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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Stable Angina, Unstable Angina, STEMI, NSTEMI, Coronary Disease

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COMBO-Stent<br>Implantation of COMBO-Stent and medication with (N)OAC and clopidogrel for 3 months followed by (N)OAC alone | Device: COMBO-Stent<br>* 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.<br>Drug: Clopidogrel, Vitamin K Antagonist, Rivaroxaban, Dabigatran<br>* Anticoagulant medication after stent Implantation: (N)OAC and clopidogrel for 3 months followed by (N)OAC<br>* Other names: Plavix, Marcumar, Xarelto, Pradaxa;|
| Active Comparator: Any Drug eluting or bare metal stent<br>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<br>* 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<br>* Other names: Cypher, Taxus, CoStar, Janus, Endeavor, Xience, Promus, Multi Link, Coroflex, Veriflex, Integrity, Driver;Drug: ASA, Clopidogrel, Vitamin K Antagonist, Rivaroxaban, Dabigatran<br>* A combination of antiplatelet and anticoagulant therapy according to ESC guidelines (2014)<br>* Other names: Anticoagulant medication according to ESC guidelines;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stent , COMBO Stent, anticoagulation