Clinical trial NCT02586155: Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD
Official title: A Phase III Multi-Center, Double-Blind, Randomized, Parallel Group, Placebo-Controlled Clinical Trial in High-Risk Type 2 Diabetes Mellitus (T2DM) Subjects With Coronary Artery Disease (CAD) to Determine Whether Bromodomain Extraterminal Domain (BET) Inhibition Treatment With RVX000222 Increases the Time to Major Adverse Cardiovascular Events (MACE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Coronary Artery Disease
Lead sponsor: Resverlogix Corp
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
name: ICON plc
name: Medidata Solutions
First posted: 2015-10-26
Enrollment: 2425
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE
timeFrame: 120 weeks
Secondary outcomes:
measure: Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE
timeFrame: 120 weeks
measure: Incidence of Hospitalization for Congestive Heart Failure (CHF)
timeFrame: 120 weeks
measure: Incidence of All-cause Mortality
timeFrame: 120 weeks
measure: Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups
timeFrame: 120 weeks
measure: Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups
timeFrame: 120 weeks
measure: Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups
timeFrame: 120 weeks
measure: Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups
timeFrame: 120 weeks
measure: Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups
timeFrame: 120 weeks
measure: Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups
timeFrame: 120 weeks
measure: Change in Glucose From Baseline Over Time Between and Within Treatment Groups
timeFrame: 120 weeks
measure: Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups
timeFrame: 172 weeks
measure: Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups
timeFrame: 52 weeks
measure: 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)
timeFrame: 120 weeks
Other outcomes:
Locations:
city: Bahía Blanca
country: Argentina
facility: Instituto de Investigaciones Clinicas Bahia Blanca
city: Buenos Aires
country: Argentina
facility: Bioclinica Buenos Aires
city: Buenos Aires
country: Argentina
facility: Centro Privado de Enfermedades Cardiovasculares
city: Buenos Aires
country: Argentina
facility: Consultorios Asociados Endocronología E Investigación Clínica Aplicada
city: Buenos Aires
country: Argentina
facility: Instituto Cardiovascular de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Sanatorio Guemes
city: Coronel Suárez
country: Argentina
facility: Clinica Coronel Suarez
city: Corrientes
country: Argentina
facility: Instituto de Cardiologia de Corrientes Juana Francisca Cabral
city: Córdoba
country: Argentina
facility: CEMAIC
city: Córdoba
country: Argentina
facility: Centro Médico Colón
city: Córdoba
country: Argentina
facility: Centro Médico Luquez
city: Córdoba
country: Argentina
facility: Clínica Privada Del Prado Sociedad de Responsabilidad Limitada
city: Córdoba
country: Argentina
facility: Fundación Clínica Colombo
city: Córdoba
country: Argentina
facility: Hospital Cordoba
city: Córdoba
country: Argentina
facility: Hospital San Roque
city: Córdoba
country: Argentina
facility: Instituto Del Corazón
city: Córdoba
country: Argentina
facility: Instituto Modelo de Cardiologia
city: Córdoba
country: Argentina
facility: Instituto Médico DAMIC
city: Córdoba
country: Argentina
facility: Ipac Caraffa
city: Córdoba
country: Argentina
facility: Sanatorio Allende
city: Haedo
country: Argentina
facility: Centro Médico Libertad
city: Lanús
country: Argentina
facility: CIMEL
city: Mar Del Plata
country: Argentina
facility: Instituto de Investigaciones Clínicas Mar Del Plata
city: Mendoza
country: Argentina
facility: Hospital Central
city: Ramos Mejia
country: Argentina
facility: DIM Clinica Privada
city: Rosario
country: Argentina
facility: Instituto de Hematologia Y Medicina Clinica
city: Rosario
country: Argentina
facility: Sanatorio Britanico de Rosario
city: Salta
country: Argentina
facility: Prevencion Cardio Vascular
city: San Isidro
country: Argentina
facility: Grupo Medico Alem
city: San Miguel De Tucumán
country: Argentina
facility: Bioclinica Tucumán
city: San Miguel De Tucumán
country: Argentina
facility: Centro Modelo de Cardiologia
city: San Miguel De Tucumán
country: Argentina
facility: Investigaciones Clinicas Tucuman
city: Santa Fe
country: Argentina
facility: Centro de Investigaciones Clínicas Del Litoral SRL
city: Santiago Del Estero
country: Argentina
facility: Sanatorio San Francisco
city: Villa María
country: Argentina
facility: Clínica FUSAVIM Privada
city: Zárate
country: Argentina
facility: Instituto de Investigaciones Clínicas Zárate
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Bonheiden
country: Belgium
facility: Imelda VZW
city: Turnhout
country: Belgium
facility: AZ Turnhout
city: Gabrovo
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment Dr Tota Venkova
city: Lovech
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Prof. Dr. Paraskev Stoyanov AD
city: Pazardzhik
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment - Pazardzhik AD
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski EAD
city: Smolyan
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment - Dr. Bratan Shukerov AD
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda
city: Sofia
country: Bulgaria
facility: City Clinic University Multiprofile Hospital for Active Treatment EOOD
city: Sofia
country: Bulgaria
facility: Medical Center Kardiohelp EOOD
city: Sofia
country: Bulgaria
facility: Second Multiprofile Hospital for Active Treatment Sofia
city: Sofia
country: Bulgaria
facility: Synexus Affiliate - Diagnostic and Consulting Center Ascendent
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD
city: Stara Zagora
country: Bulgaria
facility: Medical Center Orfey OOD
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Sveta Marina EAD
city: Karlovac
country: Croatia
facility: General Hospital Karlovac
city: Krapinske Toplice
country: Croatia
facility: Special Hospital for medicinal rehabilitation Krapinske Toplice
city: Osijek
country: Croatia
facility: Clinical Hospital Osijek
city: Slavonski Brod
country: Croatia
facility: General Hospital Dr Josip Bencevic
city: Virovitica
country: Croatia
facility: General Hospital Virovitica
city: Zagreb
country: Croatia
facility: Clinical Hospital Sveti duh
city: Berlin
country: Germany
facility: DRK Kliniken Berlin Westend
city: Chemnitz
country: Germany
facility: Medizinisches Versorgungszentrum am Küchwald GmbH
city: Dresden
country: Germany
facility: Zentrum für Klinische Prüfung in der Facharztzentrum Dresden Neustadt Gbr
city: Erfurt
country: Germany
facility: Katholisches Krankenhaus St. Johann Nepomuk
city: Heidelberg
country: Germany
facility: Heidelberger Praxisklinik für Kardiologie
city: Hoyerswerda
country: Germany
facility: Klinikum Hoyerswerda
city: Kassel
country: Germany
facility: Studienzentrum Dr.Appel
city: Langen
country: Germany
facility: Asklepios Klinik Langen
city: Leverkusen
country: Germany
facility: Klinikum Leverkusen GmbH
city: Baja
country: Hungary
facility: Bajai Szent Rókus Kórház
city: Berettyóújfalu
country: Hungary
facility: Grof Tisza Istvan Korhaz Berettyoujfalu
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Korhaz es Rendelointezet
city: Budapest
country: Hungary
facility: Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet
city: Budapest
country: Hungary
facility: Gottsegen Gyorgy Orszagos Kardiologiai Intezet
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Synexus (DRS) - Synexus Magyarország Kft. Budapest
city: Budapest
country: Hungary
facility: Szent Margit Korhaz
city: Budapest
country: Hungary
facility: Szent Rókus Kórház és Intézményei
city: Komárom
country: Hungary
facility: Selye János Kórház
city: Mosonmagyaróvár
country: Hungary
facility: TaNaMed Kft.
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Kórház
city: Pécs
country: Hungary
facility: Coromed-SMO Kft.
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
city: Szekszárd
country: Hungary
facility: Tolna Megyei Balassa János Kórház
city: Székesfehérvár
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Centre
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Bnei Zion Medical Center
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Haifa
country: Israel
facility: Linn Medical Center Clalit Health Services
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Holon
country: Israel
facility: Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Mount Scopus
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Kefar-Sava
country: Israel
facility: Meir Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Nazareth
country: Israel
facility: Nazareth EMMS Hospital
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Safed
country: Israel
facility: ZIV Medical Center
city: Tel Aviv
country: Israel
facility: Clalit Health Medical Center
city: Tel-Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tiberias
country: Israel
facility: Baruch Padeh Poriya Medical Center
city: Aguascalientes
country: Mexico
facility: Fundacion Cardiovascular de Aguascalientes AC
city: Aguascalientes
country: Mexico
facility: Hospital Cardiológica Aguascalientes
city: Chihuahua
country: Mexico
facility: Investigacion en Salud y Metabolismo S.C.
city: Ciudad de México
country: Mexico
facility: Centro de Investigación Biomedica y Farmaceutica
city: Ciudad De México
country: Mexico
facility: Clinica Integral del Paciente Diabetico y Obeso
city: Ciudad de México
country: Mexico
facility: Fundación de Atención e Investigación Médica Lindavista S.C.
city: Culiacan
country: Mexico
facility: Centro Para el Desarrollo de la Medicina y de Asistencia Especializada SC
city: Durango
country: Mexico
facility: Centro de Investigacion y Atencion de Diabetes, Endocrinologia y Nutricion
city: Guadalajara
country: Mexico
facility: Arechavaleta Granell Maria del Rosario
city: Guadalajara
country: Mexico
facility: Centro de Investigacion Medica Biologica Y de Terapia Avanzada SC
city: Guadalajara
country: Mexico
facility: Unidad de Investigacion Clinica Cardiometabolica de Occidente SC
city: León De Los Aldama
country: Mexico
facility: Hospital Angeles Leon
city: Merida
country: Mexico
facility: Centro de Desarrollo Biomédico
city: Mexico City
country: Mexico
facility: Sanatorio y Servicios Médicos Obregón S.A. de C.V.
city: Monclova
country: Mexico
facility: Instituto Cardiovascular de Monclova
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio González
city: Monterrey
country: Mexico
facility: IMED Internal Medicine Clin Trials
city: Monterrey
country: Mexico
facility: Unidad de Investigación Clínica En Medicina SC
city: Pachuca
country: Mexico
facility: Diabetes Total, S.A de C.V.
city: Pachuca
country: Mexico
facility: Investigacion Biomedica Aplicada de Hidalgo S.A. de C.V.
city: San Luis Potosi
country: Mexico
facility: Cardioarritmias e Investigación S.C.
city: San Luis Potosí
country: Mexico
facility: Hospital Central Dr Ignacio Morones Prieto
city: Toluca
country: Mexico
facility: INBIOMEDYC Toluca
city: Veracruz
country: Mexico
facility: Centro de Alta Especialidad Dr. Rafael Lucio
city: Zapopan
country: Mexico
facility: Dr. Humberto Alvarez Lopez
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: OLVG locatie Oost
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Bialystok
country: Poland
facility: Podlaski Osrodek Kardiologii Poradnia Prywatna
city: Chrzanow
country: Poland
facility: Malopolskie Centrum Sercowo-Naczyniowe
city: Dabrowa Gornicza
country: Poland
facility: Polsko-Amerykanskie Kliniki Serca
city: Gdynia
country: Poland
facility: Gabinet Kardiologiczno-Internistyczny
city: Kielce
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Centrum Uslug Medycznych Promont-Med.
city: Kraków
country: Poland
facility: Diamond Clinic
city: Kraków
country: Poland
facility: Szpital Specjalistyczny im. Jozefa Dietla w Krakowie
city: Kraków
country: Poland
facility: Zespol Przychodni Specjalistycznych DIAB-END-COR Sp. z o.o.
city: Lodz
country: Poland
facility: Prywatna Praktyka Lekarska MAZ-MEDICA Maciej R.Mazurkiewicz
city: Lódz
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Wojskowej Akademii Medycznej Centralny Szpital Weteranow
city: Nysa
country: Poland
facility: Polsko-Amerykanskie Kliniki Serca
city: Opole
country: Poland
facility: Pro Corde, Dom Medyczny
city: Oswiecim
country: Poland
facility: Medicome Sp. z o.o.
city: Otwock
country: Poland
facility: Rodzinne Centrum Zdrowia
city: Plock
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Specjalistyczna Przychodnia Lekarska "MEDIKARD"
city: Tarnobrzeg
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Centrum Medyczne SBB
city: Warszawa
country: Poland
facility: Centrum Medyczne doktorA
city: Warszawa
country: Poland
facility: Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego
city: Warszawa
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej AURUM
city: Wroclaw
country: Poland
facility: Centrum Kardiologiczne Pro Corde Sp. z o.o. Niepubliczny Zaklad Opieki Zdrowotnej
city: Wroclaw
country: Poland
facility: Wro Medica
city: Chelyabinsk
country: Russian Federation
facility: City Clinical Hospital #6
city: Ekaterinburg
country: Russian Federation
facility: Ural State Medical University
city: Kemerovo
country: Russian Federation
facility: Federal Budget Healthcare Institution Medici - sanitary unit of Ministry of internal affairs of Russ
city: Kemerovo
country: Russian Federation
facility: Research Institute of Complex Cardiovascular Pathology
city: Krasnodar
country: Russian Federation
facility: Krasnodar Regional Clinical Hospital #2
city: Moscow
country: Russian Federation
facility: Moscow City State Budgetary Healthcare Institution City Clinical Hospital named after V.V. Veresayev
city: Moscow
country: Russian Federation
facility: Russian Cardiology Research and Production Center
city: Nizhniy Novgorod
country: Russian Federation
facility: City Hospital 13
city: Novosibirsk
country: Russian Federation
facility: State Budgetary Healthcare Institution of Novosibirsk Region City Clinical Hospital No. 19
city: Petrozavodsk
country: Russian Federation
facility: Republican Hospital n.a. V.A. Baranov
city: Rostov-on-Don
country: Russian Federation
facility: Municipal Budgetary Healthcare Institution City Emergency Hospital
city: Saint Petersburg
country: Russian Federation
facility: International Medical Center SOGAZ
city: Saint Petersburg
country: Russian Federation
facility: North-West State Medical University n.a. I.I. Mechnikov
city: Saint Petersburg
country: Russian Federation
facility: St Petersburg City Outpatient Clinic #109
city: Saratov
country: Russian Federation
facility: Saratov State Medical University
city: Saratov
country: Russian Federation
facility: State Healthcare Institution Regional Clinical Cardiologic Dispensary
city: Sochi
country: Russian Federation
facility: City Hospital #4
city: Tomsk
country: Russian Federation
facility: Research Cardiology Institute of Tomsk Scientific Center of RAMS Siberian Branch
city: Vladimir
country: Russian Federation
facility: State Budgetary Healthcare Institution of Vladimir Region City Hospital No. 4
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Clinical Hospital Centar Zvezdara
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa
city: Belgrade
country: Serbia
facility: Clinical Hospital Centre Zemun
city: Belgrade
country: Serbia
facility: Euromedik
city: Belgrade
country: Serbia
facility: Institute of Cardiovascular Diseases Dedinje
city: Belgrade
country: Serbia
facility: KBC Dr Dragisa Misovic Dedinje
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Niska Banja
country: Serbia
facility: Institute Niska Banja
city: Nis
country: Serbia
facility: Clinical Center Nis
city: Novi Sad
country: Serbia
facility: Clinical Centre of Vojvodina
city: Sremska Kamenica
country: Serbia
facility: Institute of Cardiovascular Diseases of Vojvodina
city: Uzice
country: Serbia
facility: General Hospital Uzice
city: Zajecar
country: Serbia
facility: Health Center Zajecar
city: Bardejov
country: Slovakia
facility: ALIAN, s.r.o
city: Bratislava
country: Slovakia
facility: CARDIOCONSULT, s.r.o.
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava
city: Dolny Kubin
country: Slovakia
facility: Kardio-Onkologia, s.r.o.
city: Kosice
country: Slovakia
facility: CARDIO D&R, s.r.o. Kosice
city: Kosice
country: Slovakia
facility: Zeleznicne zdravotnictvo Kosice, s.r.o.
city: Lucenec
country: Slovakia
facility: KARDIOMED s.r.o.
city: Moldava nad Bodvou
country: Slovakia
facility: MEDI M&M s.r.o.
city: Nove Mesto nad Vahom
country: Slovakia
facility: Nemocnica s poliklinikou Nove Mesto nad Vahom n.o.
city: Nove Zamky
country: Slovakia
facility: Cardioinvest s. r. o.
city: Roznava
country: Slovakia
facility: DIAB s.r.o.
city: Zilina
country: Slovakia
facility: MEDIVASA, s.r.o.
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: New Taipei City
country: Taiwan
facility: Mackay Memorial Hospital-Taipei branch
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan City
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: Cathay General Hospital
city: Taipei
country: Taiwan
facility: Chi Mei Medical Center
city: Taipei
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Medical Foundation Linkou Branch (Clinical Research Center)
Study officials:
affiliation: Imperial College London
name: Kausik Ray, MD
role: STUDY_CHAIR
References:
citation: Ray KK, Nicholls SJ, Buhr KA, Ginsberg HN, Johansson JO, Kalantar-Zadeh K, Kulikowski E, Toth PP, Wong N, Sweeney M, Schwartz GG; BETonMACE Investigators and Committees. Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes: A Randomized Clinical Trial. JAMA. 2020 Apr 28;323(16):1565-1573. doi: 10.1001/jama.2020.3308.
citation: Schwartz GG, Nicholls SJ, Toth PP, Sweeney M, Halliday C, Johansson JO, Wong NCW, Kulikowski E, Kalantar-Zadeh K, Ginsberg HN, Ray KK. Relation of insulin treatment for type 2 diabetes to the risk of major adverse cardiovascular events after acute coronary syndrome: an analysis of the BETonMACE randomized clinical trial. Cardiovasc Diabetol. 2021 Jun 22;20(1):125. doi: 10.1186/s12933-021-01311-9.
citation: Haarhaus M, Gilham D, Kulikowski E, Magnusson P, Kalantar-Zadeh K. Pharmacologic epigenetic modulators of alkaline phosphatase in chronic kidney disease. Curr Opin Nephrol Hypertens. 2020 Jan;29(1):4-15. doi: 10.1097/MNH.0000000000000570.
citation: Ray KK, Nicholls SJ, Ginsberg HD, Johansson JO, Kalantar-Zadeh K, Kulikowski E, Toth PP, Wong N, Cummings JL, Sweeney M, Schwartz GG. Effect of selective BET protein inhibitor apabetalone on cardiovascular outcomes in patients with acute coronary syndrome and diabetes: Rationale, design, and baseline characteristics of the BETonMACE trial. Am Heart J. 2019 Nov;217:72-83. doi: 10.1016/j.ahj.2019.08.001. Epub 2019 Aug 9.
citation: Gilham D, Tsujikawa LM, Sarsons CD, Halliday C, Wasiak S, Stotz SC, Jahagirdar R, Sweeney M, Johansson JO, Wong NCW, Kalantar-Zadeh K, Kulikowski E. Apabetalone downregulates factors and pathways associated with vascular calcification. Atherosclerosis. 2019 Jan;280:75-84. doi: 10.1016/j.atherosclerosis.2018.11.002. Epub 2018 Nov 14.