What side effects are associated with this type of intervention?

Common treatments for portal hypertension, such as soluble guanylate cyclase stimulators like Avenciguat, often have side effects including headache, dizziness, hypotension, gastrointestinal issues (nausea, vomiting, diarrhea), and flushing. In patients with liver cirrhosis, there may also be specific concerns related to liver function. It is important to monitor these side effects closely and discuss them with a healthcare provider.

What prior FDA approvals exist?

There are no specific mentions of FDA-approved soluble guanylate cyclase stimulators for the treatment of portal hypertension in the provided context. However, soluble guanylate cyclase stimulators like riociguat and vericiguat have been studied for other conditions such as pulmonary hypertension and heart failure. For portal hypertension, treatments often include beta blockers like carvedilol and nonselective beta blockers such as nadolol and propranolol, which help reduce portal pressure and prevent variceal bleeding.

What other types of research exist?

Promising novel alternatives to Avenciguat for treating portal hypertension in 2024 include: <ol> <li>Eltrombopag: A thrombopoietin receptor agonist, though it carries a risk of thrombosis in the portal venous system.</li> <li></li> </ol> Enoxaparin: An anticoagulant that may prevent portal vein thrombosis in cirrhosis patients. 3. Endothelin Receptor Antagonists (e.g., Bosentan, Macitentan): These have been studied for their effects on pulmonary hypertension and may have potential applications in portal hypertension, though fluid retention is a concern. 4. PDE-5 Inhibitors (e.g., Sildenafil): These have shown favorable impacts on hemodynamic variables in small studies and may be considered for further research in portal hypertension.

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BI 685509 for Portal Hypertension

Phase 2

Recruiting

Research Sponsored by Boehringer Ingelheim

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Signed and dated written informed consent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial

Male or female who is ≥ 18 (or who is of legal age in countries where that is greater than 18) and ≤ 75 years old at screening

Must not have

Previous clinically significant decompensation events (e.g. ascites [more than perihepatic ascites], Variceal Haemorrhage (VH) and / or apparent Hepatic Encephalopathy (HE))

History of other forms of chronic liver disease (e.g. non-alcoholic steatohepatitis (NASH), Hepatitis B virus (HBV), untreated Hepatitis C Virus (HCV), autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilson's disease, haemachromatosis, alpha-1 antitrypsin (A1At) deficiency)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 weeks

Summary

This trial tests if Avenciguat helps adults with liver cirrhosis and high blood pressure in the portal vein. Participants take either Avenciguat or another treatment for several months. Doctors measure blood pressure in the liver to see if the medicine works.

Who is the study for?

Adults aged 18-75 with compensated alcohol-related liver cirrhosis and clinically significant portal hypertension can join. They must not have severe liver impairment, history of other chronic liver diseases, or recent treatments for Hepatitis C without sustained response. Participants should be able to undergo specific vein pressure measurements and abstain from significant alcohol use.

What is being tested?

The trial is testing the effectiveness of BI 685509 in treating high blood pressure in the portal vein due to liver cirrhosis. Participants are randomly assigned to receive either one of two different doses of BI 685509 or a placebo, all taken as tablets twice daily over approximately eight months.

What are the potential side effects?

While specific side effects for BI 685509 aren't listed here, participants' health will be monitored regularly for any unwanted effects which may include typical drug reactions such as digestive issues, headaches, fatigue, or potential liver-related complications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have signed and understand the consent form for this trial.

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I am between 18 and 75 years old.

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I have been diagnosed with alcohol-related liver cirrhosis.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had serious liver-related health events like fluid in the abdomen, bleeding varices, or brain fog due to liver issues.

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I have a history of chronic liver disease.

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I have been treated for hepatitis C with specific antiviral drugs within the last 2 years or will take them during the trial.

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My liver function is impaired, with a score indicating moderate to severe issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage change in Hepatic Venous Pressure Gradient (HVPG) from baseline (measured in mmHg) after 24 weeks of treatment

Secondary study objectives

Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, 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 discontinuation due to hypotension or syncope during the 24 week treatment period

+5 more

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Avenciguat (BI 685509), dose group 2Experimental Treatment1 Intervention

Group II: Avenciguat (BI 685509), dose group 1Experimental Treatment1 Intervention

Group III: PlaceboPlacebo Group1 Intervention

Placebo

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for portal hypertension include beta-blockers, which reduce portal pressure by decreasing cardiac output and splanchnic blood flow, and diuretics, which manage fluid retention associated with ascites. Avenciguat, a soluble guanylate cyclase (sGC) stimulator, works by enhancing the nitric oxide (NO) signaling pathway, leading to vasodilation and reduced vascular resistance. This mechanism is particularly important for portal hypertension patients as it directly targets the underlying vascular dysfunction, potentially improving blood flow and reducing portal pressure more effectively than traditional treatments.

Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial.A Hopeful Prospect of Riociguat as a Soluble Guanylate Cyclase Stimulator for Management of Pressure Ulcers.Pulmonary arterial hypertension: a review in pharmacotherapy.