Clinical trial NCT00389779: DORADO-AC - Optimized Doses of Darusentan as Compared to an Active Control in Resistant Hypertension
Official title: A Phase 3 Randomized, Double-Blind, Placebo- and Active-Controlled, Multi-center, Parallel Group Study to Evaluate the Safety and Efficacy of Darusentan in Subjects With Resistant Hypertension Receiving Combination Therapy With Three or More Antihypertensive Drugs, Including a Diuretic, as Compared to Guanfacine or Placebo (Protocol DAR-312)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2006-10-19
Enrollment: 849
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 randomized, double-blind, placebo- and active-controlled study of a new experimental drug called darusentan. Darusentan is not currently approved by the United States Food and Drug Administration (FDA), which means that a doctor cannot prescribe this drug. The purpose of this study is to determine if darusentan is effective in reducing systolic and diastolic hypertension despite treatment with full doses of three or more antihypertensive drugs, including a diuretic. Subjects will be randomized to darusentan (optimized dose), an active comparator, or placebo, administered orally. The treatment period for this trial is 14 weeks.


Eligibility criteria: SELECTED INCLUSION CRITERIA:

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

SELECTED EXCLUSION CRITERIA:

1. Average sitting systolic and diastolic blood pressure greater than or equal to 180 mmHg and 110 mmHg, respectively;
2. Subjects treated with a central alpha-2 agonist and/or imidazoline receptor agonist;
3. Left ventricular dysfunction;
4. Serum ALT or AST greater than 2 times the Upper Limit of Normal;
5. Subjects who have experienced myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 6 months; or sick sinus syndrome or second or third degree atrioventricular block, atrial fibrillation or recurrent atrial tachycardia, recurrent ventricular tachycardia, or symptomatic bradycardia;
6. Implanted pacemakers or cardioverter defibrillator;
7. Symptomatic congestive heart failure requiring treatment;
8. Hemodynamically significant valvular heart disease;
9. Hemodialysis or peritoneal dialysis, or history of renal transplant;
10. Type I diabetes mellitus;
11. Diagnosis or recurrence of malignancy within the past 3 years;
12. Sleep apnea, unless a recent sleep study demonstrated arterial oxygenation saturation greater than or equal to 90%, treated or untreated;
13. Subjects who perform alternating shift or night work;
14. 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: Percentage of subjects reaching systolic blood pressure goal after 14 weeks of treatment
timeFrame: Week 14
measure: Change from baseline in mean 24-hour systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring (ABPM)
timeFrame: Baseline to 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: Alabama Internal Medicine, PC
state: Alabama
city: Birmingham
country: United States
facility: Greystone Medical Research, LLC
state: Alabama
city: Huntsville
country: United States
facility: The Heart Center, PC
state: Alabama
city: Montgomery
country: United States
facility: Mulberry Medical Associates, PC
state: Alabama
city: Glendale
country: United States
facility: Arizona Center for Clinical Research
state: Arizona
city: Glendale
country: United States
facility: Cardiovascular Consultants, Ltd.
state: Arizona
city: Phoenix
country: United States
facility: Lovelace Scientific Resources, Inc
state: Arizona
city: Sierra Vista
country: United States
facility: Cochise Clinical Research
state: Arizona
city: Tucson
country: United States
facility: Southwest Heart
state: Arizona
city: Hot Springs
country: United States
facility: HealthFirst Physician of AR, PA dba Convenient Care Clinic
state: Arkansas
city: Jonesboro
country: United States
facility: NEA Clinic
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Primary Care Clinic, PA
state: Arkansas
city: Little Rock
country: United States
facility: Medical Investigations Inc.
state: Arkansas
city: Bakersfield
country: United States
facility: Highgrove Medical Center
state: California
city: Bakersfield
country: United States
facility: Central Cardiology Medical Clinic
state: California
city: Beverly Hills
country: United States
facility: Impact Clinical Trials
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Rancho Cucamonga
country: United States
facility: Rancho Cucamonga Clinical Trials
state: California
city: Santa Monica
country: United States
facility: Pacific Heart Institute
state: California
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: Aurora Denver Cardiology Associates
state: Colorado
city: Aurora
country: United States
facility: Aurora Denver Cardiology Associates
state: Colorado
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Defuniak Springs
country: United States
facility: Doctors Medical Center of Walton County
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Ft. Lauderdale
country: United States
facility: Maxine Hamilton, MD, PA
state: Florida
city: Jacksonville
country: United States
facility: St. John's Center for Clinical Research
state: Florida
city: Largo
country: United States
facility: Private Practice of Dr. Bridget Bellingar
state: Florida
city: Miami
country: United States
facility: A+ Research Inc.
state: Florida
city: Miami
country: United States
facility: AppleMed Research, Inc.
state: Florida
city: N. Miami Beach
country: United States
facility: Internal Medicine Associates of South Florida
state: Florida
city: Ormond Beach
country: United States
facility: Ormond Medical Arts Pharmaceutical Research center
state: Florida
city: Pensacola
country: United States
facility: Northwest Florida Heart Group, PA - Research Dept
state: Florida
city: Sarasota
country: United States
facility: Cardiovascular Center of Sarasota
state: Florida
city: St. Petersburg
country: United States
facility: Suncoast Cardiovascular Research, Inc.
state: Florida
city: Tampa
country: United States
facility: Tampa Bay Nephrology Associates, PL
state: Florida
city: Tampa
country: United States
facility: Orlando Rangel, MD, PA
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Bogart
country: United States
facility: AMR Research Associates, LLC
state: Georgia
city: Tucker
country: United States
facility: Atlanta Vascular Research Foundation
state: Georgia
city: Bannockburn
country: United States
facility: North Shore Cardiologist
state: Illinois
city: Melrose Park
country: United States
facility: Consultants in Cardiovascular Med (CIS)
state: Illinois
city: Normal
country: United States
facility: Illinois Heart & Lunch Research
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center-Heart, Lung & Vascular Institute
state: Illinois
city: Muncie
country: United States
facility: Medical Consultants, PC
state: Indiana
city: Louisville
country: United States
facility: University Medical Associates
state: Kentucky
city: Lafayette
country: United States
facility: Dr. Jeffrey Chen
state: Louisiana
city: New Orleans
country: United States
facility: Louisiana Research Associates, Inc
state: Louisiana
city: Auburn
country: United States
facility: Maine Research Associate
state: Maine
city: Biddeford
country: United States
facility: PrimeCare Internal Medicine
state: Maine
city: Alpena
country: United States
facility: Great Lakes Heart Center of Alpena
state: Michigan
city: Petoskey
country: United States
facility: Internal Medicine of Nothern Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis VAMC
state: Minnesota
city: St. Cloud
country: United States
facility: Central Minnesota Heart Center at St. Cloud Hospital
state: Minnesota
city: St. Paul
country: United States
facility: St. Paul Cardiology
state: Minnesota
city: Kalispell
country: United States
facility: Glacier View Cardiology, PC
state: Montana
city: Las Vegas
country: United States
facility: Impact Clinical Trials
state: Nevada
city: Linden
country: United States
facility: NJ Heart
state: New Jersey
city: Passaic
country: United States
facility: New Jersey Physicians
state: New Jersey
city: Brooklyn
country: United States
facility: Lifeline Research Institute
state: New York
city: Charlotte
country: United States
facility: Metrolina Internal Medicine, PA
state: North Carolina
city: Charlotte
country: United States
facility: Heart Care Center of Charlotte
state: North Carolina
city: Winterville
country: United States
facility: Physicians East, PA
state: North Carolina
city: Oklahoma City
country: United States
facility: Plaza Medical Group, PC
state: Oklahoma
city: Tulsa
country: United States
facility: Castlerock Clinical Research Counsultants, LLC
state: Oklahoma
city: Ashland
country: United States
facility: Integrated Medical Research PC
state: Oregon
city: Pawtucket
country: United States
facility: Blackstone Cardiology Associates
state: Rhode Island
city: Charleston
country: United States
facility: Charleston Cardiology
state: South Carolina
city: Greenville
country: United States
facility: Paris View Family Practice
state: South Carolina
city: Greer
country: United States
facility: Internal Medicine of Greer
state: South Carolina
city: Cleveland
country: United States
facility: Scenic City Research
state: Tennessee
city: Beaumont
country: United States
facility: Southeast Texas Clinical Research Center
state: Texas
city: Dallas
country: United States
facility: Cardiovascular Research Inst. of Dallas
state: Texas
city: Dallas
country: United States
facility: Galenos Research
state: Texas
city: El Paso
country: United States
facility: Sergio F Rovner, MD
state: Texas
city: Houston
country: United States
facility: Salim Gopalani, MD, PA
state: Texas
city: Houston
country: United States
facility: Humayun Mirza, MD, PA
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Houston
country: United States
facility: Houston Clinical Research Assoc.
state: Texas
city: Hurst
country: United States
facility: Innovative Research of West Florida
state: Texas
city: Plano
country: United States
facility: North Texas Medical Research
state: Texas
city: Temple
country: United States
facility: Scott & White Memorial Hospital
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care/University of Vermont
state: Vermont
city: Hopewell
country: United States
facility: Kamlesh N. Dave Cardiology
state: Virginia
city: Charleston
country: United States
facility: WVU Physicians of Charleston
state: West Virginia
city: Madison
country: United States
facility: Alpha Medical Research, LLC
state: Wisconsin
city: Madison
country: United States
facility: Executive Health and Research Associates
state: Wisconsin
city: Bahia Blanca
country: Argentina
facility: Hospital Italiano Regional del Sur
state: Buenos Aires
city: Bahia Blanca
country: Argentina
facility: Instituto de Investigaciones Clinicas Bahia Blanca
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clinicas Mar del Plata
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Consultorios Medicos Privados S.A.
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos "Dr. Abel Zubizarreta"
city: Buenos Aires
country: Argentina
facility: Policlinica Bancaria "9 de Julio"
city: Ciudad de Buenos Aires
country: Argentina
facility: Diabaid (Instituto de Asistencia Integral en Diabetes)
city: Ciudad de Buenos Aires
country: Argentina
facility: MD Investigaciones
city: Ciudad de
country: Argentina
facility: Centro Medico Privado
city: Cordoba
country: Argentina
facility: Fundacion Rusculleda
city: Corrientes
country: Argentina
facility: Instituto de Cardiologia de Corrientes
city: La Plata
country: Argentina
facility: Framingham Centro Medico
city: Quilmes
country: Argentina
facility: Instituto de Investigaciones Clinicas de Quilmes
city: Rosario
country: Argentina
facility: Instituto de Investigaciones Clinicas
city: Santa Fe
country: Argentina
facility: Centro de Investigaciones Clinicas del Litoral
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
city: Melbourne
country: Australia
facility: Alfred Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Brussel
country: Belgium
facility: U.Z. Brussel
city: De Pinte
country: Belgium
facility: Private Practice of Dr. Geert Hollanders
city: Genk
country: Belgium
facility: Private Practice of Dr. Francis Vrancken
city: Genk
country: Belgium
facility: Private Practice of Dr. Herwig Van Aerde
city: Genk
country: Belgium
facility: Private Practice of Dr. Willy Denier
city: Hoeilaart
country: Belgium
facility: Private Practice of Dr. Herman Docx
city: Natoye
country: Belgium
facility: Private Practice of Dr. Yohan Balthazar
city: Pulle
country: Belgium
facility: Private Practice of Dr. Sophie Baeyens
city: Riemst
country: Belgium
facility: Private Practice of Dr. Jean Gilissen
city: Tielt
country: Belgium
facility: Private Practice of Dr. Guido Mehuys
city: Wetteren
country: Belgium
facility: Private Practice of Dr. Luc Capiau
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitario Pedro Ernesto
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Naestved
country: Denmark
facility: Region Sjaelland, Storstrommens Sygenhus, Naestved
city: Blois
country: France
facility: George Delamare
city: Dommartin les Toul
country: France
facility: Centre d'Investigation Clinique
city: La Jubaudiere
country: France
facility: Private Practice of Dr. Brune Charrier
city: Le Mesnil en vallee
country: France
facility: Private Practice of Dr. Jean Boulet-Gercourt
city: Le Temple-de-Bretagne
country: France
facility: Private Practice of Dr. Gildas Ganuchaud
city: Martigues
country: France
facility: Private Practice of Dr. Jacques Samat
city: Murs-Erigne
country: France
facility: Private Practice of dr. Marty Jacques
city: Nantes
country: France
facility: Private Practice of Dr. Alain Boye
city: Nantes
country: France
facility: Private Practice of Dr. Francois Volny
city: Vihiers
country: France
facility: Private Practice of Dr. Thierry Schaupp
city: Bad Worishofen
country: Germany
facility: Private Practice of Dr. Josef Junggeburth
city: Berlin
country: Germany
facility: Charite Campus Mitte, Universitatsmedizin Berlin
city: Berlin
country: Germany
facility: Klinische Forschung Berlin-Buch GmbH
city: Berlin
country: Germany
facility: Private Practice of Dr. Isabelle Schenkenberger
city: Frankfurt
country: Germany
facility: PD Dr. med. Bernhard Winkelmann
city: Hamburg
country: Germany
facility: Clinical Research Hamburg
city: Hamburg
country: Germany
facility: Dr. Med. Susanne Mindt-Prufert
city: Heidelberg
country: Germany
facility: Private Practice for Internal Medicine & Cardiology
city: Koeln
country: Germany
facility: Private Practice of Dr. Tobias Marsen
city: Ruedersdorf
country: Germany
facility: IFG-Institut fur Gesundheitsforderung GmbH
city: Auckland
country: New Zealand
facility: Centre for Clinical Research and Effective Practice (CCRep)
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Greenlane
country: New Zealand
facility: Greenlane Clinical Centre
city: Hamilton
country: New Zealand
facility: Cardiology Clinical Trial Unit
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
Study officials:
References:
citation: Bakris GL, Lindholm LH, Black HR, Krum H, Linas S, Linseman JV, Arterburn S, Sager P, Weber M. Divergent results using clinic and ambulatory blood pressures: report of a darusentan-resistant hypertension trial. Hypertension. 2010 Nov;56(5):824-30. doi: 10.1161/HYPERTENSIONAHA.110.156976. Epub 2010 Oct 4.