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Trials
Published in: Trials 1/2011

Open Access 01-12-2011 | Research

Main results of the Ouabain and Adducin for Specific Intervention on Sodium in Hypertension Trial (OASIS-HT): a randomized placebo-controlled phase-2 dose-finding study of rostafuroxin

Authors: Jan A Staessen, Lutgarde Thijs, Katarzyna Stolarz-Skrzypek, Antonella Bacchieri, John Barton, Ezio degli Espositi, Peter W de Leeuw, Mirosław Dłużniewski, Nicola Glorioso, Andrzej Januszewicz, Paolo Manunta, Viktor Milyagin, Yuri Nikitin, Miroslav Souček, Chiara Lanzani, Lorena Citterio, Mario Timio, Andrzej Tykarski, Patrizia Ferrari, Giovanni Valentini, Kalina Kawecka-Jaszcz, Giuseppe Bianchi

Published in: Trials | Issue 1/2011

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Background

The Ouabain and Adducin for Specific Intervention on Sodium in Hypertension (OASIS-HT) Trial was a phase-2 dose-finding study of rostafuroxin, a digitoxygenin derivative, which selectively antagonizes the effects of endogenous ouabain (EO) on Na+,K+-ATPase and mutated adducin. Rostafuroxin lowered blood pressure (BP) in some animal models and in humans.

Methods

OASIS-HT consisted of 5 concurrently running double-blind cross-over studies. After 4 weeks without treatment, 435 patients with uncomplicated systolic hypertension (140-169 mm Hg) were randomized to rostafuroxin (0.05, 0.15, 0.5, 1.5 or 5.0 mg/d) or matching placebo, each treatment period lasting 5 weeks. The primary endpoint was the reduction in systolic office BP. Among the secondary endpoints were diastolic office BP, 24-h ambulatory BP, plasma EO concentration and renin activity, 24-h urinary sodium and aldosterone excretion, and safety. ANOVA considered treatment sequence (fixed effect), subjects nested within sequence (random), period (fixed), and treatment (fixed).

Results

Among 410 analyzable patients (40.5% women; mean age, 48.4 years), the differences in the primary endpoint (rostafuroxin minus placebo) ranged from -0.18 mm Hg (P = 0.90) on 0.15 mg/d rostafuroxin to 2.72 mm Hg (P = 0.04) on 0.05 mg/d. In the 5 dosage arms combined, the treatment effects averaged 1.30 mm Hg (P = 0.03) for systolic office BP; 0.70 mm Hg (P = 0.08) for diastolic office BP; 0.36 mm Hg (P = 0.49) for 24-h systolic BP; and 0.05 mm Hg (P = 0.88) for 24-h diastolic BP. In the 2 treatment groups combined, systolic (-1.36 mm Hg) and diastolic (-0.97 mm Hg) office BPs decreased from week 5 to 10 (P for period effect ≤0.028), but carry-over effects were not significant (P ≥ 0.11). All other endpoints were not different on rostafuroxin and placebo. Minor side-effects occurred with similarly low frequency on rostafuroxin and placebo.

Conclusions

In 5 concurrently running double-blind cross-over studies rostafuroxin did not reduce BP at any dose.

Trial Registration

ClinicalTrials (NCT): NCT00415038
Appendix
Available only for authorised users
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Metadata
Title
Main results of the Ouabain and Adducin for Specific Intervention on Sodium in Hypertension Trial (OASIS-HT): a randomized placebo-controlled phase-2 dose-finding study of rostafuroxin
Authors
Jan A Staessen
Lutgarde Thijs
Katarzyna Stolarz-Skrzypek
Antonella Bacchieri
John Barton
Ezio degli Espositi
Peter W de Leeuw
Mirosław Dłużniewski
Nicola Glorioso
Andrzej Januszewicz
Paolo Manunta
Viktor Milyagin
Yuri Nikitin
Miroslav Souček
Chiara Lanzani
Lorena Citterio
Mario Timio
Andrzej Tykarski
Patrizia Ferrari
Giovanni Valentini
Kalina Kawecka-Jaszcz
Giuseppe Bianchi
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Trials / Issue 1/2011
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-12-13

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