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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

Staessen, Jan A
Thijs, Lutgarde
Stolarz-Skrzypek, Katarzyna
Bacchieri, Antonella
Barton, John
Espositi, Ezio degli
de Leeuw, Peter W
Dłużniewski, Mirosław
Glorioso, Nicola
Januszewicz, Andrzej
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Citation
Staessen, Jan A; Thijs, Lutgarde; Stolarz-Skrzypek, Katarzyna; Bacchieri, Antonella; Barton, John; Espositi, Ezio degli; de Leeuw, Peter W; Dłużniewski, Mirosław; Glorioso, Nicola; Januszewicz, Andrzej; Manunta, Paolo; Milyagin, Viktor; Nikitin, Yuri; Souček, Miroslav; Lanzani, Chiara; Citterio, Lorena; Timio, Mario; Tykarski, Andrzej; Ferrari, Patrizia; Valentini, Giovanni; Kawecka-Jaszcz, Kalina; Bianchi, Giuseppe (2011). 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. Trials 12 ,
Abstract
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.
Funder
Publisher
Springer Nature
Publisher DOI
10.1186/1745-6215-12-13
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland