Clinical trial NCT00330369: DORADO - Fixed Doses of Darusentan as Compared to Placebo in Resistant Hypertension
Official title: DORADO - A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel Group Study to Evaluate the Efficacy and Safety of Fixed Doses of Darusentan in Subjects With Resistant Systolic Hypertension Receiving Combination Therapy With Three or More Antihypertensive Drugs, Including a Diuretic (Protocol DAR-311)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2006-05-26
Enrollment: 352
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a research study of a new experimental drug called darusentan. Darusentan is not currently approved by the U.S. Food and Drug Administration (FDA) for use in the United States, which means that a doctor cannot prescribe this drug. The purpose of this study is to determine if darusentan is effective in reducing systolic blood pressure in subjects with resistant systolic hypertension, despite treatment with full doses of three or more antihypertensive drugs, including a diuretic.


Eligibility criteria: Inclusion Criteria:

* Subjects who are competent to provide written consent
* Aged 35 to 80 years
* Subjects with diabetes and/or chronic kidney disease must have a mean systolic blood pressure ≥130 mmHg
* All other subjects must have a mean systolic blood pressure ≥140 mmHg
* Receiving and adhering to full doses of appropriate guideline-recommended antihypertensive drugs from three different classes of antihypertensive agents, including a diuretic
* Female subjects of non-childbearing potential (i.e., post-menopausal for at lest 2 years; surgically sterile)

Exclusion Criteria:

* Average sitting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg
* Serum ALT or AST \>2 x the upper limit of the normal range (ULN)
* Subjects who have experienced myocardial infarction, unstable angina pectoris, or a cerebrovascular accident (CVA) within 6 month; or sick sinus syndrome or second or third degree atrioventricular block, atrial fibrillation or recurrent atrial tachyarrhythmia, recurrent ventricular tachycardia, or symptomatic bradycardia
* Implanted pacemakers or implanted cardioverter defibrillator (ICD)
* Symptomatic congestive heart failure requiring treatment
* Hemodynamically significant valvular heart disease
* Type I diabetes mellitus
* Hemodialysis or peritoneal dialysis; or history of renal transplant
* Diagnosis or recurrence of malignancy within the past 3 years
* Sleep apnea, unless a recent sleep study demonstrates arterial oxygen saturation greater than or equal to 90%
* Subjects who perform alternating shift or night work
* Subjects who have participated in a clinical study involving another investigational drug or device within 4 weeks prior to Screening

Primary outcomes:
measure: Change from baseline in trough sitting systolic and diastolic blood pressure measured by sphygmomanometry
timeFrame: Baseline to Week 14
Secondary outcomes:
measure: Change from baseline in mean 24-hour systolic and diastolic ambulatory blood pressure
timeFrame: Baseline to Week 14
measure: Percentage of subjects to reach systolic blood pressure goal
timeFrame: Week 14
measure: Change from baseline in estimated glomerular filtration rate (eGFR)
timeFrame: Baseline to Week 14
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Hypertension Program
state: Alabama
city: Mobile
country: United States
facility: Comprehensive Heart Failure Center
state: Alabama
city: Tucson
country: United States
facility: Canyon Clinical Research
state: Arizona
city: Inglewood
country: United States
facility: Chrishard Medical Group
state: California
city: Los Angeles
country: United States
facility: VA Medical Center - WLA
state: California
city: Sacramento
country: United States
facility: Sacramento Heart and Vascular
state: California
city: Santa Ana
country: United States
facility: Apex Research Institute
state: California
city: Denver
country: United States
facility: Complete Renal Care
state: Colorado
city: Bridgeport
country: United States
facility: Connecticut Clinical Research, LLC
state: Connecticut
city: Washington
country: United States
facility: MedStar Diabetes Institute at Washington Hospital Center
state: District of Columbia
city: Deerfield Beach
country: United States
facility: Deerfield Beach Cardiology Associates
state: Florida
city: Fort Walton Beach
country: United States
facility: White-Wilson Medical Center
state: Florida
city: Gainsville
country: United States
facility: AMK Research
state: Florida
city: Hialeah
country: United States
facility: A.G.A. Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical
state: Florida
city: Jupiter
country: United States
facility: Ricardo A. Bedoya, Cardiology
state: Florida
city: Miami
country: United States
facility: International Research Association
state: Florida
city: Sarasota
country: United States
facility: Cardiovascular Center of Sarasota
state: Florida
city: Tampa
country: United States
facility: Tampa Bay Nephrology
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute, Inc.
state: Florida
city: Calhoun
country: United States
facility: Global Research Partners
state: Georgia
city: Honolulu
country: United States
facility: Kula Research
state: Hawaii
city: Elk Grove Village
country: United States
facility: Chicago Heart & Vein Clinic
state: Illinois
city: Evanston
country: United States
facility: Evanston Northwestern Healthcare
state: Illinois
city: Gurnee
country: United States
facility: Clinical Investigation Specialists, Inc.
state: Illinois
city: Lombard
country: United States
facility: Midwest Heart Foundation
state: Illinois
city: Marrero
country: United States
facility: American Clinical Research LLC
state: Louisiana
city: Slidell
country: United States
facility: Medical Research Institute
state: Louisiana
city: Auburn
country: United States
facility: Maine Research Associates
state: Maine
city: Scarborough
country: United States
facility: Cardiovascular Consultants of Maine
state: Maine
city: Baltimore
country: United States
facility: MODEL Clinical Research
state: Maryland
city: Oxon Hill
country: United States
facility: Maryland Medical Research/Og Medical Center
state: Maryland
city: Reisterstown
country: United States
facility: Clinical Associates
state: Maryland
city: Rockville
country: United States
facility: Rockville Internal Medicine Group
state: Maryland
city: Benzonia
country: United States
facility: Professional Clinical Research
state: Michigan
city: Flint
country: United States
facility: Nephrology and Hypertension / Hurley Medical Center
state: Michigan
city: Interlochen
country: United States
facility: Professional Clinical Research
state: Michigan
city: Pahrump
country: United States
facility: Specialty Medical Center
state: Nevada
city: Bronx
country: United States
facility: Bronx VA Medical Center / Mt. Sinai
state: New York
city: Greenville
country: United States
facility: Physicians East, PA
state: North Carolina
city: Cincinnati
country: United States
facility: The Lindner Clinical Trial Center
state: Ohio
city: Fairview Park
country: United States
facility: West Coast Cardiology Associates
state: Ohio
city: Oklahoma City
country: United States
facility: COR Clinical Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Southwest Cardiology Associates
state: Oklahoma
city: Oklahoma City
country: United States
facility: Sooner Clinical Research
state: Oklahoma
city: Tulsa
country: United States
facility: Castlerock Clinical Research Consultants
state: Oklahoma
city: Hillsboro
country: United States
facility: Hillsboro Cardiology, PC
state: Oregon
city: Allentown
country: United States
facility: Northeast Clinical Research Centers, Inc.
state: Pennsylvania
city: Camp Hill
country: United States
facility: Heritage Cardiology Associates
state: Pennsylvania
city: Downingtown
country: United States
facility: Brandywine Clinical Research
state: Pennsylvania
city: Lansdale
country: United States
facility: Green and Seidner Family Practice Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Providence
country: United States
facility: RI Hospital
state: Rhode Island
city: Columbia
country: United States
facility: Neem Research Group, Inc.
state: South Carolina
city: Desoto
country: United States
facility: Internal Medicine & Industrial Medicine
state: Texas
city: Ft Worth
country: United States
facility: T&R Clinical, P.A.
state: Texas
city: Lewisville
country: United States
facility: Pri-Med Care
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Midland
country: United States
facility: Diabetes Center of the Southwest
state: Texas
city: Plano
country: United States
facility: The Bracane Company
state: Texas
city: San Antonio
country: United States
facility: Innovative Clinical Trials
state: Texas
city: Burke
country: United States
facility: Burke Internal Medicine, Inc.
state: Virginia
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Gig Harbor
country: United States
facility: Peninsula Inernal Medicine
state: Washington
city: Tacoma
country: United States
facility: Liberty Research Center
state: Washington
city: Charleston
country: United States
facility: CAMC Clinical Trials Center
state: West Virginia
city: Buenos Aires
country: Argentina
facility: CIMEL
city: Buenos Aires
country: Argentina
facility: DIM (Clinica Privada)
city: Buenos Aires
country: Argentina
facility: Fundapres
city: Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital Jose Maria Ramos Meijia
city: Buenos Aires
country: Argentina
facility: Hospital Municipal bernardo Houssay
city: Buenos Aires
country: Argentina
facility: Medeos
city: Buenos Aires
country: Argentina
facility: Sanatorio Municipal Dr. Julio Mendez
city: Cordoba
country: Argentina
facility: Clinica Chutro SRL
city: Cordoba
country: Argentina
facility: Hospital San Roque
city: Belo Horizonte
country: Brazil
facility: Hospital Governador Israel Pinheiro
city: Belo Horizonte
country: Brazil
facility: Hospital Socor
city: Campinas
country: Brazil
facility: Centro Medico de Campinas
city: Curitiba
country: Brazil
facility: Hospital de Clinicas da Universidade Federal do Parana
city: Goiânia
country: Brazil
facility: Hospital das Clinicas
city: Maceió
country: Brazil
facility: Clinica de Exames
city: Sao Paulo
country: Brazil
facility: Centro Integrado Hospital do Rim e Hipertensao
city: Sao Paulo
country: Brazil
facility: Centro integrado hospital
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da USP
city: São José do Rio Preto
country: Brazil
facility: Instituto de Molestias
city: Cambridge
country: Canada
facility: Cambridge Cardiac Care Center
state: Ontario
city: Kitchener
country: Canada
facility: Clinical Research Solutions
state: Ontario
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: København
country: Denmark
facility: Bispebjerg Hospital
city: Dommartin les Toul
country: France
facility: CIC Hopital Jeanne D'Arc
city: Grenoble Cedex
country: France
facility: CHU de Grenoble
city: Marseille Cedex
country: France
facility: CHU la Timone Service de cardiologie
city: Roubaix
country: France
facility: CHU Victor Provo
city: Strasbourg Cedex
country: France
facility: Hôpital Civil, Service HTA maladies vasculaires
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik Forschungs GmbH
city: Berlin
country: Germany
facility: Charité Campus Buch
city: Cloppenburg
country: Germany
facility: St Josefs-Hospital
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Padua
country: Italy
facility: Azienda Ospedaliera University of Padua Policlinico
city: Barcelona
country: Spain
facility: Fundacio Puigvert
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Coruña
country: Spain
facility: Hospital Universitario de Santiago
city: Granada
country: Spain
facility: Hospital Clínico San Cecilio
city: Madrid
country: Spain
facility: Hospital Clínico de San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octobre
city: Malaga
country: Spain
facility: Hospital Carlos Haya
city: Stockholm
country: Sweden
facility: Cardiovascular Research, Karolinska Institue
city: Bolton,
country: United Kingdom
facility: Stonehill Medical Centre
city: Scotland
country: United Kingdom
facility: Townhead Surgery
city: Wiltshire
country: United Kingdom
facility: Avenue Surgery
city: Wiltshire
country: United Kingdom
facility: Hathaway Medical Centre
Study officials:
References:
citation: Weber MA, Black H, Bakris G, Krum H, Linas S, Weiss R, Linseman JV, Wiens BL, Warren MS, Lindholm LH. A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Oct 24;374(9699):1423-31. doi: 10.1016/S0140-6736(09)61500-2. Epub 2009 Sep 11.