Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD (BETonMACE)
Diabetes Mellitus, Type 2, Coronary Artery Disease
About this trial
This is an interventional prevention trial for Diabetes Mellitus, Type 2
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
Sites / Locations
- Instituto de Investigaciones Clinicas Bahia Blanca
- Bioclinica Buenos Aires
- Centro Privado de Enfermedades Cardiovasculares
- Consultorios Asociados Endocronología E Investigación Clínica Aplicada
- Instituto Cardiovascular de Buenos Aires
- Sanatorio Guemes
- Clinica Coronel Suarez
- Instituto de Cardiologia de Corrientes Juana Francisca Cabral
- CEMAIC
- Centro Médico Colón
- Centro Médico Luquez
- Clínica Privada Del Prado Sociedad de Responsabilidad Limitada
- Fundación Clínica Colombo
- Hospital Cordoba
- Hospital San Roque
- Instituto Del Corazón
- Instituto Modelo de Cardiologia
- Instituto Médico DAMIC
- Ipac Caraffa
- Sanatorio Allende
- Centro Médico Libertad
- CIMEL
- Instituto de Investigaciones Clínicas Mar Del Plata
- Hospital Central
- DIM Clinica Privada
- Instituto de Hematologia Y Medicina Clinica
- Sanatorio Britanico de Rosario
- Prevencion Cardio Vascular
- Grupo Medico Alem
- Bioclinica Tucumán
- Centro Modelo de Cardiologia
- Investigaciones Clinicas Tucuman
- Centro de Investigaciones Clínicas Del Litoral SRL
- Sanatorio San Francisco
- Clínica FUSAVIM Privada
- Instituto de Investigaciones Clínicas Zárate
- Flinders Medical Centre
- ZNA Middelheim
- Imelda VZW
- AZ Turnhout
- Multiprofile Hospital For Active Treatment Dr Tota Venkova
- Multiprofile Hospital for Active Treatment - Prof. Dr. Paraskev Stoyanov AD
- Multiprofile Hospital For Active Treatment - Pazardzhik AD
- University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski EAD
- Multiprofile Hospital For Active Treatment - Dr. Bratan Shukerov AD
- Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda
- City Clinic University Multiprofile Hospital for Active Treatment EOOD
- Medical Center Kardiohelp EOOD
- Second Multiprofile Hospital for Active Treatment Sofia
- Synexus Affiliate - Diagnostic and Consulting Center Ascendent
- University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
- University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD
- Medical Center Orfey OOD
- Multiprofile Hospital for Active Treatment Sveta Marina EAD
- General Hospital Karlovac
- Special Hospital for medicinal rehabilitation Krapinske Toplice
- Clinical Hospital Osijek
- General Hospital Dr Josip Bencevic
- General Hospital Virovitica
- Clinical Hospital Sveti duh
- DRK Kliniken Berlin Westend
- Medizinisches Versorgungszentrum am Küchwald GmbH
- Zentrum für Klinische Prüfung in der Facharztzentrum Dresden Neustadt Gbr
- Katholisches Krankenhaus St. Johann Nepomuk
- Heidelberger Praxisklinik für Kardiologie
- Klinikum Hoyerswerda
- Studienzentrum Dr.Appel
- Asklepios Klinik Langen
- Klinikum Leverkusen GmbH
- Bajai Szent Rókus Kórház
- Grof Tisza Istvan Korhaz Berettyoujfalu
- Bajcsy-Zsilinszky Korhaz es Rendelointezet
- Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet
- Gottsegen Gyorgy Orszagos Kardiologiai Intezet
- Magyar Honvédség Egészségügyi Központ
- Semmelweis Egyetem
- Synexus (DRS) - Synexus Magyarország Kft. Budapest
- Szent Margit Korhaz
- Szent Rókus Kórház és Intézményei
- Selye János Kórház
- TaNaMed Kft.
- Kanizsai Dorottya Kórház
- Coromed-SMO Kft.
- Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
- Tolna Megyei Balassa János Kórház
- Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
- Barzilai Medical Center
- Soroka University Medical Centre
- Hillel Yaffe Medical Center
- Bnei Zion Medical Center
- Lady Davis Carmel Medical Center
- Linn Medical Center Clalit Health Services
- Rambam Medical Center
- Edith Wolfson Medical Center
- Hadassah University Hospital Ein Kerem
- Hadassah University Hospital Mount Scopus
- Shaare Zedek Medical Center
- Meir Medical Center
- Galilee Medical Center
- Nazareth EMMS Hospital
- Chaim Sheba Medical Center
- Kaplan Medical Center
- ZIV Medical Center
- Clalit Health Medical Center
- Tel Aviv Sourasky Medical Center
- Baruch Padeh Poriya Medical Center
- Fundacion Cardiovascular de Aguascalientes AC
- Hospital Cardiológica Aguascalientes
- Investigacion en Salud y Metabolismo S.C.
- Centro de Investigación Biomedica y Farmaceutica
- Clinica Integral del Paciente Diabetico y Obeso
- Fundación de Atención e Investigación Médica Lindavista S.C.
- Centro Para el Desarrollo de la Medicina y de Asistencia Especializada SC
- Centro de Investigacion y Atencion de Diabetes, Endocrinologia y Nutricion
- Arechavaleta Granell Maria del Rosario
- Centro de Investigacion Medica Biologica Y de Terapia Avanzada SC
- Unidad de Investigacion Clinica Cardiometabolica de Occidente SC
- Hospital Angeles Leon
- Centro de Desarrollo Biomédico
- Sanatorio y Servicios Médicos Obregón S.A. de C.V.
- Instituto Cardiovascular de Monclova
- Hospital Universitario Dr. Jose Eleuterio González
- IMED Internal Medicine Clin Trials
- Unidad de Investigación Clínica En Medicina SC
- Diabetes Total, S.A de C.V.
- Investigacion Biomedica Aplicada de Hidalgo S.A. de C.V.
- Cardioarritmias e Investigación S.C.
- Hospital Central Dr Ignacio Morones Prieto
- INBIOMEDYC Toluca
- Centro de Alta Especialidad Dr. Rafael Lucio
- Dr. Humberto Alvarez Lopez
- Meander Medisch Centrum
- OLVG locatie Oost
- VU Medisch Centrum
- Podlaski Osrodek Kardiologii Poradnia Prywatna
- Malopolskie Centrum Sercowo-Naczyniowe
- Polsko-Amerykanskie Kliniki Serca
- Gabinet Kardiologiczno-Internistyczny
- Niepubliczny Zaklad Opieki Zdrowotnej Centrum Uslug Medycznych Promont-Med.
- Diamond Clinic
- Szpital Specjalistyczny im. Jozefa Dietla w Krakowie
- Zespol Przychodni Specjalistycznych DIAB-END-COR Sp. z o.o.
- Prywatna Praktyka Lekarska MAZ-MEDICA Maciej R.Mazurkiewicz
- Uniwersytecki Szpital Kliniczny im. Wojskowej Akademii Medycznej Centralny Szpital Weteranow
- Polsko-Amerykanskie Kliniki Serca
- Pro Corde, Dom Medyczny
- Medicome Sp. z o.o.
- Rodzinne Centrum Zdrowia
- Niepubliczny Zaklad Opieki Zdrowotnej Specjalistyczna Przychodnia Lekarska "MEDIKARD"
- Niepubliczny Zaklad Opieki Zdrowotnej Centrum Medyczne SBB
- Centrum Medyczne doktorA
- Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego
- Niepubliczny Zaklad Opieki Zdrowotnej AURUM
- Centrum Kardiologiczne Pro Corde Sp. z o.o. Niepubliczny Zaklad Opieki Zdrowotnej
- Wro Medica
- City Clinical Hospital #6
- Ural State Medical University
- Federal Budget Healthcare Institution Medici - sanitary unit of Ministry of internal affairs of Russ
- Research Institute of Complex Cardiovascular Pathology
- Krasnodar Regional Clinical Hospital #2
- Moscow City State Budgetary Healthcare Institution City Clinical Hospital named after V.V. Veresayev
- Russian Cardiology Research and Production Center
- City Hospital 13
- State Budgetary Healthcare Institution of Novosibirsk Region City Clinical Hospital No. 19
- Republican Hospital n.a. V.A. Baranov
- Municipal Budgetary Healthcare Institution City Emergency Hospital
- International Medical Center SOGAZ
- North-West State Medical University n.a. I.I. Mechnikov
- St Petersburg City Outpatient Clinic #109
- Saratov State Medical University
- State Healthcare Institution Regional Clinical Cardiologic Dispensary
- City Hospital #4
- Research Cardiology Institute of Tomsk Scientific Center of RAMS Siberian Branch
- State Budgetary Healthcare Institution of Vladimir Region City Hospital No. 4
- Clinical Center of Serbia
- Clinical Hospital Centar Zvezdara
- Clinical Hospital Center Bezanijska Kosa
- Clinical Hospital Centre Zemun
- Euromedik
- Institute of Cardiovascular Diseases Dedinje
- KBC Dr Dragisa Misovic Dedinje
- Military Medical Academy
- Clinical Center Kragujevac
- Institute Niska Banja
- Clinical Center Nis
- Clinical Centre of Vojvodina
- Institute of Cardiovascular Diseases of Vojvodina
- General Hospital Uzice
- Health Center Zajecar
- ALIAN, s.r.o
- CARDIOCONSULT, s.r.o.
- Univerzitna nemocnica Bratislava
- Kardio-Onkologia, s.r.o.
- CARDIO D&R, s.r.o. Kosice
- Zeleznicne zdravotnictvo Kosice, s.r.o.
- KARDIOMED s.r.o.
- MEDI M&M s.r.o.
- Nemocnica s poliklinikou Nove Mesto nad Vahom n.o.
- Cardioinvest s. r. o.
- DIAB s.r.o.
- MEDIVASA, s.r.o.
- Changhua Christian Hospital
- Kaohsiung Chang Gung Memorial Hospital
- Kaohsiung Veterans General Hospital
- Mackay Memorial Hospital-Taipei branch
- China Medical University Hospital
- National Cheng Kung University Hospital
- Tri-Service General Hospital
- Cathay General Hospital
- Chi Mei Medical Center
- Far Eastern Memorial Hospital
- National Taiwan University Hospital
- Taipei Veterans General Hospital
- Chang Gung Medical Foundation Linkou Branch (Clinical Research Center)
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
High-Intensity statin therapy+RVX000222
High-Intensity statin therapy+Placebo
Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)
Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)