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

NCT02723981 | Withdrawn Phase 4 DMC

• 1 other identifier: COSTA-MPG-001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Stable Angina; Unstable Angina; STEMI; NSTEMI; Coronary Disease

Keywords

Stent , COMBO Stent, anticoagulation

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

COMBO-Stent

EXPERIMENTAL

Implantation of COMBO-Stent and medication with (N)OAC and clopidogrel for 3 months followed by (N)OAC alone

Device: COMBO-Stent; Drug: Clopidogrel, Vitamin K Antagonist, Rivaroxaban, Dabigatran

Any Drug eluting or bare metal stent

ACTIVE COMPARATOR

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; Drug: ASA, Clopidogrel, Vitamin K Antagonist, Rivaroxaban, Dabigatran

Interventions

COMBO-Stent DEVICE

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.

COMBO-Stent

Clopidogrel, Vitamin K Antagonist, Rivaroxaban, Dabigatran DRUG

Anticoagulant medication after stent Implantation: (N)OAC and clopidogrel for 3 months followed by (N)OAC

Also known as: Plavix, Marcumar, Xarelto, Pradaxa

COMBO-Stent

Any drug eluting stent oder bare metal sent DEVICE

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

Also known as: Cypher, Taxus, CoStar, Janus, Endeavor, Xience, Promus, Multi Link, Coroflex, Veriflex, Integrity, Driver

Any Drug eluting or bare metal stent

ASA, Clopidogrel, Vitamin K Antagonist, Rivaroxaban, Dabigatran DRUG

A combination of antiplatelet and anticoagulant therapy according to ESC guidelines (2014)

Also known as: Anticoagulant medication according to ESC guidelines

Any Drug eluting or bare metal stent

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• IHF GmbH - Institut für Herzinfarktforschung: lead
• OrbusNeich: collaborator

Study Sites (10)

MVZ am Kuechwald GmbH

Chemnitz, Germany

Location

Elisabeth Krankenhaus

Essen, Germany

Location

Universitaetsmedizin Mainz

Mainz, Germany

Location

Theresienkrankenhaus und St. Hedwig GmbH

Mannheim, Germany

Location

Universitaetsmedizin Mannheim

Mannheim, Germany

Location

St. Franziskus, Kliniken Maria Hilf GmbH

Mönchengladbach, Germany

Location

Evangelisches Krankenhuas Muehlheim a.d. Ruhr GmbH

Muehlheim An Der Ruhr, Germany

Location

Diakonissen-Stiftungs-Krankenhaus

Speyer, Germany

Location

Herzklinik Ulm GbR

Ulm, Germany

Location

Schwarzwald-Baar-Klinikum

Villingen-Schwenningen, Germany

Location

MeSH Terms

Conditions

Angina, Stable; Angina, Unstable; ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Coronary Disease

Interventions

Clopidogrel; Rivaroxaban; Dabigatran; Phenprocoumon

Condition Hierarchy (Ancestors)

Angina Pectoris; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Necrosis

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Morpholines; Oxazines; Benzimidazoles; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans

Study Officials

• Tommasso Gori

  Universitaetsmedizin Mainz

  PRINCIPAL INVESTIGATOR

• Ibrahim Akin

  Universitaetsmedizin Mannheim

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 31, 2016
• Study Start: April 1, 2016
• Primary Completion: May 1, 2018
• Study Completion: December 1, 2018
• Last Updated: February 20, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (10)