MedPath

Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD

Phase 3
Completed
Conditions
Diabetes Mellitus, Type 2
Coronary Artery Disease
Interventions
Registration Number
NCT02586155
Lead Sponsor
Resverlogix Corp
Brief Summary

The purpose of this study is to determine whether bromodomain extraterminal domain (BET) inhibition treatment with RVX000222 in high-risk type 2 diabetes mellitus patients with coronary artery disease increases the time to major adverse cardiovascular events.

Detailed Description

The majority (75%) of deaths in subjects with diabetes mellitus (DM) are due to atherosclerotic cardiovascular disease (CVD). Recent studies suggest a major adverse cardiovascular event (MACE) rate of \>11% over 18 months in type 2 diabetes mellitus (T2DM) despite a baseline LDL-C of \<2.1 mmol/L. Bromodomains (BRDs) are a family of evolutionary conserved protein-interaction modules that play key functions in chromatin organization and regulation of gene transcription. One recognized family of bromodomain-containing proteins is the bromodomain and extra-terminal (BET) family. BET inhibition represents a novel, epigenetic approach to treat CAD.

RVX000222 affects biological processes important in atherosclerosis and acute coronary events via selective inhibition of BET proteins. RVX000222 is available as a capsule formulation with standard excipients and established stability.

The BETonMACE study will focus on prevention of subsequent MACE in subjects with CAD and DM with high intensity statin therapy as co-medication.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2425
Inclusion Criteria

• ACS event of either unstable angina or myocardial infarction 7-90 days prior Visit 1:

Unstable angina: for a qualifying unstable angina event, each of components (a), (b), and (c) must be satisfied: a.) Characteristic ischemic pain or discomfort in chest/associated referral areas, occurring at rest/with minimal exertion b.) ECG changes consistent with acute myocardial ischemia based on new/presumed ST elevation/depression or T-wave inversion c.) Objective evidence of obstructive CAD based on 1+ of the following: i. New/presumed new evidence of myocardial ischemia/infarction by perfusion imaging ii. New/presumed new regional wall motion abnormality iii. Current evidence of at least 1 epicardial coronary artery stenosis ≥70% by coronary angiography iv. Need for coronary revascularization for the index ACS event, including a percutaneous coronary intervention (PCI) with or without coronary stenting.

Prior MI 7-90 days prior screening treated with or without a percutaneous coronary intervention (PCI). For a qualifying event of MI 2 of the following 3 criteria must be satisfied: a.) Characteristic ischemic chest pain/pain in associated referral areas b.) Dynamic elevation of troponin T/I or CKMB if troponinT/I is unavailable at local lab (at least >ULN for lab) c.) Development of new Q-waves in ≥2 adjacent ECG leads or development of new dominant R wave in V1

  • Documented diagnosis of T2DM (1+ of the following criteria): Documented history of T2DM, History of taking diabetes medication, and/or HbA1c ≥6.5% at Visit 1
  • For males HDL-C<40 mg/dL(1.04 mmol/L), for females HDL-C<45 mg/dL(1.17 mmol/L) at Visit 1
  • Subjects currently not on high intensity statin therapy could start rosuvastatin at Visit 1 and those currently on therapy besides atorvastatin/rosuvastatin can be switched to rosuvastatin at Visit 1
  • Female subjects of non-childbearing potential (post-surgical sterilization/post-menopausal) or if childbearing potential have neg urine pregnancy test and be willing and able to use non-hormonal birth control (non-hormonal IUD, condom or diaphragm) or remain abstinent from Screening to Follow-up Visit
  • Give signed informed consent
Exclusion Criteria
  • Heart disease which will w/in 90 days of Visit 1 likely need coronary bypass, PCI, cardiac transplantation, surgical repair and/or replacement
  • Previous/current diagnosis of severe heart failure or documented LVEF<25% determined by contrast left ventriculography, radionuclide ventriculography or echocardiography. Absence of LVEF measurement in subject w/out a previous/current diagnosis of heart failure does not exclude entry into study
  • Evidence of cardiac EP instability incl. history of uncontrolled ventricular arrhythmias, atrial fibrillation/flutter or supraventricular tachycardias w/ a ventricular response HR>100bpm at rest w/in 4 wks prior Visit 1
  • CABG w/in 90 days prior Visit 1
  • Evidence of severe renal impairment as determined by either eGFR<30 mL/min/1.7m2 at Visit 1 or current need for dialysis
  • Uncontrolled hypertension defined as 2 consecutive measurements of sitting BP of systolic>180 mmHg or diastolic>100 mmHg at Visit 1
  • Treatment w/ immunosuppressants w/in 12 mos prior Visit 1
  • Use of fibrates at any dose or niacin/nicotinic acid 250+ mg w/in 30 days prior Visit 1
  • Known allergy/sensitivity to any ingredient in IMP
  • History of intolerance to atorvastatin/rosuvastatin
  • Triglycerides>400 mg/dL (4.52 mmol/L) at Visit 1
  • Any medical/surgical condition which might significantly alter absorption, distribution, metabolism or excretion of medication
  • Evidence of cirrhosis from liver imaging/biopsy, history of hepatic encephalopathy, esophageal/gastric varices, active hepatitis or prior porta-caval shunt procedure or a Child-Pugh score of ≥5 points
  • ALT/AST>1.5xULN by central lab at Visit 1
  • Tot. bilirubin>ULN by central lab at Visit 1
  • History of malignancy of any organ syst treated/untreated w/in the past 2 yrs whether or not there is evidence of local recurrence/metastases except localized basal skin cell carcinoma
  • History/evidence of drug/alcohol abuse w/in 12 mos of Visit 1
  • Pregnancy
  • Any condition which may place subject at higher risk from his/her participation in the study or is likely to prevent subject from completing/complying w/ requirements of study
  • Use of other investigational drugs and devices w/in 30 days or 5 half-lives of Visit 1, whichever is longer
  • History of noncompliance to medical regimens or unwillingness to comply w/ study protocol
  • Any condition that would confound the evaluation/interpretation of efficacy and/or safety data
  • Persons directly involved in execution of this protocol

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
High-Intensity statin therapy+RVX000222AtorvastatinDaily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)
High-Intensity statin therapy+PlaceboPlaceboPlacebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)
High-Intensity statin therapy+RVX000222ApabetaloneDaily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)
High-Intensity statin therapy+RVX000222RosuvastatinDaily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)
High-Intensity statin therapy+PlaceboAtorvastatinPlacebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)
High-Intensity statin therapy+PlaceboRosuvastatinPlacebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)
Primary Outcome Measures
NameTimeMethod
Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE120 weeks

Incidence of first occurrence of MACE narrowly defined as a single composite endpoint of Cardiovascular (CV) Death (including undetermined cause of death) or Non-fatal Myocardial Infarction (MI) or Stroke. If a subject has multiple events, only the first event contributing to the composite endpoint is counted.

Secondary Outcome Measures
NameTimeMethod
Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE120 weeks

First occurrence of MACE broadly defined as a single composite endpoint of Cardiovascular Death (CVD) (including undetermined cause of death) or Non-fatal Myocardial Infarction (MI), Stroke, or Hospitalization for CVD events (including unstable angina and evidence of new or presumed new progressive obstructive coronary disease or emergency revascularization procedures at any time and urgent revascularization procedures ≥30 days after the index event as defined by Hicks et al., 2014) . If a subject has multiple events, only the first event contributing to the composite endpoint is counted.

Incidence of Hospitalization for Congestive Heart Failure (CHF)120 weeks
Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline Over Time Within and Between Treatment Groups for Subjects With Impaired Renal Function at Baseline (eGFR <60 mL/Min/1.7m2)120 weeks
Incidence of All-cause Mortality120 weeks
Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups120 weeks
Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups120 weeks
Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups120 weeks
Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups120 weeks
Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups120 weeks
Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups120 weeks
Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups52 weeks
Change in Glucose From Baseline Over Time Between and Within Treatment Groups120 weeks
Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups172 weeks

Trial Locations

Locations (213)

Clinical Hospital Sveti duh

🇭🇷

Zagreb, Croatia

AZ Turnhout

🇧🇪

Turnhout, Belgium

Kaplan Medical Center

🇮🇱

Rehovot, Israel

Studienzentrum Dr.Appel

🇩🇪

Kassel, Germany

ZNA Middelheim

🇧🇪

Antwerpen, Belgium

Instituto Cardiovascular de Buenos Aires

🇦🇷

Buenos Aires, Argentina

Centro Médico Colón

🇦🇷

Córdoba, Argentina

Multiprofile Hospital For Active Treatment - Dr. Bratan Shukerov AD

🇧🇬

Smolyan, Bulgaria

Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda

🇧🇬

Sofia, Bulgaria

University Multiprofile Hospital for Active Treatment Aleksandrovska EAD

🇧🇬

Sofia, Bulgaria

Instituto de Investigaciones Clinicas Bahia Blanca

🇦🇷

Bahía Blanca, Argentina

Centro Privado de Enfermedades Cardiovasculares

🇦🇷

Buenos Aires, Argentina

Sanatorio Guemes

🇦🇷

Buenos Aires, Argentina

Flinders Medical Centre

🇦🇺

Bedford Park, Australia

Second Multiprofile Hospital for Active Treatment Sofia

🇧🇬

Sofia, Bulgaria

Medical Center Orfey OOD

🇧🇬

Stara Zagora, Bulgaria

DRK Kliniken Berlin Westend

🇩🇪

Berlin, Germany

Bioclinica Buenos Aires

🇦🇷

Buenos Aires, Argentina

Centro Médico Luquez

🇦🇷

Córdoba, Argentina

Asklepios Klinik Langen

🇩🇪

Langen, Germany

Clinical Hospital Osijek

🇭🇷

Osijek, Croatia

Clinica Coronel Suarez

🇦🇷

Coronel Suárez, Argentina

Sanatorio Allende

🇦🇷

Córdoba, Argentina

Hospital Cordoba

🇦🇷

Córdoba, Argentina

Instituto Modelo de Cardiologia

🇦🇷

Córdoba, Argentina

Multiprofile Hospital For Active Treatment Dr Tota Venkova

🇧🇬

Gabrovo, Bulgaria

Heidelberger Praxisklinik für Kardiologie

🇩🇪

Heidelberg, Germany

General Hospital Karlovac

🇭🇷

Karlovac, Croatia

Special Hospital for medicinal rehabilitation Krapinske Toplice

🇭🇷

Krapinske Toplice, Croatia

Imelda VZW

🇧🇪

Bonheiden, Belgium

Consultorios Asociados Endocronología E Investigación Clínica Aplicada

🇦🇷

Buenos Aires, Argentina

Hospital San Roque

🇦🇷

Córdoba, Argentina

Multiprofile Hospital For Active Treatment - Pazardzhik AD

🇧🇬

Pazardzhik, Bulgaria

Klinikum Hoyerswerda

🇩🇪

Hoyerswerda, Germany

Unidad de Investigacion Clinica Cardiometabolica de Occidente SC

🇲🇽

Guadalajara, Mexico

General Hospital Virovitica

🇭🇷

Virovitica, Croatia

Polsko-Amerykanskie Kliniki Serca

🇵🇱

Nysa, Poland

Szpital Specjalistyczny im. Jozefa Dietla w Krakowie

🇵🇱

Kraków, Poland

City Clinic University Multiprofile Hospital for Active Treatment EOOD

🇧🇬

Sofia, Bulgaria

Medical Center Kardiohelp EOOD

🇧🇬

Sofia, Bulgaria

Medizinisches Versorgungszentrum am Küchwald GmbH

🇩🇪

Chemnitz, Germany

Katholisches Krankenhaus St. Johann Nepomuk

🇩🇪

Erfurt, Germany

Rodzinne Centrum Zdrowia

🇵🇱

Otwock, Poland

Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet

🇭🇺

Budapest, Hungary

Investigacion en Salud y Metabolismo S.C.

🇲🇽

Chihuahua, Mexico

Fundación de Atención e Investigación Médica Lindavista S.C.

🇲🇽

Ciudad de México, Mexico

Malopolskie Centrum Sercowo-Naczyniowe

🇵🇱

Chrzanow, Poland

VU Medisch Centrum

🇳🇱

Amsterdam, Netherlands

Pro Corde, Dom Medyczny

🇵🇱

Opole, Poland

TaNaMed Kft.

🇭🇺

Mosonmagyaróvár, Hungary

Edith Wolfson Medical Center

🇮🇱

Holon, Israel

Meir Medical Center

🇮🇱

Kefar-Sava, Israel

Galilee Medical Center

🇮🇱

Nahariya, Israel

Hadassah University Hospital Mount Scopus

🇮🇱

Jerusalem, Israel

Clinica Integral del Paciente Diabetico y Obeso

🇲🇽

Ciudad De México, Mexico

Unidad de Investigación Clínica En Medicina SC

🇲🇽

Monterrey, Mexico

Niepubliczny Zaklad Opieki Zdrowotnej Centrum Uslug Medycznych Promont-Med.

🇵🇱

Kielce, Poland

Soroka University Medical Centre

🇮🇱

Be'er Sheva, Israel

Linn Medical Center Clalit Health Services

🇮🇱

Haifa, Israel

Clalit Health Medical Center

🇮🇱

Tel Aviv, Israel

City Hospital 13

🇷🇺

Nizhniy Novgorod, Russian Federation

Centro de Investigación Biomedica y Farmaceutica

🇲🇽

Ciudad de México, Mexico

Podlaski Osrodek Kardiologii Poradnia Prywatna

🇵🇱

Bialystok, Poland

Diamond Clinic

🇵🇱

Kraków, Poland

Zespol Przychodni Specjalistycznych DIAB-END-COR Sp. z o.o.

🇵🇱

Kraków, Poland

Chaim Sheba Medical Center

🇮🇱

Ramat Gan, Israel

Meander Medisch Centrum

🇳🇱

Amersfoort, Netherlands

Hospital Cardiológica Aguascalientes

🇲🇽

Aguascalientes, Mexico

Instituto Cardiovascular de Monclova

🇲🇽

Monclova, Mexico

Centrum Medyczne doktorA

🇵🇱

Warszawa, Poland

Kanizsai Dorottya Kórház

🇭🇺

Nagykanizsa, Hungary

Bnei Zion Medical Center

🇮🇱

Haifa, Israel

ZIV Medical Center

🇮🇱

Safed, Israel

Cardioinvest s. r. o.

🇸🇰

Nove Zamky, Slovakia

Niepubliczny Zaklad Opieki Zdrowotnej Specjalistyczna Przychodnia Lekarska "MEDIKARD"

🇵🇱

Plock, Poland

Clinical Centre of Vojvodina

🇷🇸

Novi Sad, Serbia

St Petersburg City Outpatient Clinic #109

🇷🇺

Saint Petersburg, Russian Federation

KARDIOMED s.r.o.

🇸🇰

Lucenec, Slovakia

Changhua Christian Hospital

🇨🇳

Changhua, Taiwan

Mackay Memorial Hospital-Taipei branch

🇨🇳

New Taipei City, Taiwan

Centro de Investigacion y Atencion de Diabetes, Endocrinologia y Nutricion

🇲🇽

Durango, Mexico

Investigacion Biomedica Aplicada de Hidalgo S.A. de C.V.

🇲🇽

Pachuca, Mexico

Fundacion Cardiovascular de Aguascalientes AC

🇲🇽

Aguascalientes, Mexico

General Hospital Uzice

🇷🇸

Uzice, Serbia

MEDI M&M s.r.o.

🇸🇰

Moldava nad Bodvou, Slovakia

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

Arechavaleta Granell Maria del Rosario

🇲🇽

Guadalajara, Mexico

Hospital Universitario Dr. Jose Eleuterio González

🇲🇽

Monterrey, Mexico

Diabetes Total, S.A de C.V.

🇲🇽

Pachuca, Mexico

Centro de Alta Especialidad Dr. Rafael Lucio

🇲🇽

Veracruz, Mexico

Clinical Hospital Center Bezanijska Kosa

🇷🇸

Belgrade, Serbia

Clinical Hospital Centre Zemun

🇷🇸

Belgrade, Serbia

Institute Niska Banja

🇷🇸

Niska Banja, Serbia

Univerzitna nemocnica Bratislava

🇸🇰

Bratislava, Slovakia

DIAB s.r.o.

🇸🇰

Roznava, Slovakia

Chang Gung Medical Foundation Linkou Branch (Clinical Research Center)

🇨🇳

Taoyuan City, Taiwan

Chi Mei Medical Center

🇨🇳

Taipei, Taiwan

Centro de Desarrollo Biomédico

🇲🇽

Merida, Mexico

Centro Para el Desarrollo de la Medicina y de Asistencia Especializada SC

🇲🇽

Culiacan, Mexico

Dr. Humberto Alvarez Lopez

🇲🇽

Zapopan, Mexico

Hospital Central Dr Ignacio Morones Prieto

🇲🇽

San Luis Potosí, Mexico

Cardioarritmias e Investigación S.C.

🇲🇽

San Luis Potosi, Mexico

Far Eastern Memorial Hospital

🇨🇳

Taipei, Taiwan

INBIOMEDYC Toluca

🇲🇽

Toluca, Mexico

Health Center Zajecar

🇷🇸

Zajecar, Serbia

Clinical Center Kragujevac

🇷🇸

Kragujevac, Serbia

Kaohsiung Chang Gung Memorial Hospital

🇨🇳

Kaohsiung, Taiwan

Zentrum für Klinische Prüfung in der Facharztzentrum Dresden Neustadt Gbr

🇩🇪

Dresden, Germany

Klinikum Leverkusen GmbH

🇩🇪

Leverkusen, Germany

Research Cardiology Institute of Tomsk Scientific Center of RAMS Siberian Branch

🇷🇺

Tomsk, Russian Federation

Multiprofile Hospital for Active Treatment - Prof. Dr. Paraskev Stoyanov AD

🇧🇬

Lovech, Bulgaria

Synexus Affiliate - Diagnostic and Consulting Center Ascendent

🇧🇬

Sofia, Bulgaria

Multiprofile Hospital for Active Treatment Sveta Marina EAD

🇧🇬

Varna, Bulgaria

Hadassah University Hospital Ein Kerem

🇮🇱

Jerusalem, Israel

Hillel Yaffe Medical Center

🇮🇱

Hadera, Israel

Tel Aviv Sourasky Medical Center

🇮🇱

Tel-Aviv, Israel

Baruch Padeh Poriya Medical Center

🇮🇱

Tiberias, Israel

Centro Médico Libertad

🇦🇷

Haedo, Argentina

Instituto de Cardiologia de Corrientes Juana Francisca Cabral

🇦🇷

Corrientes, Argentina

CEMAIC

🇦🇷

Córdoba, Argentina

Clínica Privada Del Prado Sociedad de Responsabilidad Limitada

🇦🇷

Córdoba, Argentina

Fundación Clínica Colombo

🇦🇷

Córdoba, Argentina

Instituto Del Corazón

🇦🇷

Córdoba, Argentina

CIMEL

🇦🇷

Lanús, Argentina

Instituto de Investigaciones Clínicas Mar Del Plata

🇦🇷

Mar Del Plata, Argentina

DIM Clinica Privada

🇦🇷

Ramos Mejia, Argentina

Hospital Central

🇦🇷

Mendoza, Argentina

Instituto de Hematologia Y Medicina Clinica

🇦🇷

Rosario, Argentina

Sanatorio Britanico de Rosario

🇦🇷

Rosario, Argentina

Centro Modelo de Cardiologia

🇦🇷

San Miguel De Tucumán, Argentina

Investigaciones Clinicas Tucuman

🇦🇷

San Miguel De Tucumán, Argentina

Grupo Medico Alem

🇦🇷

San Isidro, Argentina

Bioclinica Tucumán

🇦🇷

San Miguel De Tucumán, Argentina

Centro de Investigaciones Clínicas Del Litoral SRL

🇦🇷

Santa Fe, Argentina

Sanatorio San Francisco

🇦🇷

Santiago Del Estero, Argentina

Instituto de Investigaciones Clínicas Zárate

🇦🇷

Zárate, Argentina

Bajai Szent Rókus Kórház

🇭🇺

Baja, Hungary

Semmelweis Egyetem

🇭🇺

Budapest, Hungary

Selye János Kórház

🇭🇺

Komárom, Hungary

Bajcsy-Zsilinszky Korhaz es Rendelointezet

🇭🇺

Budapest, Hungary

Gottsegen Gyorgy Orszagos Kardiologiai Intezet

🇭🇺

Budapest, Hungary

Magyar Honvédség Egészségügyi Központ

🇭🇺

Budapest, Hungary

Synexus (DRS) - Synexus Magyarország Kft. Budapest

🇭🇺

Budapest, Hungary

Tolna Megyei Balassa János Kórház

🇭🇺

Szekszárd, Hungary

Instituto Médico DAMIC

🇦🇷

Córdoba, Argentina

Szent Margit Korhaz

🇭🇺

Budapest, Hungary

Nazareth EMMS Hospital

🇮🇱

Nazareth, Israel

Clínica FUSAVIM Privada

🇦🇷

Villa María, Argentina

Ipac Caraffa

🇦🇷

Córdoba, Argentina

Prevencion Cardio Vascular

🇦🇷

Salta, Argentina

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

🇭🇺

Szeged, Hungary

Barzilai Medical Center

🇮🇱

Ashkelon, Israel

Lady Davis Carmel Medical Center

🇮🇱

Haifa, Israel

University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski EAD

🇧🇬

Pleven, Bulgaria

University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD

🇧🇬

Sofia, Bulgaria

Grof Tisza Istvan Korhaz Berettyoujfalu

🇭🇺

Berettyóújfalu, Hungary

Szent Rókus Kórház és Intézményei

🇭🇺

Budapest, Hungary

Coromed-SMO Kft.

🇭🇺

Pécs, Hungary

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz

🇭🇺

Székesfehérvár, Hungary

Rambam Medical Center

🇮🇱

Haifa, Israel

Shaare Zedek Medical Center

🇮🇱

Jerusalem, Israel

Centro de Investigacion Medica Biologica Y de Terapia Avanzada SC

🇲🇽

Guadalajara, Mexico

Hospital Angeles Leon

🇲🇽

León De Los Aldama, Mexico

Sanatorio y Servicios Médicos Obregón S.A. de C.V.

🇲🇽

Mexico City, Mexico

IMED Internal Medicine Clin Trials

🇲🇽

Monterrey, Mexico

Gabinet Kardiologiczno-Internistyczny

🇵🇱

Gdynia, Poland

OLVG locatie Oost

🇳🇱

Amsterdam, Netherlands

Uniwersytecki Szpital Kliniczny im. Wojskowej Akademii Medycznej Centralny Szpital Weteranow

🇵🇱

Lódz, Poland

Medicome Sp. z o.o.

🇵🇱

Oswiecim, Poland

Prywatna Praktyka Lekarska MAZ-MEDICA Maciej R.Mazurkiewicz

🇵🇱

Lodz, Poland

Niepubliczny Zaklad Opieki Zdrowotnej Centrum Medyczne SBB

🇵🇱

Tarnobrzeg, Poland

Centrum Kardiologiczne Pro Corde Sp. z o.o. Niepubliczny Zaklad Opieki Zdrowotnej

🇵🇱

Wroclaw, Poland

Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego

🇵🇱

Warszawa, Poland

Wro Medica

🇵🇱

Wroclaw, Poland

City Clinical Hospital #6

🇷🇺

Chelyabinsk, Russian Federation

Ural State Medical University

🇷🇺

Ekaterinburg, Russian Federation

Federal Budget Healthcare Institution Medici - sanitary unit of Ministry of internal affairs of Russ

🇷🇺

Kemerovo, Russian Federation

Research Institute of Complex Cardiovascular Pathology

🇷🇺

Kemerovo, Russian Federation

Krasnodar Regional Clinical Hospital #2

🇷🇺

Krasnodar, Russian Federation

Moscow City State Budgetary Healthcare Institution City Clinical Hospital named after V.V. Veresayev

🇷🇺

Moscow, Russian Federation

Russian Cardiology Research and Production Center

🇷🇺

Moscow, Russian Federation

Republican Hospital n.a. V.A. Baranov

🇷🇺

Petrozavodsk, Russian Federation

Municipal Budgetary Healthcare Institution City Emergency Hospital

🇷🇺

Rostov-on-Don, Russian Federation

State Budgetary Healthcare Institution of Novosibirsk Region City Clinical Hospital No. 19

🇷🇺

Novosibirsk, Russian Federation

International Medical Center SOGAZ

🇷🇺

Saint Petersburg, Russian Federation

Saratov State Medical University

🇷🇺

Saratov, Russian Federation

North-West State Medical University n.a. I.I. Mechnikov

🇷🇺

Saint Petersburg, Russian Federation

State Healthcare Institution Regional Clinical Cardiologic Dispensary

🇷🇺

Saratov, Russian Federation

City Hospital #4

🇷🇺

Sochi, Russian Federation

Clinical Center of Serbia

🇷🇸

Belgrade, Serbia

State Budgetary Healthcare Institution of Vladimir Region City Hospital No. 4

🇷🇺

Vladimir, Russian Federation

Clinical Hospital Centar Zvezdara

🇷🇸

Belgrade, Serbia

Euromedik

🇷🇸

Belgrade, Serbia

Institute of Cardiovascular Diseases Dedinje

🇷🇸

Belgrade, Serbia

Military Medical Academy

🇷🇸

Belgrade, Serbia

KBC Dr Dragisa Misovic Dedinje

🇷🇸

Belgrade, Serbia

Clinical Center Nis

🇷🇸

Nis, Serbia

Institute of Cardiovascular Diseases of Vojvodina

🇷🇸

Sremska Kamenica, Serbia

ALIAN, s.r.o

🇸🇰

Bardejov, Slovakia

CARDIOCONSULT, s.r.o.

🇸🇰

Bratislava, Slovakia

Kardio-Onkologia, s.r.o.

🇸🇰

Dolny Kubin, Slovakia

CARDIO D&R, s.r.o. Kosice

🇸🇰

Kosice, Slovakia

Zeleznicne zdravotnictvo Kosice, s.r.o.

🇸🇰

Kosice, Slovakia

Nemocnica s poliklinikou Nove Mesto nad Vahom n.o.

🇸🇰

Nove Mesto nad Vahom, Slovakia

MEDIVASA, s.r.o.

🇸🇰

Zilina, Slovakia

Kaohsiung Veterans General Hospital

🇨🇳

Kaohsiung, Taiwan

China Medical University Hospital

🇨🇳

Taichung, Taiwan

National Cheng Kung University Hospital

🇨🇳

Tainan City, Taiwan

Tri-Service General Hospital

🇨🇳

Taipei City, Taiwan

Cathay General Hospital

🇨🇳

Taipei, Taiwan

Taipei Veterans General Hospital

🇨🇳

Taipei, Taiwan

General Hospital Dr Josip Bencevic

🇭🇷

Slavonski Brod, Croatia

Niepubliczny Zaklad Opieki Zdrowotnej AURUM

🇵🇱

Warszawa, Poland

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