* 1366-0021 P11 trial of BI 685509 for CSPH in compensated cirrhosis
Research type
Research Study
Full title
Randomised, double-blind, placebo-controlled and parallel group trial to investigate the effects of two doses (up-titration to a fixed dose regimen) of oral BI 685509 on portal hypertension after 24 weeks treatment in patients with clinically significant portal hypertension (CSPH) in compensated cirrhosis
IRAS ID
301764
Contact name
Stephen Ryder
Contact email
Sponsor organisation
Boehringer Ingelheim Ltd
Eudract number
2021-001285-38
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 10 months, 0 days
Research summary
Cirrhosis is a liver condition which can be caused by long-term consumption of alcohol that is above safe drinking limits. Cirrhosis can cause high blood pressure in the portal vein (the main blood vessel going into the liver). Currently, people with high blood pressure in the portal vein (Portal Hypertension) are treated with medicines to reduce their blood pressure. However, less than half of people treated in this way will benefit from their treatment. This study is funded by Boehringer Ingelheim. It will test whether two different doses of a drug called BI 685509, will help people with liver cirrhosis and high blood pressure in the portal vein. This drug is taken orally, in tablet form.
150 people with Portal Hypertension, caused by alcohol-related cirrhosis, will be randomised to receive either one of two doses of BI 685509, or a placebo (a pill with no active treatment in it). Participants will be recruited to the trial from the hospitals where they currently receive treatment. The study will be “blinded” so that neither the doctors, nor the participant will know which treatment they have been randomised to. Each participant will receive their treatment for 24 weeks, alongside their usual care, and will have a final follow-up visit 4 weeks after they finish the study treatment. The pressure in the portal vein will be measured at the beginning and end of the study, and compared between treatment groups to investigate the effects of the treatment.LAY SUMMARY OF STUDY RESULTS:
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 liver) This is a summary of results from 1 clinical study. This Lay Summary was developed with patients who were not involved in this clinical study.
We thank all study participants. You helped us to answer important questions about avenciguat and empagliflozin and the treatment of liver disease.What was this study about?
The purpose of this study was to find out whether 2 different doses of a medicine called avenciguat helps people with a type of liver disease called liver cirrhosis and high blood pressure in the portal vein (the main vessel going to the liver). Liver cirrhosis is the scarring of the liver caused by a wide range of conditions, such as viral hepatitis, fat accumulating in the liver, or drinking too much alcohol. Liver cirrhosis can be compensated, which means the liver is damaged and scarred but can still function.
The study was stopped early. This was because the sponsor decided to stop the clinical development of avenciguat for high blood pressure in the portal vein. The discontinuation was not related to any safety issues.Who took part in this study?
Men and women could take part in the study if they were aged between 18 and 75 years, had high blood pressure of 10 mmHg or more in the portal vein, with or without swollen veins in the oesophagus (tube that leads from the mouth to the stomach) or stomach, had received treatment for swollen veins in the oesophagus, had compensated liver cirrhosis caused by drinking too much alcohol and had no alcohol abuse or misuse for at least 2 months before the study.
80 people took part in this study. There were 58 men (72%) and 22 women (28%).
The youngest participant was 28 years old, and the oldest participant was 74 years old. The average age was 57 years.
Participants were from 2 different backgrounds: Asian (22%) and White (78%)How was this study done?
We wanted to find out whether 2 different doses of avenciguat reduce the blood pressure in the portal vein after 24 weeks of treatment.
80 participants were divided into 3 groups, randomly like drawing names from a hat. However, only 79 participants were treated. Every participant had an equal chance of being in each group. No one could choose which group a participant was placed in, because it was done with a computer. The groups were divided into low dose, high dose and placebo. Participants in the low dose group took 1 mg avenciguat twice a day for 1 week. Then, they took 2 mg avenciguat twice a day for the next 23 weeks. Participants in the high dose group took 1 mg avenciguat twice a day for 1 week. Then, they took 2 mg avenciguat twice a day for 1 week. After that, they took 3 mg avenciguat twice a day for the next 22 weeks. Participants in the placebo group took placebo twice a day for 24 weeks.
Avenciguat and placebo were taken as tablets. Dose was increased only if the lower dose was well tolerated.
Placebo tablets looked like avenciguat but did not contain any medicine. We compared avenciguat with placebo to find out how well avenciguat works. The participants continued to take their standard treatment during the study.
Participants and doctors did not know in which group the participants were. This is because knowing which treatment a participant gets might affect the results of the study. At the end of the study, researchers learned which treatment each participant took.
Participants visited the doctors regularly. During these visits, the doctors collected information about the participants’ health and noted any health problems. Participants were in the study for about 8 months.What were the results of this study?
After 24 weeks of treatment, both dose groups of avenciguat, when given in addition to the standard treatment, did not show an effect in reducing blood pressure in the portal vein in people with liver cirrhosis.Did participants have any unwanted effects in this study?
Yes, participants in all groups had unwanted effects. Unwanted effects are health problems that the doctors think were caused by the study medicine. In this study, 11 out of 54 participants (20%) in the avenciguat groups had unwanted effects. 7 out of 25 participants (28%) in the placebo group had unwanted effects.
The listing below shows the 3 most common unwanted effects in the avenciguat groups. The listing also shows how many participants in each group had each of these unwanted effects. There were 54 participants in the avenciguat group and 25 participants in the placebo group.
Dizziness: 3 participants of avenciguat group (6%), 0 participants of placebo group (0%)
Headache: 2 participants of avenciguat group (4%), 1 participant of placebo group (4%) Low blood pressure (Hypotension): 2 participants of avenciguat group (4%), 0 participants of placebo group (0%) Some unwanted effects in this study were serious because they required a stay in hospital (or if already in the hospital, they made the stay last longer), they were life-threatening and/or the doctor thought they were serious for any other reason.
In this study, 1 participant in the avenciguat group had a serious unwanted effect. 2 participants in the placebo group had serious unwanted effects. None of the unwanted effects occurred in more than 1 participant.Where did the study take place?
The following list shows the countries with the number of participants per country.
Romania (15), United States of America (13), China (7), Italy (7), Austria (5), Japan (5), Argentina (4), Spain (4), Korea (3), Canada (2), France (2), Germany (2), Taiwan (2), Belgium (1), Croatia (1), Denmark (1), Netherlands (1), Portugal (1), Singapore (1), Switzerland (1), United Kingdom (1).REC name
London - South East Research Ethics Committee
REC reference
21/FT/0135
Date of REC Opinion
20 Oct 2021
REC opinion
Further Information Favourable Opinion