Trial Outcomes & Findings for 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) (NCT NCT05161481)
NCT ID: NCT05161481
Last Updated: 2025-09-03
Results Overview
HVPG was calculated as the difference between the average wedged hepatic venous pressure (WHVP) and either: Proximal Free Hepatic Venous Pressure (PFHVP), if judged more reliable, or Average Free Hepatic Venous Pressure (FHVP), if considered more reliable. Based on the central reader's judgment: If PFHVP was more reliable: HVPG(mmHg)= Average WHVP (mmHg) - PFHVP (mmHg) If FHVP was more reliable: HVPG(mmHg)=Average WHVP (mmHg)-Average FHVP (mmHg) Percentage Change = (HVPG at 24 weeks- Baseline HVPG/Baseline HVPG) × 100 A restricted maximum likelihood (REML) approach using a mixed model with repeated measurements (MMRM) was used to estimate adjusted treatment means. The analysis included fixed categorical effects for treatment at each visit, use of non-selective beta-blockers (NSBBs) or carvedilol at baseline (yes/no), and fixed continuous effects for baseline hepatic venous pressure gradient (HVPG) at each visit.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
80 participants
Primary outcome timeframe
From first administration of trial medication up to 24 weeks.
Results posted on
2025-09-03
Participant Flow
This randomized, double-blind, placebo-controlled, parallel-group, multicenter trial included three treatment groups: two doses of avenciguat and a placebo, alongside standard care, in patients with clinically significant portal hypertension (CSPH) due to compensated alcohol-related cirrhosis. The primary objective was to estimate the mean difference in the percentage change in hepatic venous pressure gradient (HVPG) from baseline after 24 weeks. Safety and tolerability were also assessed.
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participant milestones
| Measure |
Placebo
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Overall Study
STARTED
|
26
|
27
|
27
|
|
Overall Study
Treated
|
25
|
27
|
27
|
|
Overall Study
COMPLETED
|
19
|
23
|
17
|
|
Overall Study
NOT COMPLETED
|
7
|
4
|
10
|
Reasons for withdrawal
| Measure |
Placebo
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Overall Study
Withdrawal of consent
|
0
|
1
|
1
|
|
Overall Study
Study terminated by sponsor
|
3
|
3
|
2
|
|
Overall Study
Adverse Event
|
3
|
0
|
6
|
|
Overall Study
Randomised in error and was not treated
|
1
|
0
|
0
|
|
Overall Study
Subject decision
|
0
|
0
|
1
|
Baseline Characteristics
Full analysis set (FAS) - this analysis set includes all randomised patients who received at least one dose of trial medication and have a baseline measurement for the primary endpoint recorded. The one participant wrongly randomized in the placebo group was not included in this set.
Baseline characteristics by cohort
| Measure |
Placebo
n=26 Participants
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
n=27 Participants
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
n=27 Participants
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
Total
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
57.8 Years
STANDARD_DEVIATION 8.1 • n=26 Participants
|
56.6 Years
STANDARD_DEVIATION 9.2 • n=27 Participants
|
57.1 Years
STANDARD_DEVIATION 10.9 • n=27 Participants
|
57.2 Years
STANDARD_DEVIATION 9.4 • n=80 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=26 Participants
|
9 Participants
n=27 Participants
|
4 Participants
n=27 Participants
|
22 Participants
n=80 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=26 Participants
|
18 Participants
n=27 Participants
|
23 Participants
n=27 Participants
|
58 Participants
n=80 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=26 Participants
|
9 Participants
n=27 Participants
|
3 Participants
n=27 Participants
|
16 Participants
n=80 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=26 Participants
|
18 Participants
n=27 Participants
|
24 Participants
n=27 Participants
|
64 Participants
n=80 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=26 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=80 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=26 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=80 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=26 Participants
|
6 Participants
n=27 Participants
|
6 Participants
n=27 Participants
|
18 Participants
n=80 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=26 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=80 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=26 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=80 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=26 Participants
|
21 Participants
n=27 Participants
|
21 Participants
n=27 Participants
|
62 Participants
n=80 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=26 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=80 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=26 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=80 Participants
|
|
Baseline hepatic venous pressure gradient (HVPG)
|
15.11 Millimeter mercury (mmHg)
STANDARD_DEVIATION 4.10 • n=25 Participants • Full analysis set (FAS) - this analysis set includes all randomised patients who received at least one dose of trial medication and have a baseline measurement for the primary endpoint recorded. The one participant wrongly randomized in the placebo group was not included in this set.
|
14.95 Millimeter mercury (mmHg)
STANDARD_DEVIATION 4.27 • n=27 Participants • Full analysis set (FAS) - this analysis set includes all randomised patients who received at least one dose of trial medication and have a baseline measurement for the primary endpoint recorded. The one participant wrongly randomized in the placebo group was not included in this set.
|
14.61 Millimeter mercury (mmHg)
STANDARD_DEVIATION 4.07 • n=27 Participants • Full analysis set (FAS) - this analysis set includes all randomised patients who received at least one dose of trial medication and have a baseline measurement for the primary endpoint recorded. The one participant wrongly randomized in the placebo group was not included in this set.
|
14.88 Millimeter mercury (mmHg)
STANDARD_DEVIATION 4.10 • n=79 Participants • Full analysis set (FAS) - this analysis set includes all randomised patients who received at least one dose of trial medication and have a baseline measurement for the primary endpoint recorded. The one participant wrongly randomized in the placebo group was not included in this set.
|
PRIMARY outcome
Timeframe: From first administration of trial medication up to 24 weeks.Population: Full analysis set (FAS) - this analysis set includes all randomised patients who received at least one dose of trial medication and have a baseline measurement for the primary endpoint recorded. The hypothetical strategy was used for handling intercurrent events for the primary objective as a main analysis as if all the intercurrent events had not happened.
HVPG was calculated as the difference between the average wedged hepatic venous pressure (WHVP) and either: Proximal Free Hepatic Venous Pressure (PFHVP), if judged more reliable, or Average Free Hepatic Venous Pressure (FHVP), if considered more reliable. Based on the central reader's judgment: If PFHVP was more reliable: HVPG(mmHg)= Average WHVP (mmHg) - PFHVP (mmHg) If FHVP was more reliable: HVPG(mmHg)=Average WHVP (mmHg)-Average FHVP (mmHg) Percentage Change = (HVPG at 24 weeks- Baseline HVPG/Baseline HVPG) × 100 A restricted maximum likelihood (REML) approach using a mixed model with repeated measurements (MMRM) was used to estimate adjusted treatment means. The analysis included fixed categorical effects for treatment at each visit, use of non-selective beta-blockers (NSBBs) or carvedilol at baseline (yes/no), and fixed continuous effects for baseline hepatic venous pressure gradient (HVPG) at each visit.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
n=27 Participants
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
n=27 Participants
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline After 24 Weeks of Treatment
|
7.07 Percentage of change
Interval -6.07 to 20.21
|
-1.33 Percentage of change
Interval -13.41 to 10.75
|
-7.11 Percentage of change
Interval -22.02 to 7.8
|
SECONDARY outcome
Timeframe: From first administration of trial medication up to 8 weeks.Population: Full analysis set (FAS) - this analysis set includes all randomised patients who received at least one dose of trial medication and have a baseline measurement for the primary endpoint recorded. All intercurrent events (ICEs) were handled using the treatment policy for the secondary endpoints. That is, all data collected after the intercurrent events will be included in the analysis.
HVPG was calculated as the difference between the average wedged hepatic venous pressure (WHVP) and either: Proximal Free Hepatic Venous Pressure (PFHVP), if judged more reliable. Average Free Hepatic Venous Pressure (FHVP), if considered more reliable. Based on the central reader's judgment: If PFHVP was more reliable: HVPG(mmHg)= Average WHVP (mmHg) - PFHVP (mmHg) If FHVP was more reliable: HVPG(mmHg)=Average WHVP (mmHg)-Average FHVP (mmHg) Percentage Change = (HVPG at 8 weeks- Baseline HVPG/Baseline HVPG) × 100 This endpoint was analyzed using the Treatment Policy Estimand and an ANCOVA model. The model included baseline HVPG as a linear covariate, and treatment and use of non-selective beta-blockers (NSBBs) or carvedilol as fixed effects.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
n=27 Participants
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
n=27 Participants
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline, Measured in Millimeters of Mercury (mmHg), After 8 Weeks of Treatment
|
-5.41 Percentage of change
Interval -14.3 to 3.47
|
-1.90 Percentage of change
Interval -10.62 to 6.82
|
-2.72 Percentage of change
Interval -13.03 to 7.59
|
SECONDARY outcome
Timeframe: From first administration of trial medication up to 8 weeks.Population: Full analysis set (FAS) - this analysis set includes all randomised patients who received at least one dose of trial medication and have a baseline measurement for the primary endpoint recorded. If a patient misses the Week 8 visit, the missing data was not imputed.
Response is defined as greater than 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatment. The number of participants with, or without response after 8 weeks of treatment with Avenciguat is reported.
Outcome measures
| Measure |
Placebo
n=24 Participants
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
n=25 Participants
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
n=18 Participants
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Response Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 8 Weeks of Treatment
Yes
|
10 Participants
|
10 Participants
|
7 Participants
|
|
Response Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 8 Weeks of Treatment
No
|
14 Participants
|
15 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: From first administration of trial medication up to 24 weeks.Population: Full analysis set (FAS) - this analysis set includes all randomised patients who received at least one dose of trial medication and have a baseline measurement for the primary endpoint recorded. If a patient misses the Week 24 visit, the missing data was not imputed.
Response is defined as greater than 10% reduction from baseline HVPG (measured in mmHg) after 24 weeks of treatment.
Outcome measures
| Measure |
Placebo
n=19 Participants
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
n=23 Participants
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
n=17 Participants
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Response Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 24 Weeks of Treatment
Yes
|
5 Participants
|
11 Participants
|
4 Participants
|
|
Response Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 24 Weeks of Treatment
No
|
14 Participants
|
12 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: From first administration of trial medication up to 24 weeks.Population: Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
A decompensation event is characterized by the occurrence of any of the following: * Ascites, * Variceal hemorrhage, * Overt hepatic encephalopathy.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
n=27 Participants
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
n=27 Participants
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Occurrence of One or More Decompensation Events (i.e. Ascites, VH, and / or Overt HE) During the 24 Week Treatment Period
|
2 Participants
|
0 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: From first administration of trial medication up to 8 weeks.Population: Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
The occurrence of CTCAE grade 3 (or higher) hypotension or syncope, based on the investigator's judgment, during the first 8 weeks of the treatment period is reported.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
n=27 Participants
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
n=27 Participants
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the First 8 Weeks of the Treatment Period
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From first administration of trial medication up to 24 weeks.Population: Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
The occurrence of CTCAE grade 3 (or higher) hypotension or syncope, based on the investigator's judgment, during the 24 weeks of the treatment period is reported.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
n=27 Participants
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
n=27 Participants
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the 24 Week Treatment Period
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From first administration of trial medication up to 8 weeks.Population: Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
The occurrence of hypotension or syncope during the first 8 weeks of the treatment period leading to the participant's discontinuation is reported.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
n=27 Participants
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
n=27 Participants
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Occurrence of Discontinuation Due to Hypotension or Syncope During the First 8 Weeks of the Treatment Period
|
0 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From first administration of trial medication up to 24 weeks.Population: Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
The occurrence of hypotension or syncope during the first 24 weeks of the treatment period leading to the participant's discontinuation is reported.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2 mg BID
n=27 Participants
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3 mg BID
n=27 Participants
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Occurrence of Discontinuation Due to Hypotension or Syncope During the 24 Week Treatment Period
|
0 Participants
|
0 Participants
|
1 Participants
|
Adverse Events
Placebo
Serious events: 4 serious events
Other events: 9 other events
Deaths: 0 deaths
Avenciguat 2mg BID
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Avenciguat 3mg BID
Serious events: 3 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=25 participants at risk
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2mg BID
n=27 participants at risk
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3mg BID
n=27 participants at risk
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
4.0%
1/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Gastrointestinal disorders
Ascites
|
4.0%
1/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Gastrointestinal disorders
Gastritis haemorrhagic
|
0.00%
0/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
3.7%
1/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
4.0%
1/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
3.7%
1/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
3.7%
1/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
4.0%
1/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
3.7%
1/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
3.7%
1/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
Other adverse events
| Measure |
Placebo
n=25 participants at risk
Participants in this dose group received matching placebo twice daily (BID) throughout the study period. At Visit 2 (Week 1), each dose consisted of one 1 mg placebo tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), a pseudo up-titration was implemented, maintaining the same tablets (one 1 mg and one 2 mg placebo per dose) for blinding. From Visit 4 onward (Week 3+), a second pseudo up-titration adjusted the dose to one 2 mg placebo tablet and one 3 mg placebo tablet per dose (four tablets daily). All doses were taken with water, with or without food.
|
Avenciguat 2mg BID
n=27 participants at risk
Participants received Avenciguat combined with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg Avenciguat tablet (four tablets daily)). From Visit 4 onward (Week 3+), a pseudo up-titration was applied, with participants taking one 2 mg Avenciguat tablet and one 3 mg placebo tablet per dose (four tablets daily) to maintain blinding. This regimen continued for 24 weeks, with doses taken with water, with or without food.
|
Avenciguat 3mg BID
n=27 participants at risk
Participants received Avenciguat with matching placebo tablets twice daily (BID). At Visit 2 (Week 1), each dose contained one 1 mg Avenciguat tablet and one 2 mg placebo tablet (four tablets daily). At Visit 3 (Week 2), the dose was up titrated to 2 mg Avenciguat BID (one 1 mg placebo tablet and one 2 mg active tablet (four tablets daily)). From Visit 4 onward (Week 3+), the dose was further up titrated to 3 mg Avenciguat BID (one 2 mg placebo tablet and one 3 mg active tablet per dose (four tablets daily)). This regimen was maintained for 24 weeks, with doses taken with water, with or without food.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
4.0%
1/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
7.4%
2/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Gastrointestinal disorders
Abdominal distension
|
4.0%
1/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
7.4%
2/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Gastrointestinal disorders
Constipation
|
8.0%
2/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
7.4%
2/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Infections and infestations
COVID-19
|
8.0%
2/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
3.7%
1/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
7.4%
2/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
7.4%
2/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
3.7%
1/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Infections and infestations
Upper respiratory tract infection
|
4.0%
1/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
7.4%
2/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Nervous system disorders
Dizziness
|
8.0%
2/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
11.1%
3/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Nervous system disorders
Headache
|
8.0%
2/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
7.4%
2/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.0%
2/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
3.7%
1/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Vascular disorders
Hypertension
|
8.0%
2/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
7.4%
2/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
7.4%
2/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
|
Vascular disorders
Hypotension
|
0.00%
0/25 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
0.00%
0/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
11.1%
3/27 • AE collection: From the first Avenciguat or placebo dose to the last dose, plus a 7-day residual effect period, totaling up to 182 days. All-cause mortality: From the first Avenciguat or placebo dose to the study's end, totaling up to 196 days.
Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER