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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00389779




Registration number
NCT00389779
Ethics application status
Date submitted
17/10/2006
Date registered
19/10/2006
Date last updated
18/03/2014

Titles & IDs
Public title
DORADO-AC - Optimized Doses of Darusentan as Compared to an Active Control in Resistant Hypertension
Scientific 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)
Secondary ID [1] 0 0
Protocol DAR-312
Universal Trial Number (UTN)
Trial acronym
Darusentan
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Darusentan
Treatment: Drugs - Guanfacine
Treatment: Drugs - Darusentan Placebo

Experimental: Darusentan - Placebo to match darusentan for 2-week placebo run-in period, followed by darusentan capsules titrated to an optimal dose of 50 mg, 100 mg, or 300 mg administered orally once daily for 14 weeks

Active comparator: Guanfacine - Placebo to match darusentan for 2-week placebo run-in period, followed by guanfacine 1 mg capsules administered orally once daily for 14 weeks

Placebo comparator: Darusentan Placebo - Placebo to match darusentan for 2-week placebo run-in period, followed by placebo to match darusentan administered orally once daily for 14 weeks


Treatment: Drugs: Darusentan
Darusentan capsules administered orally once daily

Treatment: Drugs: Guanfacine
Guanfacine capsules administered orally once daily

Treatment: Drugs: Darusentan Placebo
Placebo to match darusentan administered orally once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in trough sitting systolic and diastolic blood pressure measured by sphygmomanometry
Timepoint [1] 0 0
Baseline to Week 14
Secondary outcome [1] 0 0
Percentage of subjects reaching systolic blood pressure goal after 14 weeks of treatment
Timepoint [1] 0 0
Week 14
Secondary outcome [2] 0 0
Change from baseline in mean 24-hour systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring (ABPM)
Timepoint [2] 0 0
Baseline to Week 14
Secondary outcome [3] 0 0
Change from baseline in estimated glomerular filtration rate (eGFR)
Timepoint [3] 0 0
Baseline to Week 14

Eligibility
Key inclusion 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
Minimum age
35 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2009
Sample size
Target
Accrual to date
Final
849
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [3] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [4] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Bedford Park
Recruitment postcode(s) [2] 0 0
- Herston
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Perth
Recruitment outside Australia
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Martigues
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Nantes
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Vihiers
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Koeln
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Ruedersdorf
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Auckland
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New Zealand
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Christchurch
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Greenlane
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Hamilton
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Barcelona
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00389779
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00389779