EVEREST: Efficacy of Vasopressin Antagonism in hEart failuRE: Outcome Study With Tolvaptan

Congestive Heart Failure Clinical Trial

Official title:

Protocol 156-03-236: Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Long Term Efficacy and Safety of Oral Tolvaptan Tablets in Subjects Hospitalized With Worsening Congestive Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00071331
• Other study ID #: 156-03-236
• Status: Completed
• Phase: Phase 3
• First received: October 20, 2003
• Last updated: May 2, 2012
• Start date: September 2003
• Est. completion date: July 2006

Study information

• Verified date: May 2012
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the effectiveness of tolvaptan or placebo in adults with worsening congestive heart failure (CHF).

Description:

Study Design: Multicenter, randomized, double-blind, placebo-controlled

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3600
• Est. completion date: July 2006
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age greater than or equal to 18 years.

• Current hospitalization for chronic congestive heart failure with admission up to 48 hours prior to randomization. Chronic heart failure is defined as requiring treatment for a minimum of 30 days prior to hospitalization.

The subject must have signs of extracellular volume expansion, defined as two or more of the following: a) jugular venous distention; b) pitting edema (>1+); or c) dyspnea.

• NYHA Class III or IV at the time of hospitalization.

• Left Ventricular Ejection Fraction < = 40% within one year.

Exclusion Criteria

• Women who will not adhere to the reproductive precautions as outlined in the Informed Consent form.

• Positive urine pregnancy test.

• Inability to provide written informed consent.

• Cardiac surgery within 60 days of potential study enrollment, excluding percutaneous coronary interventions.

• Planned revascularization procedures, electrophysiologic (EP) device implantation, cardiac mechanical support implantation, cardiac transplantation, or other cardiac surgery within 30 days following study enrollment.

• Subjects who are on cardiac mechanical support.

• History of bi-ventricular pacer placement within the last 60 days.

• Co-morbid condition with an expected survival less than six months.

• Subjects with acute ST segment elevation myocardial infarction at the time of hospitalization.

• History of sustained ventricular tachycardia or ventricular fibrillation within 30 days, unless in the presence of an automatic implantable cardioverter defibrillator.

• History of a cerebrovascular accident within the last 30 days.

• Hemodynamically significant uncorrected primary cardiac valvular disease.

• Hypertrophic cardiomyopathy (obstructive or non-obstructive).

• CHF due to uncorrected thyroid disease, active myocarditis or known amyloid cardiomyopathy.

• Subjects with progressive or episodic neurological disease such as multiple sclerosis or history of multiple strokes.

• History of primary significant liver disease or acute hepatic failure, as defined by the investigator.

• History of poorly controlled diabetes mellitus.

• Morbid obesity, defined as > 159 kg (or 350 lbs) or BMI > 40.

• Supine systolic arterial blood pressure < 90 mmHg.

• Serum creatinine > 3.5 mg/dL or > 309.4 mmol/L.

• Serum potassium > 5.5 mEq/L or > 5.5 mmol/L.

• Hemoglobin < 9 g/dL or < 90 g/L.

• History of hypersensitivity and/or idiosyncratic reaction to benzazepine derivatives (such as benazapril).

• History of drug or medication abuse within the past year, or current alcohol abuse.

• Inability to take oral medications.

• Participation in another clinical drug or device trial within the past 30 days.

• Previous participation in this or any other tolvaptan clinical trial.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

Intervention

Drug:
• Tolvaptan

Locations

Country	Name	City	State
Argentina	Clinica Constituyentes de Moron	Buenos Aires
Argentina	Clinica Modelo de Moron	Buenos Aires
Argentina	Fundacion Favaloro	Buenos Aires
Argentina	Hospital Argerich	Buenos Aires
Argentina	Hospital Churruca	Buenos Aires
Argentina	Hospital Eva Peron	Buenos Aires
Argentina	Hospital Nacional Dr. Alejandro Posadas	Buenos Aires
Argentina	Hospital de Clinicas	Capital Federal
Argentina	Hospital Fernandez	Capital Federal
Argentina	Hospital Italiano de Buenos Aires	Capital Federal
Argentina	Hospital Privado Antartida	Capital Federal
Argentina	Hospital Ramos Mejia	Capital Federal
Argentina	Policlinica Bancaria	Capital Federal
Argentina	Sanatorio Municipal "Julio A. Mendez"	Capital Federal
Argentina	Hospital Allende	Cordoba
Argentina	Hospital Italiano de Cordoba	Cordoba
Argentina	Hospital Militar de Cordoba	Cordoba
Argentina	Hospital Privado Centro Medico de Cordoba	Cordoba
Argentina	Instituto de Cardiologia J. F. Cabral	Corrientes
Argentina	Hospital Central de San Isidro	San Isidro
Belgium	AZ Middelheim	Antwerpen
Belgium	AZ Imelda Ziekenhuis	Bonheiden
Belgium	Clinique St Elisabeth Place Louise	Namur
Belgium	Cliniques UCL Mont-Godinne	Yvoir
Brazil	Hospital Governador Israel Pinheiro	Belo Horizonte	MG
Brazil	Santa Casa de Misericordia de Belo Horizonte	Belo Horizonte	MG
Brazil	Hospital e Maternidade Celso Pierro	Campinas	SP
Brazil	Hospital Evangelico de Curitiba	Curitiba	PR
Brazil	Hospital Nossa Senhora das Gracas	Curitiba	PR
Brazil	Hospital das Clinicas da Universidade Federal de Goias	Goiania	GO
Brazil	Hospital Universitario Onofre Lopes	Natal
Brazil	Hospital das Clínicas de Porto Alegre	Porto Alegre
Brazil	Hospital das Clínicas de Porto Alegre	Porto Alegre	RS
Brazil	Hospital Mae de Deus	Porto Alegre	RS
Brazil	Hospital Nossa Senhora da Conceica	Porto Alegre	RS
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	RS
Brazil	Hospital Universitario Pedro Ernesto	Rio de Janeiro
Brazil	Santa Casa de Misericordia do Rio de Janeiro	Rio de Janeiro	RJ
Brazil	Fundacao Bahiana de Cardiologia- Hospital Universitario Professor Edgard Santos	Salvador	BA
Brazil	Hospital Santa Isabel da Santa Casa de Misericordia da Bahia	Salvador	BA
Brazil	Hospital de Base da Faculdade de Medicina de Sao Jose do Rio Preto	Sao Jose de Rio Preto	SP
Brazil	IMC- Instituto de Molestias Cardiovasculares	Sao Jose do Rio Preto	SP
Brazil	Instituto do Coracao do Hospital das Clinicas- Faculdade de Medicina da Universidade de Sao Paulo	Sao Paulo	SP
Canada	Brampton Research Associates	Brampton	Ontario
Canada	Peter Loougheed Center	Calgary	Alberta
Canada	Centre Hospitalier de l'Universite de Sherbrooke	Fleurimond	Quebec
Canada	CHRDL	Joliette	Quebec
Canada	Invascor Clinical Research	Longueuil	Quebec
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	Greater Niagara General Hospital	Niagara Falls	Ontario
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Hotel-Dieu de Saint-Jerome	Saint Jerome	Quebec
Canada	Cardiology Research Associates	Scarborough	Ontario
Canada	Scarborough Cardiology Research	Scarborough	Ontario
Canada	Health Sciences Center	St. John's	Newfoundland and Labrador
Canada	Surrey Memorial Hospital	Surrey	British Columbia
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	The Scarborough Hospital	Toronto	Ontario
Canada	University Health Network, Toronto Western Hospital	Toronto	Ontario
Canada	Victoria Heart Institute Foundation	Victoria	British Columbia
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
Czech Republic	I. interni kardio-angiologicka klinika LF MU	Brno
Czech Republic	Interni oddeleni	Jablonec nad Nisou
Czech Republic	Interni oddeleni	Nachod
Czech Republic	Interni klinika, Oddeleni Interna I, Kardiologie	Pardubice
Czech Republic	Interni oddeleni	Pisek
Czech Republic	I.Interni klinika	Plzen-Lochotin
Czech Republic	I.Interni oddeleni	Praha
Czech Republic	II.Interni klinika	Praha
Czech Republic	Kardiologicka klinika	Praha
Czech Republic	Kardiologicke oddeleni	Praha
Czech Republic	Klinika kardiologie	Praha
Czech Republic	Interni oddeleni	Usti nad Labem
Czech Republic	Interni klinika IPVZ	Zlin
France	Centre Hospitalier Regional d'Arras-Service de Cardiologie	Arras
France	Hopital General Henri Duffaut	Avignon
France	Centre Hospitalier Jeanne d'Arc	Bar-le-Duc
France	Hopital Louis Pradel	Bron cedex
France	Cabinet de Cardiologie et d'Explorations	Essey lès Nancy Cedex
France	Centre Hospitalier	Langres
France	CHU Montpellier	Montpellier
France	Centre Hospitalo-Universitaire de Nantes-Service de Cardiologie	Nantes Cedex
France	Hopital Pasteur	Nice
France	Centre Cardiologique du Nord	Saint Denis
France	Groupe Hospitalier Rangueil-Larrey CHU	Toulouse
France	Centre Hospitalier Universitaire de Nancy-Brabois	Vandoeuvre les Nancy
Germany	Klinikum Augsburg	Augsburg
Germany	Herzzentrum Bad Krozingen	Bad Krozingen
Germany	Herz- und Gefabklinik Bad Neustadt	Bad Neustadt-Saale
Germany	Vivantes Klinikum Neukoln	Berlin
Germany	Akademisches Lehrkrankenhaus d. HGS Essen	Essen
Germany	Universitatsklinik Essen	Essen
Germany	Georg-August-Universitat Gottingen	Gottingen
Germany	Universitatsklinikum der	Greifswald
Germany	Klinikum der Medizinischen Fakultat	Halle
Germany	Universitatsklinikum Eppendorf	Hamburg
Germany	Medizinische Universitätsklinik	Heidelberg
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	Universitatsklinikum des Saarland	Homburg/Saar
Germany	Friedrich Schiller Universitat Jena	Jena
Germany	Klinikum der Universitat zu Koln	Koln
Germany	University Leipzig	Leipzig
Germany	Universitatsklinikum Munster	Munster
Germany	Herz- und Diabetes Zentrum Nordrhein-Westfalen	Oeyenhausen
Germany	Universitat Regensburg	Regensburg
Germany	Marienkrankenhaus Soest	Soest
Germany	Robert-Bosch-Krankenhaus	Stuttgart
Italy	Ospedale Civile S. Giuseppe	Albano Laziale
Italy	Azienda Ospedaliera S. Michele	Cagliari
Italy	Ospedale Civile	Capri
Italy	Azienda USL n. 6 Ospedale Civile	Cecina
Italy	Poliambulatorio Valdichiana Ospedale di Cortona	Cortona
Italy	Centro Cardiologico Monzino	Milano
Italy	Ospedale Nigaurda Ca Granda	Milano
Italy	Fondazione Salvatore Maugeri	Montescano
Italy	Presidio Ospedaliero Villa Sofia	Palmero
Italy	Ospedali Riunti	Parma
Italy	IRCCS Policlinico S. Matteo	Pavia
Italy	IRCCS- Fondazione Salvatore Maugeri	Pavia
Italy	Ospedale S. Maria delle Grazie	Pozzuoli
Italy	Ospedale S. Bartolomeo	Sarzana
Italy	Ospedali Civile SS Annunziata	Sassari
Netherlands	Sint Lucas Andreas Ziekenhuis (loc. Lucas)	Amsterdam
Netherlands	Gelre Ziekenhuis (location Juliana)	Apeldoorn
Netherlands	Ziekenhuis Gooi Noord	Blaricum
Netherlands	Jeroen Bosch Ziekenhus (location Groot Ziekengasthius=GZG)	Den Bosch
Netherlands	Medisch Centrum Haaglanden (location Westeinde)	Den Haag
Netherlands	Deventer Ziekenhuis	Deventer
Netherlands	Ziekenhuis Gelderse Vallei	Ede
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Oosterschelde Ziekenhuizen	Goes
Netherlands	Martini Ziekenhuis (Loc. Martini Paviljoen)	Groningen
Netherlands	Spaarne Ziekenhuis	Heemstede
Netherlands	Ziekenhuis Hilversum	Hilversum
Netherlands	Canisius-Wilhelmina Ziekenhuis	Nijmegen
Netherlands	Isala Klinieken (Loc. Sophia)	Zwolle
Norway	Hjerte med. Avd. Haukeland Universitets Sykehus	Bergen
Norway	Nordlandsykehuset	Bodo
Norway	Hjertemed.avd. Akershus Universitetssykenhus	Nordbyhagen
Norway	Diakonhjemmets sykehus Oslo	Oslo
Norway	Med. Avd. Sykenhuset Telemark	Skien
Norway	Stavanger Helseforskning	Stavanger
Poland	Oddzial Kardiologii	Bydgoszcz
Poland	Oddzial Kardiologii	Krakow
Poland	Oddzial Kardiologii	Lodz
Poland	Oddzial Chorob Wewnetrznych	Olawa
Poland	Oddzial Kardiologiczny	Opole
Poland	Oddzial Kardiologii	Ostrowiec Swietokrzyski
Poland	Oddzial Kardiologiczny	Piotrków Trybunalski
Poland	Oddzial Kardiologiczny	Plock
Poland	Oddzial Kardiologii	Sieradz
Poland	Oddzial Kardiologii	Torun
Poland	Katedra i Oddzial Kliniczny Kardiologii Slaskiej Akademii	Tychy
Poland	I Klinika Choroby Wiencowej	Warszawa
Poland	Katedra i Klinika Chorab Wewnetrznych i Kardiologii	Warszawa
Poland	Oddzial Kardiologii	Wloclawek
Romania	Spitalul Judetean Brasov, Sectia de Cardiologie	Brasov
Romania	Institutul de Boli Cardiovasculare	Bucharest
Romania	Spitalul Caritas, Clinica Medicala	Bucharest
Romania	Spitalul de Urgenta Floreasca, Clinica de Cardiologie	Bucharest
Romania	Spitalul Universitar de Urgenta Bucuresti	Bucharest
Romania	Spitalul Universitar de Urgenta	Bucuresti
Romania	Institutul Inimii, Prof.N. Stancioiu	Cluj-Napoca
Romania	Centrul de Cardiologie Craiova	Craiova
Romania	Spitalul Clinic Universitar ,,Sf. Spiridon"	Iasi
Romania	Spitalul Clinic Judetean Mures	Targu-Mures
Romania	Institutul de Boli Cardiovasculare Timisoara	Timisoara
Russian Federation	Botkins Moscow City Hospital	Moscow
Russian Federation	Burdenko Main Military Clinical Hospital	Moscow
Russian Federation	Cardiology Research Center	Moscow
Russian Federation	Central Clinical Hospital Presidential	Moscow
Russian Federation	City Clinical Hospital 2	Moscow
Russian Federation	Institute of Physico-Chemical Medicine	Moscow
Russian Federation	Medical Center of General Management	Moscow
Russian Federation	Moscow Medical Academy	Moscow
Russian Federation	Moscow Regional Research Clinical Institute n.a. Vishnevsky	Moscow
Russian Federation	Moscow State University of Medicine and Dentistry	Moscow
Russian Federation	Moscow State University of Medicine and Dentistry - City Hospital #11	Moscow
Russian Federation	Moscow State University of Medicine and Dentistry - City Hospital #40	Moscow
Russian Federation	Russian State Medical University	Moscow
Russian Federation	Veterans Hospital #3	Moscow
Russian Federation	Cardiology Research Institute of the Ministry of Health of the Russian Federation	St. Petersburg
Russian Federation	City Alexandrovsky Hospital, ICU Department	St. Petersburg
Russian Federation	City Hospital #31	St. Petersburg
Russian Federation	City Hospital 8	St. Petersburg
Russian Federation	Military Medical Academy	St. Petersburg
Russian Federation	St. Elisabeth City Hospital	St. Petersburg
Russian Federation	St. Petersburg Clinical Hospital of Russian Academy of Sciences	St. Petersburg
Russian Federation	St. Petersburg Dzanelidze State Scientific Research Institute for Emergency Medical Care	St. Petersburg
Russian Federation	St. Petersburg Medical Postgraduate Academy	St. Petersburg
Russian Federation	St. Petersburg State University	St. Petersburg
Spain	Hospital de Torrecardenas	Almeria
Spain	Hospital Clinic y Provincial	Barcelona
Spain	Hospital de Cruces	Bilbao
Spain	Hospital Reina Sofia, in Cordoba	Cordoba
Spain	Hospital Doce de Octubre	Madrid
Spain	Hospital Severo Ochoa	Madrid
Spain	Hospital Universitari de Tarragona Joan XXIII	Tarragona
Spain	Hospital General Universitario de Valencia	Valencia
Sweden	Medicinkliniken	Goteborg
Sweden	Avd. for intermedicin	Gothenburg
Sweden	Kardiologkliniken	Linkoping
Sweden	Kardiologkliniken	Malmo
Sweden	Forskiningsenheten,	Molndal
Sweden	Enheten for internmedicin, Karolinska Institutet	Stockholm
Sweden	Hjartkliniken, M84	Stockholm
Sweden	Kardiologkliniken	Stockholm
Sweden	Hjartcentrum,	Umea
Sweden	Cardiologkliniken, Avd 50F	Uppsala
Switzerland	Cardiocentro Ticino	Lugano
United Kingdom	Bradford Royal Infirmary	Bradford
United Kingdom	Castle Hill Hospital	Cottingham
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	Northern Manchester General Hospital	Manchester
United Kingdom	Scunthorpe General Hospital	Scunthorpe
United States	Akron General Medical Center	Akron	Ohio
United States	Albany Associates in Cardiology	Albany	New York
United States	Asheville Cardiology Associates	Asheville	North Carolina
United States	Atlanta Heart and Vascular Research Group	Atlanta	Georgia
United States	Cardiac Disease Specialists PC	Atlanta	Georgia
United States	Florida Cardiovascular Research	Atlantis	Florida
United States	Androscoggin Cardiology Associates	Auburn	Maine
United States	Austin Cardiovascular Associates	Austin	Texas
United States	Primary Care Cardiology Research	Ayer	Massachusetts
United States	Bakersfield Memorial Hospital	Bakersfield	California
United States	Central Cardiology Medical Center	Bakersfield	California
United States	MidAtlantic Cardiovascular Associates	Baltimore	Maryland
United States	Midatlantic Cardiovascular Associates	Baltimore	Maryland
United States	MidAtlantic Cardiovascular Associates	Baltimore	Maryland
United States	Northeast Cardiology Associates	Bangor	Maine
United States	North Shore Cardiologists	Bannockburn	Illinois
United States	Southeast Texas Cardiology Associates	Beaumont	Texas
United States	Midatlantic Cardiovascular Associates	Bel Air	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Idaho Cardiology Associates	Boise	Idaho
United States	Beth Israel Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Alamance Regional Medical Center	Burlington	North Carolina
United States	Clinical Research Limited	Canton	Ohio
United States	The Louisiana Heart Center	Chalmette	Louisiana
United States	University of North Carolina	Chapel Hill	North Carolina
United States	CAMC Clinical Trials	Charleston	West Virginia
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ralph H. Johnson VAMC	Charleston	South Carolina
United States	Mid Carolina Cardiology	Charlotte	North Carolina
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	The Chattanooga Heart Institute	Chattanooga	Tennessee
United States	Northwestern University	Chicago	Illinois
United States	Sterling Research Group	Cincinnati	Ohio
United States	The Lindner Clinical Trial Center	Cincinnati	Ohio
United States	Missouri Cardiovascular Specialists	Columbia	Missouri
United States	South Carolina Heart Center	Columbia	South Carolina
United States	Midwest Cardiology Research Foundation	Columbus	Ohio
United States	Georgia Heart Specialists	Covington	Georgia
United States	Northshore Medical Research	Covington	Louisiana
United States	Cardiopulmonary Research Science and Technology Institute	Dallas	Texas
United States	The Dayton Heart Center	Dayton	Ohio
United States	Aurora Denver Cardiology Associates	Denver	Colorado
United States	University of Colorado	Denver	Colorado
United States	John Dingell VA Medical Center	Detroit	Michigan
United States	Duke Cardiology Research	Durham	North Carolina
United States	Durham VA Medical Center	Durham	North Carolina
United States	Shore Health System	Easton	Maryland
United States	Wisconsin Center For Clinical Research	Elkhorn	Wisconsin
United States	The Cardiovascular Group PC	Fairfax	Virginia
United States	Cleveland Cardiovascular Research	Fairview Park	Ohio
United States	Inova Institute of Research	Falls Church	Virginia
United States	Heart and Vascular Clinic of North Colorado	Fort Collins	Colorado
United States	Cardiology Associates of Fort Lauderdale	Fort Lauderdale	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Phoenix Memorial Hospital	Gilbert	Arizona
United States	Pitt County Memorial Hospital, The Heart Center	Greenville	North Carolina
United States	Hendersonville Cardiology	Hendersonville	North Carolina
United States	Leonard J Chabert Medical Center	Houma	Louisiana
United States	The Heart Center	Huntsville	Alabama
United States	The Care Group	Indianapolis	Indiana
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Jacksonville Heart Center	Jacksonville	Florida
United States	Jacksonville Heart Center	Jacksonville Beach	Florida
United States	Cardiology Associates, P.C.	Johnson City	New York
United States	Mid America Cardiology	Kansas City	Kansas
United States	VA Medical Center- Kansas City	Kansas City	Missouri
United States	Cardiovascular Associates	Kingsport	Tennessee
United States	Cardiology Associates	Larkspur	California
United States	Bryan LGH Heart Institute	Lincoln	Nebraska
United States	Central Arkansas Veterans Healthcare Systems	Little Rock	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Midwest Heart Research Found.	Lombard	Illinois
United States	North Ohio Research Limited	Lorain	Ohio
United States	LAC/USC Medical Center	Los Angeles	California
United States	VA Medical Center- W. Los Angeles	Los Angeles	California
United States	Cardiovascular Associates	Louisville	Kentucky
United States	Louisville Cardiology Medical Group	Louisville	Kentucky
United States	Cardiology Associates Covenant Medical Group	Lubbock	Texas
United States	New England Heart Institute	Manchester	New Hampshire
United States	North Shore University Hospital	Manhasset	New York
United States	McAllen Heart Clinic	McAllen	Texas
United States	Melbourne Internal Medicine Assoc.	Melbourne	Florida
United States	Baptist Clinical Research Center	Memphis	Tennessee
United States	Stern Cardiovascular Center	Memphis	Tennessee
United States	Idaho Cardiology Associates	Meridian	Idaho
United States	Miami Research and Education Foundation	Miami	Florida
United States	University of Miami/ Jackson Memorial Hospital	Miami	Florida
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Minneapolis Heart Institute	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	Mission Internal Medical Group	Mission Viejo	California
United States	The Heart Group	Mobile	Alabama
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Vanderbilt Clinical Trials Center	Nashville	Tennessee
United States	New York Presbyterian Hospital	New York	New York
United States	St. Lukes-Roosevelt Hospital Centers	New York	New York
United States	St. Vincents Hospital and Medical Center	New York	New York
United States	Christiana Care Health System	Newark	Delaware
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	University of Medicine and Dentistry of New Jersey	Newark	New Jersey
United States	Illinois Heart & Lung Associates	Normal	Illinois
United States	Bakus Resesarch	Norwich	Connecticut
United States	Ocala Resarch Institute	Ocala	Florida
United States	Integris Heart Research Center	Oklahoma City	Oklahoma
United States	Oklahoma Cardiovascular Research Group	Oklahoma City	Oklahoma
United States	Heart Consultants	Omaha	Nebraska
United States	Cardiology Research Associates	Ormond Beach	Florida
United States	Garden State Cardiology	Paramus	New Jersey
United States	Heart Care Midwest	Peoria	Illinois
United States	Nisus Research	Petoskey	Michigan
United States	Cardiology Consultants of Philadelphia	Philadelphia	Pennsylvania
United States	Arizona Heart Institute	Phoenix	Arizona
United States	The Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Charlotte Heart Group Research Center	Port Charlotte	Florida
United States	Maine Medical Center	Portland	Maine
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	ARI Clinical Trials	Redondo Beach	California
United States	Cardiovascular Associates of Virginia	Richmond	Virginia
United States	Medical College of Virginia	Richmond	Virginia
United States	Roanoke Heart Institute	Roanoke	Virginia
United States	Mayo Clinic, Division of Cardiology	Rochester	Minnesota
United States	St. Francis Hospital	Roslyn	New York
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Covenant Medical Center	Saginaw	Michigan
United States	VA Salt Lake City Health Care System	Salt Lake City	Utah
United States	University of Texas Health Science Center	San Antonio	Texas
United States	Wilford Hall Medical Center,	San Antonio	Texas
United States	San Diego Cardiac Center	San Diego	California
United States	North Ohio Research Limited	Sandusky	Ohio
United States	Pacific Heart Institute	Santa Monica	California
United States	Cardiovascular Center of Sarasota	Sarasota	Florida
United States	Guthrie Clinic, LTD	Sayre	Pennsylvania
United States	Buxmont Cardiology Associates, PC	Sellersville	Pennsylvania
United States	Cardiac Centers of LA, LLC	Shreveport	Louisiana
United States	Lousiana State University Health Sciences Center	Shreveport	Louisiana
United States	Empire Health Services	Spokane	Washington
United States	Rockwood Clinic	Spokane	Washington
United States	St. Louis University	St. Louis	Missouri
United States	Park Nicollet Heart Center	St. Louis Park	Minnesota
United States	Regions Hospital Cardiology Research	St. Paul	Minnesota
United States	St. Paul Heart Clinic	St. Paul	Minnesota
United States	The Heart and Vascular Institute of Florida	St. Petersburg	Florida
United States	SUNY	Syracuse	New York
United States	Scott & White Clinic Division of Cardiology	Temple	Texas
United States	Northwest Ohio Cardiology Consultants	Toledo	Ohio
United States	Heart Associates, P.A.	Towson	Maryland
United States	MidAtlantic Cardiovascular Associates	Towson	Maryland
United States	Beaumont Hospital	Troy	Michigan
United States	Saguaro Clinical Research	Tucson	Arizona
United States	The Cardiology Group	Tullahoma	Tennessee
United States	Cardiology Associates of North Mississippi	Tupelo	Mississippi
United States	Cardiovascular Consultants Medical Group, Inc.	Walnut Creek	California
United States	VA Medical Center	Washington	District of Columbia
United States	South Bay Cardiovascular Associates	West Islip	New York
United States	Cardiology Associates of West Reading	West Reading	Pennsylvania
United States	MidAtlantic Cardiovascular Associates	Westminster	Maryland
United States	Buffalo Cardiology and Pulmonary Associates	Williamsville	New York
United States	Michigan Heart	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Czech Republic,  France,  Germany,  Italy,  Netherlands,  Norway,  Poland,  Romania,  Russian Federation,  Spain,  Sweden,  Switzerland,  United Kingdom,