Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
Gut. 2012 Jan;61(1):108-16. doi: 10.1136/gutjnl-2011-300157. Epub 2011 Aug 11.
Satavaptan, a vasopressin V2 receptor antagonist, has been shown to improve the control of ascites in cirrhosis in short-term phase II studies. The aim of this study was to evaluate the efficacy and safety of satavaptan in three different populations of patients with cirrhosis and ascites.
1200 patients were included in three randomised double-blind studies comparing satavaptan with placebo in uncomplicated ascites (study 1: n=463 patients) and difficult-to-treat ascites, with and without concomitant diuretic treatment (studies 2 and 3: n=497 and n=240 patients, respectively).
Satavaptan was not more effective than placebo in the control of ascites in any of the populations studied as estimated by the primary efficacy endpoints: worsening of ascites (study 1) and the cumulative number of large-volume paracenteses during 12 weeks (studies 2 and 3). Nevertheless, some of the secondary efficacy endpoints related to the treatment of ascites were met in the three studies, suggesting a slight advantage of satavaptan over placebo in delaying ascites formation. Moreover, satavaptan was more effective than placebo in improving the serum sodium concentration in patients with hyponatraemia. The incidence of major complications of cirrhosis during follow-up did not differ significantly between the satavaptan and placebo groups in the three studies. Overall, the rate of any treatment-related adverse events, serious treatment-related events and treatment-related events leading to permanent discontinuation of treatment did not differ significantly between the treatment groups. However, in study 2 mortality was higher in patients treated with satavaptan compared with placebo (HR 1.47; 95% CI 1.01 to 2.15); no significant differences in mortality between the two groups were observed in the other two studies. No specific cause for the increased mortality was identified. Most deaths were associated with known complications of liver cirrhosis.
Satavaptan, alone or in combination with diuretics, is not clinically beneficial in the long-term management of ascites in cirrhosis.
作为一种血管加压素 V2 受体拮抗剂，沙他伐坦已被证明可在短期的 II 期研究中改善肝硬化腹水的控制。本研究旨在评估沙他伐坦在三种不同肝硬化腹水患者人群中的疗效和安全性。
在三项随机、双盲研究中，共纳入 1200 例患者，比较沙他伐坦与安慰剂在单纯性腹水（研究 1：n=463 例）和难治性腹水（研究 2 和 3：n=497 例和 n=240 例）患者中的疗效。在难治性腹水患者中，一些患者同时接受利尿剂治疗，另一些患者未接受利尿剂治疗。
在所有研究人群中，沙他伐坦在控制腹水方面均不比安慰剂更有效，这一点可以从主要疗效终点评估得出：腹水恶化（研究 1）和 12 周期间大量腹腔穿刺术的累积次数（研究 2 和 3）。然而，三项研究中的一些与腹水治疗相关的次要疗效终点得到了满足，提示沙他伐坦在延迟腹水形成方面略优于安慰剂。此外，沙他伐坦在改善低钠血症患者的血清钠浓度方面优于安慰剂。在三项研究中，随访期间肝硬化的主要并发症发生率在沙他伐坦组和安慰剂组之间无显著差异。总体而言，两组之间任何治疗相关不良事件、严重治疗相关事件和导致治疗永久终止的治疗相关事件的发生率无显著差异。然而，在研究 2 中，与安慰剂组相比，沙他伐坦治疗组的死亡率更高（HR 1.47；95%CI 1.01 至 2.15）；在其他两项研究中，两组之间的死亡率无显著差异。未确定死亡率增加的具体原因。大多数死亡与肝硬化的已知并发症有关。
沙他伐坦单独或与利尿剂联合使用，在肝硬化腹水的长期管理中并无临床获益。
