The Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Research, University of Leuven, Leuven, Belgium.
Trials. 2011 Jan 14;12:13. doi: 10.1186/1745-6215-12-13.
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.
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.
ClinicalTrials (NCT): NCT00415038.
Ouabain 和 Adducin 用于高血压钠的特定干预（OASIS-HT）试验是一种对 rostarufuroxin 的 2 期剂量发现研究，rostarufuroxin 是一种 digitoxygenin 衍生物，可选择性拮抗内源性哇巴因（EO）对 Na+，K+-ATPase 和突变的粘附素的作用。Rostafuroxin 降低了一些动物模型和人类的血压（BP）。
OASIS-HT 由 5 项同时进行的双盲交叉研究组成。经过 4 周的无治疗期后，435 名患有单纯收缩期高血压（140-169mmHg）的患者被随机分配至 rostarufuroxin（0.05、0.15、0.5、1.5 或 5.0mg/d）或匹配的安慰剂，每个治疗期持续 5 周。主要终点是收缩压办公室血压的降低。次要终点包括舒张压办公室血压、24 小时动态血压、血浆 EO 浓度和肾素活性、24 小时尿钠和醛固酮排泄以及安全性。方差分析考虑了治疗顺序（固定效应）、序列内的受试者（随机）、周期（固定）和治疗（固定）。
在 410 名可分析患者（40.5%为女性；平均年龄为 48.4 岁）中，主要终点（rostafuroxin 减去安慰剂）的差异范围为 0.15mg/d rostafuroxin 为-0.18mmHg（P=0.90）至 0.05mg/d rostafuroxin 为 2.72mmHg（P=0.04）。在 5 个剂量臂联合治疗中，治疗效果平均为收缩压办公室血压 1.30mmHg（P=0.03）；舒张压办公室血压 0.70mmHg（P=0.08）；24 小时收缩压 0.36mmHg（P=0.49）；24 小时舒张压 0.05mmHg（P=0.88）。在联合治疗组中，收缩压（-1.36mmHg）和舒张压（-0.97mmHg）办公室血压从第 5 周到第 10 周下降（P 值≤0.028），但无明显的药物持续作用（P≥0.11）。Rostafuroxin 和安慰剂对其他所有终点均无差异。Rostafuroxin 和安慰剂的不良反应发生率相似且较低。
在 5 项同时进行的双盲交叉研究中，任何剂量的 rostarufuroxin 均未降低血压。
ClinicalTrials（NCT）：NCT00415038。
