A phase 2 randomised controlled trial of serelaxin to lower portal pressure in cirrhosis (STOPP).
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ABSTRACT:
SUBMITTER: Gifford FJ
PROVIDER: S-EPMC7066808 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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A phase 2 randomised controlled trial of serelaxin to lower portal pressure in cirrhosis (STOPP).
Gifford Fiona J FJ Dunne Philip D J PDJ Weir Graeme G Ireland Hamish H Graham Catriona C Tuck Sharon S Hayes Peter C PC Fallowfield Jonathan A JA
Trials 20200312 1
<h4>Background</h4>In preclinical models, recombinant human relaxin-2 (serelaxin) had anti-fibrotic effects and ameliorated portal hypertension (PH). A small exploratory study in patients with cirrhosis also suggested that serelaxin could reduce portal pressure.<h4>Methods</h4>In a phase 2, double-blind, randomised controlled study conducted in a single centre (Royal Infirmary of Edinburgh, UK), male and female adult participants with cirrhosis and clinically significant PH (CSPH; hepatic venous ...[more]
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Project description:Background: Portal hypertension is one of the most frequent complications of cirrhosis. ?-adrenergic blockers, with or without organic nitrates, are currently used as hypotensive agents. Statins such as simvastatin seem to be safe for patients with chronic liver diseases and exert multiple pleiotropic actions. This study aimed to assess PTH using Doppler ultrasound in patients with cirrhosis before and after simvastatin administration. Methods: This randomized controlled clinical trial was conducted on 40 patients with cirrhosis who were randomized into 2 groups: group I included 20 patients with cirrhosis who were administered 20 mg of simvastatin daily for 2 weeks and then 40 mg daily for another 2 weeks, and group II included 20 patients with cirrhosis who did not receive simvastatin as a control group. All patients underwent full clinical examination, laboratory investigations, and abdominal Doppler ultrasound at baseline and after 30 days to evaluate portal vein diameter, blood flow volume, direction and velocity of portal vein blood flow, hepatic artery resistance and pulsatility indices, splenic artery resistance index, portal hypertension index (PHI), liver vascular index, and modified liver vascular index (MLVI). Results: There was a highly significant decrease in the hepatic artery resistance index in group I, from 0.785 ± 0.088 to 0.717 ± 0.086 (P < 0.001). There was a significant decrease in the PHI in group I , from 3.915 ± 0.973 m/sec to 3.605 ± 1.168 m/sec (P = 0.024). Additionally, there was a significant increase in the MLVI in group I from 11.540 ± 3.266 cm/sec to 13.305 ± 3.222 cm/sec, an increase of 15.3% from baseline (P = 0.009). No significant adverse effects were detected. Conclusions: Simvastatin is safe and effective in lowering portal hypertension. [ClinicalTrials.gov Identifier: NCT02994485].
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