Efficacy of solnatide to treat pulmonary permeability edema in SARS-CoV-2 positive patients with moderate to severe ARDS: A randomized controlled pilot-trial

IF 3.7 3区医学 Q1 ANESTHESIOLOGY

Anaesthesia Critical Care & Pain Medicine Pub Date : 2025-05-01 DOI:10.1016/j.accpm.2025.101520

Katharina Krenn , Felix Kraft , Matthias Urban , Roman Ullrich , Erwin Grasmuk-Siegl , Georg Gelbenegger , Martin Bauer , Valentin Al Jalali , Karolina Anderle , Anselm Jorda , Maria Weber , Arschang Valipour , Franz König , Rudolf Lucas , Markus Zeitlinger

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Abstract

Background

Because of the initially urgent need for treatments for COVID-19-associated acute respiratory distress syndrome (ARDS), the efficacy and tolerability of inhaled solnatide, a direct activator of the epithelial sodium channel (ENaC) under clinical investigation for the treatment of ARDS, were assessed in a pilot trial.

Methods

This randomized controlled double-blind clinical trial was performed at two study centers in Vienna, Austria. Adult mechanically ventilated patients with moderate to severe ARDS (Berlin Definition) caused by COVID-19 were randomized 1:1 to inhalation of solnatide (100 mg) or placebo twice daily for seven days. The primary outcome parameter was ventilator-free days (VFDs) within 28 days; survival was assessed at 28 and 60 days as a secondary outcome.

Results

A total of 30 out of the 40 planned patients were included, 15 randomized to solnatide and 15 to placebo. Then the trial was stopped early due to slow recruitment. The median VFDs were 0 in both groups (p =  0.653). Twenty out of 30 patients (66.7%) survived until day 28 [solnatide group: n = 11 (73.3%), placebo group: n = 9 (60%)]. One additional patient per group died until day 60. In total, 41 adverse events (AEs) and 10 serious AEs occurred in the solnatide group, and 26 AEs and 14 serious AEs in the placebo group. No AE was considered to be related to the study treatment.

Conclusions

There was no difference in VFDs or survival between the solnatide and the placebo group. Solnatide appeared safe in this limited cohort of critically ill patients with COVID-19.

Registration

EU clinical trials register, EudraCT number 2020-001244-26.

Abstract Image

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索那肽治疗SARS-CoV-2阳性中重度ARDS患者肺通透性水肿的疗效：一项随机对照试验

由于对covid -19相关急性呼吸窘迫综合征（ARDS）治疗的最初迫切需要，在一项试点试验中评估了吸入solnatide（一种上皮钠通道（ENaC）的直接激活剂）治疗ARDS的疗效和耐受性。方法在奥地利维也纳的两个研究中心进行随机对照双盲临床试验。由COVID-19引起的中度至重度ARDS（柏林定义）的成人机械通气患者按1:1随机分组，每天两次吸入solnatide（100 mg）或安慰剂，连续7天。主要结局参数为28天内无呼吸机天数（vfd）；28天和60天生存率作为次要指标进行评估。结果共纳入40例计划患者中的30例，其中15例随机分配到索拉肽组，15例随机分配到安慰剂组。后来由于招募缓慢，试验提前停止。两组中位vfd均为0 （p = 0.653）。30例患者中有20例（66.7%）存活至28天[索拉肽组：n = 11例（73.3%），安慰剂组：n = 9例（60%）]。每组增加1例患者死亡至第60天。索拉肽组共发生41例不良事件和10例严重不良事件，安慰剂组发生26例不良事件和14例严重不良事件。没有AE被认为与研究治疗有关。结论索拉肽组与安慰剂组在vfd和生存率方面无显著差异。在这个有限的COVID-19危重患者队列中，索那肽是安全的。欧盟临床试验注册，EudraCT号2020-001244-26。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anaesthesia Critical Care & Pain Medicine ANESTHESIOLOGY-

CiteScore

6.70

自引率

5.50%

发文量

150

审稿时长

18 days

期刊介绍： Anaesthesia, Critical Care & Pain Medicine (formerly Annales Françaises d''Anesthésie et de Réanimation) publishes in English the highest quality original material, both scientific and clinical, on all aspects of anaesthesia, critical care & pain medicine.