Ongoing Clinical Trials for Portal Hypertension
This article provides an overview of 6 ongoing clinical trials investigating new treatments for portal hypertension, a condition characterized by increased blood pressure in the portal vein system. These trials are exploring medications including norfloxacin, telmisartan, carvedilol, metformin, and experimental drugs BI 685509 and empagliflozin across multiple countries in Europe.
Clinical trial locations
- Austria
- Study on BI 685509 and Empagliflozin for Patients with Portal Hypertension in Compensated Cirrhosis
- Study on Norfloxacin for Reducing Portal Hypertension in Patients with Decompensated Cirrhosis
- Study on Telmisartan for Reducing Portal Hypertension in Patients with Advanced Chronic Liver Disease
- Study on the Effects of BI 685509 for Patients with Liver Cirrhosis and Portal Hypertension After First Decompensation Event
- Belgium
- Denmark
- France
- Study on BI 685509 and Empagliflozin for Patients with Portal Hypertension in Compensated Cirrhosis
- Study on the Effect of Carvedilol for Patients with Cirrhotic Portal Hypertension
- Study on the Effects of BI 685509 for Patients with Liver Cirrhosis and Portal Hypertension After First Decompensation Event
- Study on the Effects of Metformin in Patients with Cirrhosis and Portal Hypertension Already Treated with Carvedilol
- Germany
- Italy
- Netherlands
- Romania
- Spain
Study on Norfloxacin for Reducing Portal Hypertension in Patients with Decompensated Cirrhosis
This trial is investigating whether norfloxacin, an antibiotic, can help reduce high blood pressure in the portal vein in patients with decompensated cirrhosis. The study focuses on patients whose liver is severely damaged and cannot function properly.
Main inclusion criteria: Participants must have decompensated cirrhosis and be undergoing a liver vein catheterization procedure to measure pressure in the liver veins. They must be between 18 and 80 years old and provide written informed consent.
Main exclusion criteria: The exclusion criteria appear inconsistent with the study goals, as they mention excluding patients with the conditions being studied. This likely refers to specific subtypes or severity levels not appropriate for this particular trial.
Study focus: The primary goal is to determine whether taking norfloxacin 400 mg daily for 12 weeks can lower the hepatic venous pressure gradient. Throughout the study, researchers will monitor liver-related complications and assess patients’ quality of life. The trial is double-blinded, meaning neither participants nor researchers know who receives the actual medication or placebo.
Investigational drug: Norfloxacin is an antibiotic that works by inhibiting bacterial DNA replication. The trial investigates whether it can reduce bacterial infections that worsen liver conditions and thereby lower pressure in the portal vein system.
Study on Telmisartan for Reducing Portal Hypertension in Patients with Advanced Chronic Liver Disease
This study examines whether telmisartan, a medication commonly used to treat high blood pressure, can help reduce pressure in liver veins in patients with compensated advanced chronic liver disease. In this condition, the liver is significantly damaged but still able to perform its basic functions.
Main inclusion criteria: Patients must be 18 to 79 years old with compensated advanced chronic liver disease and clinically significant portal hypertension, defined as a hepatic venous pressure gradient of 10 mmHg or more. They must have a Child-Pugh stage of A or B and a MELD score of 15 or less.
Main exclusion criteria: The trial excludes patients with uncontrolled high blood pressure, severe heart problems, unstable kidney issues, previous liver transplant, active infections requiring treatment, pregnancy or breastfeeding, current participation in another trial, recent alcohol or drug abuse, mental health conditions affecting study compliance, and allergies to the study medication.
Study focus: Participants take telmisartan 40 mg or placebo once daily for 12 weeks. The main goal is to measure the difference in hepatic venous pressure gradient from the start to the end of treatment. Regular monitoring includes assessments of liver and spleen stiffness.
Investigational drug: Telmisartan is an angiotensin II receptor blocker that helps relax and widen blood vessels by blocking substances that cause vessels to tighten. The trial explores whether this mechanism can reduce pressure in the portal vein system.
Study on the Effect of Carvedilol for Patients with Cirrhotic Portal Hypertension
This French trial evaluates how effective carvedilol, a beta-blocker medication, is in preventing digestive bleeding in patients with cirrhotic portal hypertension. The condition arises from liver cirrhosis and can lead to serious complications like bleeding from enlarged veins.
Main inclusion criteria: Patients must be 18 years or older with suspected cirrhotic portal hypertension meeting specific Baveno VII criteria. These include liver stiffness measurements combined with platelet counts, or the presence of high-risk gastroesophageal varices. Patients must not have had prior treatment with non-cardioselective beta-blockers and must be affiliated with social security.
Main exclusion criteria: The trial excludes patients outside the 18-65 age range, vulnerable populations, those with medical conditions other than cirrhotic portal hypertension, inability to take carvedilol, pregnancy or breastfeeding, current participation in another trial, allergies to similar medications, unstable severe heart conditions, severe kidney problems, and history of substance abuse.
Study focus: Participants take carvedilol 12.5 mg daily for approximately three months. The primary focus is measuring changes in the portosystemic gradient using endoscopic ultrasound after one month. The study also monitors for side effects and the occurrence of digestive bleeding over three months.
Investigational drug: Carvedilol is a non-selective beta-blocker with alpha-blocking activity that reduces blood pressure in the portal vein system, potentially lowering the risk of bleeding from enlarged veins.
Study on the Effects of Metformin in Patients with Cirrhosis and Portal Hypertension Already Treated with Carvedilol
This trial investigates whether adding metformin to existing carvedilol treatment can provide additional benefits in managing portal hypertension in patients with liver cirrhosis. Metformin is commonly used for diabetes management but is being explored for its potential liver-related benefits.
Main inclusion criteria: Patients must be at least 18 years old with a confirmed diagnosis of cirrhosis and high likelihood of having a hepatic venous pressure gradient of 12 mmHg or more. They must have been on a stable dose of at least 6.25 mg carvedilol daily for at least one month. The cause of cirrhosis must be stable for at least 6 months, and patients must have a Child-Pugh score of A or B.
Main exclusion criteria: The trial excludes patients with portal hypertension complications from cirrhosis who are not already on carvedilol treatment, and those with an HVPG less than 12 mmHg.
Study focus: Participants are randomly assigned to receive either metformin or placebo for 28 days while continuing their carvedilol treatment. The primary goal is to assess changes in the hepatic venous pressure gradient after this treatment period, with close monitoring throughout.
Investigational drugs: Metformin works by decreasing glucose production in the liver and improving insulin sensitivity, which may have beneficial effects on liver function. The study explores whether these effects can help reduce portal hypertension when added to carvedilol therapy.
Study on BI 685509 and Empagliflozin for Patients with Portal Hypertension in Compensated Cirrhosis
This large multi-country trial studies the experimental medication BI 685509, both alone and in combination with empagliflozin, in patients with compensated cirrhosis and portal hypertension. The trial spans nine European countries including Belgium, Italy, Austria, Germany, France, Spain, Netherlands, Denmark, and Romania.
Main inclusion criteria: Participants must be 18 to 75 years old with clinical signs of clinically significant portal hypertension, confirmed by gastroscopy showing enlarged veins or previous preventative treatment. They must have a baseline HVPG of 10 mmHg or more and diagnosed compensated cirrhosis due to hepatitis C, hepatitis B, or non-alcoholic steatohepatitis. Patients must be willing to undergo required pressure measurements and maintain stable doses of any concurrent medications like statins or beta-blockers.
Main exclusion criteria: The trial excludes patients with portal hypertension, compensated cirrhosis due to specific causes, type 2 diabetes, or those from vulnerable populations. The exclusion criteria appear to require clarification regarding which specific subtypes or conditions are excluded.
Study focus: The 8-week treatment period involves taking BI 685509 alone or combined with empagliflozin as oral tablets. The primary endpoint measures percentage change in HVPG from baseline, with secondary observations including significant HVPG reductions and monitoring for side effects like low blood pressure.
Investigational drugs: BI 685509 is an experimental medication targeting specific pathways to lower portal vein pressure. Empagliflozin, an SGLT2 inhibitor approved for diabetes management, helps the kidneys remove glucose and may have beneficial effects on blood pressure and liver health. The trial explores whether combining these medications provides enhanced benefits.
Study on the Effects of BI 685509 for Patients with Liver Cirrhosis and Portal Hypertension After First Decompensation Event
This trial investigates BI 685509 in patients with decompensated cirrhosis who have experienced their first major complication, such as bleeding from enlarged veins or fluid accumulation in the abdomen, and have since stabilized. The study takes place across Spain, France, Austria, Germany, and Romania.
Main inclusion criteria: Patients must be 18 to 75 years old with diagnosed cirrhosis due to non-cholestatic liver disease, including hepatitis C, hepatitis B, non-alcoholic fatty liver disease, alcohol-related disease, autoimmune hepatitis, Wilson’s disease, hemochromatosis, or alpha-1 antitrypsin deficiency. They must have had one previous significant decompensation event resolved at least 4 weeks before screening. Patients must be willing to undergo HVPG measurements and maintain stable doses of concurrent medications. Those with alcohol-related cirrhosis must have avoided alcohol for at least 2 months.
Main exclusion criteria: The trial excludes patients with other types of liver disease not related to non-cholestatic conditions, those without clinically significant portal hypertension or decompensated cirrhosis, patients not receiving standard care, those outside the specified age range, and vulnerable populations.
Study focus: This double-blind trial randomly assigns participants to receive BI 685509 or placebo for 8 weeks, with gradual dose increases to reach the target level. Regular monitoring tracks health status, occurrence of further complications, and side effects. The primary endpoint measures percentage change in HVPG from baseline to evaluate treatment effectiveness.
Investigational drug: BI 685509 is an experimental oral medication targeting specific pathways that influence blood flow and pressure in the liver. The trial assesses its safety and tolerability when added to standard care for patients with clinically significant portal hypertension following a decompensation event.
Summary
These six clinical trials represent diverse approaches to managing portal hypertension in patients with liver cirrhosis. The trials are concentrated primarily in Western European countries, with France, Austria, and Germany hosting multiple studies. Spain and Romania also participate in several trials, while Belgium, Italy, Netherlands, and Denmark contribute to at least one study each.
The investigational treatments span both repurposed existing medications and novel experimental compounds. Established drugs being studied include norfloxacin (antibiotic), telmisartan (blood pressure medication), carvedilol (beta-blocker), and metformin (diabetes medication). Two trials focus on the experimental drug BI 685509, either alone or combined with empagliflozin, representing the newest therapeutic approaches under investigation.
The trials address different stages of liver disease, from compensated cirrhosis where the liver still functions adequately, to decompensated cirrhosis with serious complications. Treatment durations vary from 28 days to 12 weeks, with all studies measuring changes in hepatic venous pressure gradient as a key outcome. This diverse portfolio of trials reflects ongoing efforts to find effective treatments for this serious condition across various patient populations and disease stages.
