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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-001285-38 | EudraCT Number |
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This study is open to adults with liver cirrhosis and high blood pressure in the portal vein (main vessel going to the liver). The purpose of this study is to find out whether a medicine called Avenciguat helps people with this condition.
Participants are put into 3 groups randomly, which means by chance. Participants in 2 groups take different doses of Avenciguat as tablets twice a day. Participants in the placebo group take placebo as tablets twice a day. Placebo tablets look like Avenciguat tablets but do not contain any medicine.
Participants are in the study for about 8 months. During this time, they visit the study site about 14 times. At 3 of the visits, the doctors check the pressure in a liver vein. This is done with a catheter (a long thin tube) and gives information about the pressure in the portal vein. The change in blood pressure is then compared between the groups to see whether the treatment works.
The doctors also regularly check participants' health and take note of any unwanted effects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Avenciguat 2 mg BID | Experimental | 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. |
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| Avenciguat 3 mg BID | Experimental | 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. |
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| Placebo | Placebo Comparator | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Avenciguat (BI 685509) | Drug | Participants received Avenciguat twice daily (BID) throughout the study. Up-titration depended on the assigned dose group. At Visit 2 (Week 1), each dose included one 1 mg Avenciguat tablet. At Visit 3 (Week 2), the dose was increased to one 2 mg Avenciguat tablet per dose. From Visit 4 onward (Week 3+), participants received one 3 mg Avenciguat tablet per dose. This regimen continued for 24 weeks, with all doses taken with water, with or without food. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline After 24 Weeks of Treatment | 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. | From first administration of trial medication up to 24 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline, Measured in Millimeters of Mercury (mmHg), After 8 Weeks of Treatment | 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. |
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Inclusion Criteria:
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
Clinical signs of Clinically Significant Portal Hypertension (CSPH) as described by either one of the points below. Each trial patient must have a gastroscopy during the screening period or within 6 months prior to screening.
CSPH defined as baseline Hepatic Venous Pressure Gradient (HVPG) ≥ 10 mmHg, based on a local interpretation of the pressure tracing
Diagnosis of compensated alcohol-related cirrhosis. Diagnosis must be based on histology (historical data is acceptable) or on clinical evidence of cirrhosis (e.g. platelet count < 150 x 10^9/L [150 x 10^3/µL], nodular liver surface on imaging or splenomegaly)
Abstinence from significant alcohol misuse / abuse for a minimum of 2 months prior to screening, and the ability to abstain from alcohol throughout the trial (both evaluated based on Investigator judgement)
Willing and able to undergo HVPG measurements per protocol (based on Investigator judgement)
If receiving statins must be on a stable dose for at least 3 months prior to screening, with no planned dose change throughout the trial Further inclusion criteria apply.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| California Liver Research Institute | Pasadena | California | 91105 | United States | ||
| Inland Empire Clinical Trials, LLC |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37095557 | Derived | Reiberger T, Berzigotti A, Trebicka J, Ertle J, Gashaw I, Swallow R, Tomisser A. The rationale and study design of two phase II trials examining the effects of BI 685,509, a soluble guanylyl cyclase activator, on clinically significant portal hypertension in patients with compensated cirrhosis. Trials. 2023 Apr 24;24(1):293. doi: 10.1186/s13063-023-07291-3. |
| Label | URL |
|---|---|
| Related Info | View source |
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Once the time frame criteria given under number 4 are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".
Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.
After structured results have been posted, all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 2, 2023 | Apr 15, 2025 |
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| Placebo matching Avenciguat (BI 685509) | Drug | Participants received matching placebo twice daily (BID) throughout the study. At Visit 2 (Week 1), each dose included one 1 mg and one 2 mg placebo tablet (four tablets daily). A pseudo up-titration was applied at Visit 3 (Week 2), maintaining the same tablet composition to preserve blinding. From Visit 4 (Week 3) onward, a second pseudo up-titration adjusted each dose to one 2 mg and one 3 mg placebo tablet (four tablets daily). All doses were taken with water, with or without food. |
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| From first administration of trial medication up to 8 weeks. |
| Response Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 8 Weeks of Treatment | 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. | From first administration of trial medication up to 8 weeks. |
| Response Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 24 Weeks of Treatment | Response is defined as greater than 10% reduction from baseline HVPG (measured in mmHg) after 24 weeks of treatment. | From first administration of trial medication up to 24 weeks. |
| Occurrence of One or More Decompensation Events (i.e. Ascites, VH, and / or Overt HE) During the 24 Week Treatment Period | A decompensation event is characterized by the occurrence of any of the following:
| From first administration of trial medication up to 24 weeks. |
| Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the First 8 Weeks of the Treatment Period | 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. | From first administration of trial medication up to 8 weeks. |
| Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the 24 Week Treatment Period | 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. | From first administration of trial medication up to 24 weeks. |
| Occurrence of Discontinuation Due to Hypotension or Syncope During the First 8 Weeks of the Treatment Period | The occurrence of hypotension or syncope during the first 8 weeks of the treatment period leading to the participant's discontinuation is reported. | From first administration of trial medication up to 8 weeks. |
| Occurrence of Discontinuation Due to Hypotension or Syncope During the 24 Week Treatment Period | The occurrence of hypotension or syncope during the first 24 weeks of the treatment period leading to the participant's discontinuation is reported. | From first administration of trial medication up to 24 weeks. |
| Rialto |
| California |
| 92377 |
| United States |
| Floridian Clinical Research-Miami Lakes-68368 | Miami Lakes | Florida | 33016 | United States |
| Northwell Health Center for Liver Disease | Manhasset | New York | 11030 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| American Research Corporation at the Texas Liver Institute | San Antonio | Texas | 78215 | United States |
| Hospital Italiano de Buenos Aires | CABA | C1199ABB | Argentina |
| Medical University of Innsbruck | Innsbruck | 6020 | Austria |
| AKH - Medical University of Vienna | Vienna | 1090 | Austria |
| Edegem - UNIV UZ Antwerpen | Edegem | 2650 | Belgium |
| Centre Hospitalier de l'Universite de Montreal (CHUM) | Montreal | Quebec | H2X 0A9 | Canada |
| Beijing Friendship Hospital | Beijing | 100050 | China |
| Beijing Youan Hospital, Capital Medical University | Beijing | 100071 | China |
| NanFang Hosptial | Guangzhou | 510515 | China |
| The Affiliated Hospital of Hangzhou Normal University | Hangzhou | 310000 | China |
| University Hospital Dubrava | Zagreb | 10000 | Croatia |
| Hvidovre Hospital | Hvidovre | 2650 | Denmark |
| HOP d'Angers | Angers | 49933 | France |
| HOP Rangueil | Toulouse | 31059 | France |
| Universitätsmedizin der Johannes Gutenberg-Universität Mainz | Mainz | 55131 | Germany |
| Universitätsklinikum Münster | Münster | 48149 | Germany |
| St. Josefs-Hospital, Wiesbaden | Wiesbaden | 65189 | Germany |
| Western Galilee Hospital | Nahariya | 2210001 | Israel |
| ASST Grande Ospedale Metropolitano Niguarda | Milan | 20162 | Italy |
| Azienda Ospedaliera Policlinico di Modena | Modena | 41124 | Italy |
| Policlinico "Paolo Giaccone" | Palermo | 90127 | Italy |
| Fondazione Policlinico Universitario A. Gemelli IRCCS | Roma | 00195 | Italy |
| Shin-yurigaoka General Hospital | Kanagawa, Kawasaki | 215-0026 | Japan |
| Kitasato University Hospital | Kanagawa, Sagamihara | 252-0375 | Japan |
| Yokohama City University Hospital | Kanagawa, Yokohama | 236-0004 | Japan |
| National Hospital Organization Yokohama Medical Center | Kanagawa, Yokohama | 245-8575 | Japan |
| Osaka Metropolitan University Hospital | Osaka, Osaka | 545-8586 | Japan |
| Leids Universitair Medisch Centrum (LUMC) | Leiden | 2333 ZA | Netherlands |
| ULS de Santa Maria, E.P.E | Lisbon | 1649-035 | Portugal |
| Regional Institute of Gastroenterology Hepatology "Prof. Dr. O. Fodor" | Cluj-Napoca | 400000 | Romania |
| Singapore General Hospital | Singapore | 169608 | Singapore |
| Soon Chun Hyang University Hospital Bucheon | Bucheon-si, Gyeonggi-do | 14584 | South Korea |
| Yonsei University Wonju Severance Christian Hospital | Wonju-si, Gangwon State | 26426 | South Korea |
| Hospital Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Ramón y Cajal | Madrid | 28034 | Spain |
| Hospital Puerta de Hierro | Majadahonda | 28222 | Spain |
| Ospedale Regionale di Lugano | Viganello | 6962 | Switzerland |
| Taipei Veterans General Hospital | Taipei | 11217 | Taiwan |
| Queen Elizabeth Hospital Birmingham | Birmingham | B15 2TH | United Kingdom |
| St Mary's Hospital | London | W2 1NY | United Kingdom |
| FG001 | 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. |
| FG002 | 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. |
| Treated |
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| COMPLETED | Completed trial medication |
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| NOT COMPLETED |
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Randomised set (RS) - this analysis set includes all enrolled patients that were randomised to the trial medication. One patient in the placebo group was randomised in error and was not treated.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Baseline hepatic venous pressure gradient (HVPG) | Mean hepatic venous pressure gradient (HVPG) at baseline. | 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. | Mean | Standard Deviation | Millimeter mercury (mmHg) |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline After 24 Weeks of Treatment | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Percentage of change | From first administration of trial medication up to 24 weeks. |
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| Secondary | Percentage Change in Hepatic Venous Pressure Gradient (HVPG) From Baseline, Measured in Millimeters of Mercury (mmHg), After 8 Weeks of Treatment | 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | Percentage of change | From first administration of trial medication up to 8 weeks. |
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| Secondary | Response Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 8 Weeks of Treatment | 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. | 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. | Posted | Count of Participants | Participants | From first administration of trial medication up to 8 weeks. |
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| Secondary | Response Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 24 Weeks of Treatment | Response is defined as greater than 10% reduction from baseline HVPG (measured in mmHg) after 24 weeks of treatment. | 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. | Posted | Count of Participants | Participants | From first administration of trial medication up to 24 weeks. |
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| Secondary | Occurrence of One or More Decompensation Events (i.e. Ascites, VH, and / or Overt HE) During the 24 Week Treatment Period | A decompensation event is characterized by the occurrence of any of the following:
| Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose. | Posted | Count of Participants | Participants | From first administration of trial medication up to 24 weeks. |
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| Secondary | Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the First 8 Weeks of the Treatment Period | 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. | Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose. | Posted | Count of Participants | Participants | From first administration of trial medication up to 8 weeks. |
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| Secondary | Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the 24 Week Treatment Period | 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. | Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose. | Posted | Count of Participants | Participants | From first administration of trial medication up to 24 weeks. |
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| Secondary | Occurrence of Discontinuation Due to Hypotension or Syncope During the First 8 Weeks of the Treatment Period | The occurrence of hypotension or syncope during the first 8 weeks of the treatment period leading to the participant's discontinuation is reported. | Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose. | Posted | Count of Participants | Participants | From first administration of trial medication up to 8 weeks. |
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| Secondary | Occurrence of Discontinuation Due to Hypotension or Syncope During the 24 Week Treatment Period | The occurrence of hypotension or syncope during the first 24 weeks of the treatment period leading to the participant's discontinuation is reported. | Treated set (TS) - the treated set includes all patients who were randomised to the trial medication and were treated with at least one dose. | Posted | Count of Participants | Participants | From first administration of trial medication up to 24 weeks. |
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 25 | 4 | 25 | 9 | 25 |
| EG001 | Avenciguat 2mg 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. | 0 | 27 | 1 | 27 | 10 | 27 |
| EG002 | Avenciguat 3mg 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. | 0 | 27 | 3 | 27 | 11 | 27 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 27.0 | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Gastritis haemorrhagic | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Oesophageal varices haemorrhage | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Hepatic enzyme increased | Investigations | MedDRA 27.0 | Systematic Assessment |
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| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
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| Hepatic encephalopathy | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA 27.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 27.0 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 27.0 | Systematic Assessment |
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This trial was discontinued after Boehringer Ingelheim ended Avenciguat's clinical development for CSPH due to lack of efficacy, not safety concerns. Enrollment was complete, but some patients were still in treatment. These patients were asked to stop trial medication and attend an Early Discontinuation Visit, then entered the follow-up period per the clinical trial protocol.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 018002430127 | clintriage.rdg@boehringer-ingelheim.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 12, 2024 | Apr 15, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D006975 | Hypertension, Portal |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
Not provided
Not provided
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| Model includes baseline HVPG as linear covariate and treatment and use of NSBBs or carvedilol as fixed effects, treatment by visit interaction and baseline HVPG by visit interaction. The following covariance structure has been used to fit the mixed model: Unstructured. | Difference of adjusted means | -14.18 | Standard Error of the Mean | 9.93 | 2-Sided | 95 | -34.09 | 5.72 | Other | The adjusted mean values for percentage change at Week 24 are derived for each group using the MMRM. The mean difference for the "Comparison vs Placebo," is the adjusted mean of the treatment group subtracted from the adjusted mean of the placebo group. |
| OG001 | 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. |
| OG002 | 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. |
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| OG002 | 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. |
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| OG002 | 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. |
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| OG002 | 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. |
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| OG002 | 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. |
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| OG002 | 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. |
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| OG002 | 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. |
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| OG002 | 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. |
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