Staessen, Jan A. and Thijs, Lutgarde and Stolarz-Skrzypek, Katarzyna and Bachieri, Antonella and Barton, John and Degli Espositi, Ezio and De Leeuw, Peter W. and Dluzniewski, Miroslaw and Glorioso, Nicola and Januszewicz, Andrzej and Manunta, Paolo and Milyagin, Viktor and Nikitin, Yuri and Souček, Miroslav and Lanzani, Chiara and Citterio, Lorena and Timio, Mario and Tykarski, Andrzej and Ferrari, Patrizia and Valentini, Giovanni and Kawecka-Jaszcz, Kalina and 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, Vol. 12 (1), p. 1-37. eISSN 1745-6215. Article.
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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 deivative, 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.
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).
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.
In 5 concurrently running double-blind cross-over studies rostafuroxin did not reduce BP at any dose. Trial Registration: NCT00415038 http://www.clinicaltrials.gov).
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