关于钠尿肽 ularitide 治疗难治性肝硬化腹水安全性的随机临床试验。

IF 5.6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Hepatology Communications Pub Date : 2024-06-27 eCollection Date: 2024-07-01 DOI:10.1097/HC9.0000000000000481
Rasmus H Gantzel, Emilie E Møller, Niels K Aagaard, Hugh Watson, Peter Jepsen, Henning Grønbæk
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引用次数: 0

摘要

背景:钠和水潴留是导致晚期肝硬化患者腹水形成的主要病理生理因素。难治性腹水是最严重的腹水状态,治疗方案有限,预后较差。我们研究了钠尿肽乌拉利肽对难治性肝硬化腹水患者的疗效和安全性:我们进行了一项随机安慰剂对照试验,研究用乌拉利肽治疗难治性腹水。直到中期分析后试验终止,我们按照 2:1 的比例将 17 名参与者随机分配到乌拉利肽(11 人)和安慰剂(6 人)中。在住院期间,参与者接受了长达 48 小时的治疗。主要疗效终点是肾水排泄量的变化,次要终点包括肾钠排泄率和体重的变化。起始剂量为 30 纳克/千克/分钟,后来出于安全考虑降至 20 纳克/千克/分钟:结果:与研究假设相反,与基线水平相比,乌拉利肽治疗 24 小时后的平均尿量有所减少(22.8 对 47.5 毫升/小时,P=0.04),随机接受乌拉利肽治疗的参与者的尿量减少幅度大于安慰剂(24.7 对 -6.2 毫升/小时,P=0.05)。乌拉利肽没有增加肾钠排泄率或减少体重增加。乌拉利肽与安慰剂的不良反应发生率比为8.5(95% CI:2-35,P=0.003)。接受乌拉利肽治疗的参与者出现了严重的血压下降,影响了他们的肾脏反应能力:结论:20-30 纳克/公斤/分钟剂量的乌拉利肽对难治性腹水患者的尿量和肾脏钠排泄率没有益处。与安慰剂相比,随机接受乌拉利肽治疗的患者总体上出现了更多不良反应。EudraCT 编号:2019-002268-28。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Randomized clinical trial on safety of the natriuretic peptide ularitide as treatment of refractory cirrhotic ascites.

Background: Sodium and water retention is a mainstay of the pathophysiology leading to ascites formation in patients with advanced cirrhosis. Refractory ascites denotes the most severe ascites status with limited treatment options and a poor prognosis. We investigated the efficacy and safety of the natriuretic peptide ularitide in patients with refractory cirrhotic ascites.

Methods: We conducted a randomized placebo-controlled trial investigating ularitide to manage refractory ascites. Until trial termination after interim analyses, we randomized 17 participants in a 2:1 ratio between ularitide (n=11) and placebo (n=6). While hospitalized, the participants received treatment for up to 48 hours. The primary efficacy endpoint was a change in renal water excretion, and secondary end points included changes in renal sodium excretion rate and body weight. The starting dose was 30 ng/kg/min, though later reduced to 20 for safety reasons.

Results: In contrast to the study hypothesis, the mean urine production decreased after 24 hours of ularitide treatment compared with the baseline level (22.8 vs. 47.5 mL/h, p=0.04) and decreased more in participants randomized to ularitide than placebo (24.7 vs. -6.2 mL/h, p=0.05). Ularitide did not increase the renal sodium excretion rate or reduce the weight gain. The incidence rate ratio of adverse reactions in ularitide versus placebo was 8.5 (95% CI: 2-35, p=0.003). Participants treated with ularitide developed serious blood pressure reductions, impacting their renal responsiveness.

Conclusions: Ularitide in doses of 20-30 ng/kg/min did not benefit urine production and renal sodium excretion rate in patients with refractory ascites. The participants randomized to ularitide overall developed more adverse reactions than placebo. EudraCT no. 2019-002268-28.

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来源期刊
Hepatology Communications
Hepatology Communications GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
8.00
自引率
2.00%
发文量
248
审稿时长
8 weeks
期刊介绍: Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction. ​
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