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A Study to Test Whether Two Different Doses of Avenciguat Help People With Liver Cirrhosis and High Blood Pressure in the Portal Vein (Main Vessel Going to the Live

Phase 2
Terminated
Conditions
Hypertension, Portal
Registration Number
NCT05161481
Lead Sponsor
Boehringer Ingelheim
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Terminated
Sex
All
Target Recruitment
80
Inclusion Criteria

Inclusion Criteria:<br><br> 1. Signed and dated written informed consent in accordance with International Council<br> on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to<br> admission to the trial<br><br> 2. Male or female who is = 18 (or who is of legal age in countries where that is<br> greater than 18) and = 75 years old at screening<br><br> 3. Clinical signs of Clinically Significant Portal Hypertension (CSPH) as described by<br> either one of the points below. Each trial patient must have a gastroscopy during<br> the screening period or within 6 months prior to screening.<br><br> - documented endoscopic proof of oesophageal varices and / or gastric varices at<br> screening or within 6 months prior to screening<br><br> - documented endoscopic-treated oesophageal varices as preventative treatment<br><br> 4. CSPH defined as baseline Hepatic Venous Pressure Gradient (HVPG) = 10 mmHg, based on<br> a local interpretation of the pressure tracing<br><br> 5. Diagnosis of compensated alcohol-related cirrhosis. Diagnosis must be based on<br> histology (historical data is acceptable) or on clinical evidence of cirrhosis (e.g.<br> platelet count < 150 x 10^9/L [150 x 10^3/µL], nodular liver surface on imaging or<br> splenomegaly)<br><br> 6. Abstinence from significant alcohol misuse / abuse for a minimum of 2 months prior<br> to screening, and the ability to abstain from alcohol throughout the trial (both<br> evaluated based on Investigator judgement)<br><br> 7. Willing and able to undergo HVPG measurements per protocol (based on Investigator<br> judgement)<br><br> 8. If receiving statins must be on a stable dose for at least 3 months prior to<br> screening, with no planned dose change throughout the trial Further inclusion<br> criteria apply.<br><br>Exclusion Criteria:<br><br> 1. Previous clinically significant decompensation events (e.g. ascites [more than<br> perihepatic ascites], Variceal Haemorrhage (VH) and / or apparent Hepatic<br> Encephalopathy (HE))<br><br> 2. History of other forms of chronic liver disease (e.g. non-alcoholic steatohepatitis<br> (NASH), Hepatitis B virus (HBV), untreated Hepatitis C Virus (HCV), autoimmune liver<br> disease, primary biliary cholangitis, primary sclerosing cholangitis, Wilson's<br> disease, haemachromatosis, alpha-1 antitrypsin (A1At) deficiency)<br><br> 3. Has received curative anti-viral therapy with direct-acting anti-virals within the<br> last 2 years for HCV, or, if such treatment was > 2 years ago and there is no<br> sustained virological response (SVR) at screening, or, must take curative anti-viral<br> therapy with direct-acting anti-virals throughout the trial<br><br> 4. Alcohol-Related Liver Disease (ARLD) without adequate treatment (e.g. lifestyle<br> modification) or with ongoing pathological drinking behaviour (misuse / abuse based<br> on Investigator judgement)<br><br> 5. Must take, or wishes to continue the intake of, restricted concomitant therapy or<br> any concomitant therapy considered likely (based on Investigator judgement) to<br> interfere with the safe conduct of the trial<br><br> 6. Systolic Blood Pressure (SBP) < 100 mmHg and Diastolic Blood Pressure (DBP) < 70<br> mmHg at screening<br><br> 7. Model of End-stage Liver Disease (MELD) score of > 15 at screening, calculated by<br> the central laboratory<br><br> 8. Hepatic impairment defined as a Child-Turcotte-Pugh score = B8 at screening,<br> calculated by the site, using central laboratory results Further exclusion criteria<br> apply.

Exclusion Criteria

Not provided

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Percentage change in Hepatic Venous Pressure Gradient (HVPG) from baseline (measured in mmHg) after 24 weeks of treatment
Secondary Outcome Measures
NameTimeMethod
Percentage change in HVPG from baseline (measured in mmHg) after 8 weeks of treatment;Response defined as > 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatment;Response defined as > 10% reduction from baseline HVPG (measured in mmHg) after 24 weeks of treatment;Occurrence of one or more decompensation events (i.e. ascites, Variceal Haemorrhage (VH), and/or overt Hepatic Encephalopathy (HE)) during the 24 week treatment period;Occurrence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the first 8 weeks of the treatment period;Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 24 week treatment period;Occurrence of discontinuation due to hypotension or syncope during the first 8 weeks of the treatment period;Occurrence of discontinuation due to hypotension or syncope during the 24 week treatment period
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