COMBO-Stent in Patients on Chronic Anticoagulant Therapy (COSTA) COSTA-Bleed and COSTA-Outcome Trials (COSTA)

Prospective, Multi-centre, Randomized, Parallel Comparison to Evaluate the Safety and Efficacy of the Abluminal Sirolimus Coated Bio-engineered Stent (COMBO Stent) in Association With Short-term Single Antiplatelet Therapy in Patients With Coronary Artery Disease With an Indication for Chronic Oral Anticoagulant Therapy as Compared to a Guidelines-based Strategy

Prospective, multi-centre, randomized, open-label, parallel comparisons to evaluate

• the incidence of bleedings (COSTA-Bleed) and
• the incidence of ischemic and bleeding events (COSTA-Outcome) following a therapy with the abluminal sirolimus coated bio-engineered stent (COMBO stent) in association with short-term single antiplatelet therapy as compared to a guidelines-based strategy in patients with coronary artery disease with an indication for chronic oral anticoagulant therapy.

Study Overview

• Status: Withdrawn
• Conditions: Coronary Disease; Stable Angina; Unstable Angina; STEMI; NSTEMI
• Intervention / Treatment: Device: COMBO-Stent; Drug: Clopidogrel, Vitamin K Antagonist, Rivaroxaban, Dabigatran; Device: Any drug eluting stent oder bare metal sent; Drug: ASA, Clopidogrel, Vitamin K Antagonist, Rivaroxaban, Dabigatran

Detailed Description

The COSTA trials are investigator-initiated studies aimed at comparing the clinical outcome after percutaneous coronary intervention (PCI) using a COMBO-stent based strategy associated with short-term antiplatelet therapy with a guidelines-based therapy in patients with an indication for chronic oral anticoagulation. The study is organized as a national, multi-centre prospective, randomized trial. The duration of the follow-up is 15 months.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Chemnitz, Germany
    • MVZ am Kuechwald GmbH
  • Essen, Germany
    • Elisabeth Krankenhaus
  • Mainz, Germany
    • Universitaetsmedizin Mainz
  • Mannheim, Germany
    • UniversitaetsMedizin Mannheim
  • Mannheim, Germany
    • Theresienkrankenhaus und St. Hedwig GmbH
  • Moenchengladbach, Germany
    • St. Franziskus, Kliniken Maria Hilf GmbH
  • Muehlheim an der Ruhr, Germany
    • Evangelisches Krankenhuas Muehlheim a.d. Ruhr GmbH
  • Speyer, Germany
    • Diakonissen-Stiftungs-Krankenhaus
  • Ulm, Germany
    • Herzklinik Ulm GbR
  • Villingen-Schwenningen, Germany
    • Schwarzwald-Baar-Klinikum

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:

• Age 18 and older;
• Willingness to comply with the study protocol; subject or a legally authorized representative must provide written informed consent prior to any study related procedure, in accordance with International Conference on harmonization of Good Clinical Practice (ICH-GCP) guidelines and per site requirements.
• Patients on anticoagulant therapy or treatment-naive pa-tients with an indication to chronic anticoagulant therapy. Indications to oral anticoagulation may include atrial fibrillation, prosthetic valve disease, peripheral by-pass surgery, lung embolism or deep vein thrombosis or any other indication according to the Investigator´s opinion.
• Single or multiple de novo lesion in a native coronary artery, all amenable to treatment with the COMBO stent;

Exclusion Criteria:

• Patients who, in the Investigator's opinion, should not be treated with (N)OAC. These may include, for instance: history of BARC 3-5 bleeding <12 months; patients with a haemorrhagic disorder or bleeding diathesis (e.g. von Willebrand disease, haemophilia A or B or other hereditary bleeding disorder, history of spontaneous intra-articular bleeding, history of prolonged bleeding after surgery/intervention); patients with recent major surgery; history of intraocular, spinal, retroperitoneal, intra-articular or recent gastrointestinal bleeding unless the causative factor has been permanently eliminated or repaired; (reduction in the haemoglobin level of at least 2g/dL, transfusion of at least two units of blood, or symptomatic bleeding in a critical area or organ) including life-threatening bleeding episode (symptomatic intracranial bleeding, bleeding with a decrease in the haemoglobin level of at least 5g/dL or bleeding requiring transfusion of at least 4 units of blood or inotropic agents or necessitating surgery); Anaemia (haemoglobin <10g/dL) or thrombocytopenia including heparin-induced thrombocytopenia (platelet count <100E9/L) at screening;
• Pregnant or nursing patients. Female patients of childbearing potential must have a negative pregnancy test done within 7 days prior to the index procedure per site standard test;
• Other medical illness with a life expectancy <2 years (e.g. known malignancy) or known history of substance abuse (alcohol, cocaine, heroin etc.) that may cause non-compliance with the protocol or confound the data in-terpretation or is associated with a limited life expectancy;
• Patient has received an organ transplant or is on a wait-ing list for an organ transplant;
• Known hypersensitivity or contraindication to antiplate-let or anticoagulant agents that does not allow guide-lines-compliant therapy and that cannot be adequately pre-medicated;
• Previously received murine therapeutic antibodies and exhibited sensitization through the production of Human Anti-Murine Antibodies (HAMA);
• Any significant medical condition which in the Investigator's opinion may interfere with the patient's optimal participation in the study;
• Current participation in another investigational drug or device study except for non-interventional registries;
• Patients not willing or able to comply with the protocol requirements or considered unreliable by the Investigator concerning the requirements for follow up during the study and/or compliance with study drug administration;

Angiographic exclusion criteria:

• Vessel diameter <2 und > 5mm;
• Target lesion with characteristics that make it unsuitable for stent delivery and deployment;
• Planned use of a stent or another coronary device in the same or another session (target vessel or non-target vessel), precluding a COMBO-only strategy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: COMBO-Stent; Implantation of COMBO-Stent and medication with (N)OAC and clopidogrel for 3 months followed by (N)OAC alone	Device: COMBO-Stent; The OrbusNeich COMBO Bio-engineered Sirolimus Eluting Stent (COMBO Stent) consists of a 316L stainless steel alloy abluminally coated with a biocompatible, biodegradable poly-mer containing sirolimus. Covalently attached to the surface of the stent is a layer of murine, monoclonal, anti-human CD34 antibody. The antibody specifically targets circulatory CD34+ cells (endothelial progenitor cells) thus favoring endothelialization.; Drug: Clopidogrel, Vitamin K Antagonist, Rivaroxaban, Dabigatran; Anticoagulant medication after stent Implantation: (N)OAC and clopidogrel for 3 months followed by (N)OAC; Other Names: Plavix, Marcumar, Xarelto, Pradaxa
ACTIVE_COMPARATOR: Any Drug eluting or bare metal stent; Implantation of any drug eluting oder bare metal stent combined with anticoagulant medication according to ESC guidelines	Device: Any drug eluting stent oder bare metal sent; Implantation of traditional bare metal stents and/or drug eluting stents (any device approved on the market, implanted according to CE marking and IFU) and medication regimen in accordance with ESC Guidelines; Other Names: Cypher, Taxus, CoStar, Janus, Endeavor, Xience, Promus, Multi Link, Coroflex, Veriflex, Integrity, Driver; Drug: ASA, Clopidogrel, Vitamin K Antagonist, Rivaroxaban, Dabigatran; A combination of antiplatelet and anticoagulant therapy according to ESC guidelines (2014); Other Names: Anticoagulant medication according to ESC guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with bleedings	any BARC (bleeding academic research consortium) bleeding at 6 weeks - superiority.	6 weeks
Number of patients with safety events	Strategy oriented composite safety endpoint, including death (unless proven not to be connected to the other endpoints), any MI, stroke or systemic embolism, definite or probable stent thrombosis, BARC 3-4 bleeding at 15 months post PCI - non-inferiority with reflex to superiority testing. Hierarchical testing: Endpoint II is only tested if null hypothesis of no difference in bleeding incidence can be rejected at final analysis.	15 months

Collaborators and Investigators

• Sponsor: IHF GmbH - Institut für Herzinfarktforschung
• Collaborators: OrbusNeich
• Investigators: Principal Investigator: Tommasso Gori, Universitaetsmedizin Mainz; Principal Investigator: Ibrahim Akin, UniversitaetsMedizin Mannheim

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (ANTICIPATED): May 1, 2018
• Study Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: March 16, 2016
• First Submitted That Met QC Criteria: March 24, 2016
• First Posted (ESTIMATE): March 31, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 20, 2017
• Last Update Submitted That Met QC Criteria: February 17, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Stent , COMBO Stent, anticoagulation
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Coronary Disease; Angina Pectoris; Angina, Stable; Angina, Unstable; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Protease Inhibitors; Micronutrients; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Antifibrinolytic Agents; Hemostatics; Coagulants; Clopidogrel; Vitamin K; Rivaroxaban; Dabigatran; Vitamins; Anticoagulants
• Other Study ID Numbers: COSTA-MPG-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO