OASIS-HT: design of a pharmacogenomic dose-finding study

Details

Serval ID
serval:BIB_9D065882841B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
OASIS-HT: design of a pharmacogenomic dose-finding study
Journal
Pharmacogenomics
Author(s)
Staessen  J. A., Kuznetsova  T., Acceto  R., Bacchieri  A., Brand  E., Burnier  M., Celis  H., Citterio  L., de Leeuw  P. W., Filipovsky  J., Fournier  A., Kawecka-Jaszcz  K., Manunta  P., Nikitin  Y., O'Brien  E. T., Redon  J., Thijs  L., Ferrari  P., Valentini  G., Bianchi  G.
ISSN
1462-2416 (Print)
Publication state
Published
Issued date
10/2005
Volume
6
Number
7
Pages
755-75
Notes
Clinical Trial, Phase II
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't --- Old month value: Oct
Abstract
Experimental evidence and observations in humans strongly support an interactive role of mutated alpha-adducin, sodium (Na(+))/potassium (K(+))-adenosine triphosphatase (ATPase) activity and endogenous ouabain in Na(+) homeostasis and the pathogenesis of hypertension. The Ouabain and Adducin for Specific Intervention on Sodium in HyperTension (OASIS-HT) trial is an early Phase II dose-finding study, which will be conducted across 39 European centers. Following a run-in period of 4 weeks without treatment, eligible patients will be randomized to one of five oral doses of rostafuroxin consisting of 0.05, 0.15, 0.5, 1.5, or 5.0 mg/day. Each dose will be compared to a placebo in a double-blind crossover experiment with balanced randomization. Treatment will be initiated with the active drug and continued with placebo or vice versa. Each double-blind period will last 5 weeks. The primary end point is the reduction in systolic blood pressure defined as the average of three clinic readings with the patient in the sitting position. Secondary end points include the reduction in diastolic blood pressure on clinic measurement, the decrease in the 24-h blood pressure, and the incidence of end points related to safety. Secondary objectives are to investigate the dependence of the blood pressure-lowering activity on the plasma concentration of endogenous ouabain and the genetic variation of the enzymes involved in the metabolism of this hormone, and the adducin cytoskeleton proteins. Eligible patients will have Grade I or II systolic hypertension without associated conditions and no more than two additional risk factors. In conclusion, OASIS-HT is a combination of five concurrent crossover studies, one for each dose of rostafuroxin to be studied. To our knowledge, OASIS-HT is the first Phase II dose-finding study in which a genetic hypothesis is driving primary and secondary end points.
Keywords
Administration, Oral Adult Androstanols/administration & dosage/adverse effects/chemistry/*therapeutic use Antihypertensive Agents/administration & dosage/adverse effects/chemistry/*therapeutic use Blood Pressure/drug effects Calmodulin-Binding Proteins/*metabolism Cross-Over Studies Dose-Response Relationship, Drug Double-Blind Method Drug Administration Schedule Female Humans Hypertension/*drug therapy/*metabolism Male Middle Aged Molecular Conformation Ouabain/*antagonists & inhibitors/chemistry Risk Factors Time Factors Treatment Outcome
Pubmed
Web of science
Create date
25/01/2008 12:55
Last modification date
20/08/2019 15:03
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