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

• Main Authors: Citterio Lorena, Lanzani Chiara, Souček Miroslav, Nikitin Yuri, Milyagin Viktor, Manunta Paolo, Januszewicz Andrzej, Glorioso Nicola, Dłużniewski Mirosław, de Leeuw Peter W, Espositi Ezio, Barton John, Bacchieri Antonella, Stolarz-Skrzypek Katarzyna, Thijs Lutgarde, Staessen Jan A, Timio Mario, Tykarski Andrzej, Ferrari Patrizia, Valentini Giovanni, Kawecka-Jaszcz Kalina, Bianchi Giuseppe
• Format: Article
• Language: English
• Published: BMC 2011-01-01
• Series: Trials
• Online Access: http://www.trialsjournal.com/content/12/1/13
• ISSN: 1745-6215

<p/> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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).</p> <p>Results</p> <p>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 (<it>P </it>= 0.90) on 0.15 mg/d rostafuroxin to 2.72 mm Hg (<it>P </it>= 0.04) on 0.05 mg/d. In the 5 dosage arms combined, the treatment effects averaged 1.30 mm Hg (<it>P </it>= 0.03) for systolic office BP; 0.70 mm Hg (<it>P </it>= 0.08) for diastolic office BP; 0.36 mm Hg (<it>P </it>= 0.49) for 24-h systolic BP; and 0.05 mm Hg (<it>P </it>= 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 (<it>P </it>for period effect ≤0.028), but carry-over effects were not significant (<it>P </it>≥ 0.11). All other endpoints were not different on rostafuroxin and placebo. Minor side-effects occurred with similarly low frequency on rostafuroxin and placebo.</p> <p>Conclusions</p> <p>In 5 concurrently running double-blind cross-over studies rostafuroxin did not reduce BP at any dose.</p> <p>Trial Registration</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT00415038">NCT00415038</a></p>