/probable/possible) per Academic Research Consortium definitions	2 years post-procedure
Adjudicated stent thrombosis (definite/probable/possible)	Adjudicated stent thrombosis (definite/probable/possible) per Academic Research Consortium definitions	3 years post-procedure
Adjudicated stent thrombosis (definite/probable/possible)	Adjudicated stent thrombosis (definite/probable/possible) per Academic Research Consortium definitions	4 years post-procedure
Adjudicated stent thrombosis (definite/probable/possible)	Adjudicated stent thrombosis (definite/probable/possible) per Academic Research Consortium definitions	5 years post-procedure

Collaborators and Investigators

• Sponsor: Robbert J de Winter
• Investigators: Principal Investigator: Robbert J de Winter, MD, PhD, Academic Medical Centre - University of Amsterdam

Publications and helpful links

General Publications

• Granada JF, Inami S, Aboodi MS, Tellez A, Milewski K, Wallace-Bradley D, Parker S, Rowland S, Nakazawa G, Vorpahl M, Kolodgie FD, Kaluza GL, Leon MB, Virmani R. Development of a novel prohealing stent designed to deliver sirolimus from a biodegradable abluminal matrix. Circ Cardiovasc Interv. 2010 Jun 1;3(3):257-66. doi: 10.1161/CIRCINTERVENTIONS.109.919936. Epub 2010 May 4.
• Nakazawa G, Granada JF, Alviar CL, Tellez A, Kaluza GL, Guilhermier MY, Parker S, Rowland SM, Kolodgie FD, Leon MB, Virmani R. Anti-CD34 antibodies immobilized on the surface of sirolimus-eluting stents enhance stent endothelialization. JACC Cardiovasc Interv. 2010 Jan;3(1):68-75. doi: 10.1016/j.jcin.2009.09.015.
• Chandrasekhar J, Kok MM, Kalkman DN, Aquino MB, Zocca P, Woudstra P, Beijk MA, Kerkmeijer LS, Sartori S, Baber U, Tijssen JG, Koch KT, Dangas GD, Colombo A, Pocock S, von Birgelen C, Mehran R, de Winter RJ; COMBO Collaborators and BIO-RESORT Investigators. 1-Year Clinical Outcomes of All Comers Treated With 2 Bioresorbable Polymer-Coated Sirolimus-Eluting Stents: Propensity Score-Matched Comparison of the COMBO and Ultrathin-Strut Orsiro Stents. JACC Cardiovasc Interv. 2020 Apr 13;13(7):820-830. doi: 10.1016/j.jcin.2019.11.023.
• Chandrasekhar J, Kerkmeijer LS, Kalkman DN, Sartori S, Aquino MB, Woudstra P, Beijk MA, Tijssen JG, Koch KT, Hajek P, Atzev B, Hudec M, Ong TK, Mates M, Borisov B, Warda HM, den Heijer P, Wojcik J, Iniguez A, Coufal Z, Khashaba A, Munawar M, Gerber RT, Yan BP, Lee M, Baber U, Dangas GD, Colombo A, de Winter RJ, Mehran R; MASCOT and REMEDEE investigators (full list of collaborators shown in the Appendix). Sex differences in 1-year clinical outcomes after percutaneous coronary intervention with COMBO stents: From the COMBO collaboration. Catheter Cardiovasc Interv. 2021 Apr 1;97(5):797-804. doi: 10.1002/ccd.28853. Epub 2020 Mar 21.
• Kalkman DN, Kerkmeijer LS, Woudstra P, Menown IBA, Suryapranata H, den Heijer P, Iniguez A, van 't Hof AWJ, Erglis A, Arkenbout KE, Muller P, Koch KT, Tijssen JG, Beijk MAM, de Winter RJ. Three-year clinical outcomes after dual-therapy COMBO stent placement: Insights from the REMEDEE registry. Catheter Cardiovasc Interv. 2019 Sep 1;94(3):342-347. doi: 10.1002/ccd.28047. Epub 2018 Dec 18.
• Kalkman DN, Woudstra P, Menown IBA, den Heijer P, Van't Hof AW, Erglis A, Suryapranata H, Arkenbout KE, Iniguez A, Muller P, Tijssen JG, Beijk MAM, de Winter RJ. Two-year clinical outcomes of patients treated with the dual-therapy stent in a 1000 patient all-comers registry. Open Heart. 2017 Jul 11;4(2):e000634. doi: 10.1136/openhrt-2017-000634. eCollection 2017.
• Woudstra P, Kalkman DN, den Heijer P, Menown IB, Erglis A, Suryapranata H, Arkenbout KE, Iniguez A, van 't Hof AW, Muller P, Tijssen JG, de Winter RJ. 1-Year Results of the REMEDEE Registry: Clinical Outcomes After Deployment of the Abluminal Sirolimus-Coated Bioengineered (Combo) Stent in a Multicenter, Prospective All-Comers Registry. JACC Cardiovasc Interv. 2016 Jun 13;9(11):1127-34. doi: 10.1016/j.jcin.2016.02.052. Epub 2016 May 18.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): March 1, 2015
• Study Completion (ANTICIPATED): March 1, 2019

Study Registration Dates

• First Submitted: June 6, 2013
• First Submitted That Met QC Criteria: June 6, 2013
• First Posted (ESTIMATE): June 10, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 30, 2015
• Last Update Submitted That Met QC Criteria: December 29, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: PCI; Stents; Stent; Percutaneous Coronary Intervention; Multi center; Drug eluting stent; Registry; Sirolimus; Drug eluting stents; Registries; Endothelial progenitor cell; Drug eluting; Endothelial progenitor cell capturing; Sirolimus eluting; Multi centre
• 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-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: W12_186; Version 2.0 (Sponsor)