Asymptomatic CirrhosisPhase 3CARVECIRNCT06263816
Effect of Long-term Carvedilol to Prevent Decompensation or Death in Patients With Asymptomatic Child-Pugh A5 to B8 Cirrhosis and Clinically Significant Portal Hypertension: a Multicenter Double-blind Randomized Control Trial
A Phase 3 study testing Experimental group: Patients will be treated with carvedilol. in people with Asymptomatic Cirrhosis and Clinically Significant Portal Hypertension, run by University Hospital, Tours at 24 sites in France.
Trial summary
Decompensation of cirrhosis is a turning point in cirrhosis course, as associated with a marked decrease in life expectancy. Thus, prevention of decompensation is crucial. The usefulness of carvedilol to prevent decompensation of cirrhosis in patients with TE-LSM ≥ 25 kPa as a surrogate marker for clinically… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asymptomatic Cirrhosis, Clinically Significant Portal Hypertension
- What is being tested?
- Experimental group: Patients will be treated with carvedilol.
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 290 participants
- Where
- 24 sitesFrance
- Study dates
- 17 Jun 2025to 17 Jul 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female≥ 18 years of age
- Cirrhosis related to hepatitis C or hepatitis B virus without viral replication for at least 2 years.
- Or Cirrhosis related to alcohol consumption (active or abstinent) Or Cirrhosis related to metabolic syndrome or cryptogenic with BMI < 30 kg/m2
- 2 TE-LSM (Fibroscan®) performed in fasting conditions, using either the M or the XL probe >=25 kPa, within 12 months before inclusion
- Absence of medium or large varices or small varices with red signs at endoscopy within 3 months before inclusion
- Child-Pugh A5 to B8
Show all 9Show fewer
- Affiliation to a French social security system.
- Written informed consent obtained from the participant or participant's legal representative
- For child-bearing aged women, contraception using oral contraceptive, or intrauterine device or mechanical contraception
Who cannot join
- History of overt ascites or encephalopathy <12 months before inclusion
- Treatment with either diuretics or lactulose or rifaximin <3 months before inclusion
- Any history of portal hypertension related bleeding
- Baseline heart rate <65/min or systolic blood pressure <100 mm Hg
- Previous transjugular intrahepatic portosystemic shunt (TIPSS) or liver transplantation
- Previous history or active hepatocellular carcinoma
Show all 25Show fewer
- Glomerular filtration rate (CKD-Epi) < 30 mL/min
- Strict indication to selective or nonselective beta-blockers: history of acute myocardial infarction, congestive heart failure
- Strict contraindication to selective or nonselective beta-blockers:
- decompensated congestive heart failure
- grade 2 or 3 atrioventricular block
- sinus node dysfunction without pacemaker
- severe asthma according to WHO classification [63]
- severe Chronic Obstructive Pulmonary Disease, defined stage 3 or 4 of the GOLD classification, i.e.FEV1<50% of the predicted value (https://goldcopd.org/)
- severe Raynaud disease, defined as repetitive episodes of biphasic colour (at least two) of pallor, cyanosis, erythema, in addition to paresthesia or numbness, occurring in both cold and normal environments [64].
- Known hypersensitivity to carvedilol
- Concomitant use of Cimétidin
- Concomitant use of class I antiarythmic agents (except lidocaïn) (i.e.cibenzoline, disopyramide, flécaïnide, hydroquinidine méxilétine, propafenone, quinidine)
- Concomitant use of calcium antagonists: diltiazem, vérapamil and bépridil
- Concomitant use of clonidine, méthyldopa, guanfacine, moxonidine, rilménidine
- Concomitant use of fingolimod
- Concomitant use of potent inhibitors (e.g. ketoconazole, HIV protease inhibitors) or inductors (e.g. rifampin, carbamazepine, phenytoin) of CYP3A4 (see appendix 7)
- Pregnancy or breastfeeding
- Non ability for participant to comply with the requirements of the study
- Life expectancy <12 months
Trial locations and contacts
24 sites in 1 country. Contact the study team or a site near you to ask about taking part.
24 sites in 1 country
France24 sites
CHU Amiens Picardie
Amiens
NGUYEN KHAC Eric, Dr, nguyen-khac.eric@chu-amiens.fr
CHU Angers
Angers
OBERTI FREDERIC, froberti@chu-angers.fr
CHU Beaujon
Assistance Publique Hôpitaux de Paris
RAUTOU PIERRE EMMANUEL, Dr, pierre-emmanuel.rautou@aphp.fr
CHU Jean Minjoz
Besançon
WEIL DELPHINE, Dr, dweil@chu-besancon.fr
CHU Haut Lévêque
Bordeaux
DE LEDINGHEN VICTOR, Dr, victor.deledinghen@chu-bordeaux.fr
CHU Caen
Caen
OLLIVIER-HOURMAND Isabelle, Dr, ollivierhourmand-i@chu-Caen.fr
CH intercommunal de Créteil
CH Intercommunal de Créteil
ROSA ISABELLE, dR, isabelle.rosa@chi-creteil.fr
CHU Clermont Ferrand
Clermont-Ferrand
ABERGEL ARMAND, Dr, aabergel@chu-clermontferrand.fr
Hôpital Henri Mondor
Créteil
LEROY Vincent, Dr, vincent.leroy2@aphp.fr
Hôpital Francois Mitterrand
Dijon
MINELLO Anne, Dr, anne.minello@chu-dijon.fr
CHU Grenoble
Grenoble
HILLERET Marie-Noelle, Dr, mnhilleret@chu-grenoble.fr
Centre Hospitalier départemental de Vendée
La Roche-sur-Yon
LAGIN Ludovic, Dr, ludovic.lagin@ght85.fr
Hôpital Huriez
Lille
LOUVET ALEXANDRE, Dr, alexandre.louvet@chru-lille.fr
CHU la Croix Rousse
Lyon
LEBOSSE FANNY, Dr, fanny.lebosse@chu-lyon.fr
CHU de Montpellier
Montpellier
URSIC Jose, Dr, jose.ursicbedoya@chu-montpellier.fr
CHU Hôtel Dieu
Nantes
ARCHAMBEAUD Isabelle, Dr, isabelle.archambeaud@chu-nantes.fr
CHU Avicenne
Paris
BLAISE LORAINE, Dr, lorraine.blaise@aphp.fr
CHU Pitié-Salpêtrière
Paris
THABUT DOMINIQUE, Dr, dominique.thabut@aphp.fr
CHU Saint-Antoin
Paris
OZENNE Violaine, Dr, violaine.ozenne@aphp.fr
CHU de Reims
Reims
BERNARD CHABERT Brigitte, Dr, bbernard-chabert@chu-reims.fr
CHU Pontchaillou
Rennes
JEZEQUIEL Caroline, Dr, caroline.jezequiel@chu-rennes.fr
Hôpitaux Universitaires de Strasbourg
Strasbourg
TRIPON Simona, Dr, simona.tripon@chru-strasbourg.fr
CHU de Toulouse
Toulouse
BUREAU Christophe, Dr, bureau.c@chu-toulouse.fr
Hôpital Paul Brousse
Villejuif
KOUNIS Ilias, Dr, ilias.kounis@aphp.fr
About this study
Decompensation of cirrhosis is a turning point in cirrhosis course, as associated with a marked decrease in life expectancy. Thus, prevention of decompensation is crucial.
The usefulness of carvedilol to prevent decompensation of cirrhosis in patients with TE-LSM ≥ 25 kPa as a surrogate marker for clinically significant portal hypertension, has never been evaluated in a clinical trial.
Read the detailed description
Decompensation of cirrhosis is a turning point in cirrhosis course, as associated with a marked decrease in life expectancy. Thus, prevention of decompensation is crucial.
Portal hypertension (PH) is the strongest predictor of decompensation. Hepatic venous pressure gradient (HVPG) is the reference standard for the evaluation of PH. HVPG ≥10 mm Hg, called "clinically significant portal hypertension", identifies a population with a high risk of decompensation. HVPG measurement is an invasive procedure, only routinely available in expert centers. Liver stiffness measurement (LSM) using transient elastography (TE) (referred as TE LSM) using Fibroscan can provide an indirect estimate of HVPG. TE-LSM ≥ 25 kPa can rule-in HVPG ≥10 mm Hg with a specificity >90%.
Nonselective beta-blockers (NSBBs) lower portal pressure by decreasing portal venous inflow. Carvedilol also decreases intrahepatic vascular resistance, and thereby achieves a greater reduction in portal pressure than propranolol. At low-dose (≤12.5 mg/day), carvedilol is safe in patients with compensated cirrhosis.
In patients with asymptomatic cirrhosis, NSBBs were recommended when medium or large varices (high-risk varices) are present for prophylaxis of variceal bleeding. In a recent randomized controlled trial, the PREDESCI study (NCT01059396), NSBBs reduced incidence of decompensation or death in patients with compensated cirrhosis with clinically significant portal hypertension. In the PREDESCI study, the diagnosis of clinically significant portal hypertension was based on invasive HVPG measurement, so that its results are not applicable in clinical practice.
The usefulness of carvedilol to prevent decompensation of cirrhosis in patients with TE-LSM ≥25 kPa as a surrogate marker for clinically significant portal hypertension, has never been evaluated in a randomized controlled trial.
- Being tested
- Experimental group: Patients will be treated with carvedilol., Control group: Patients will receive a placebo.
- Keywords
- carvedilol, decompensation, death, asymptomatic cirrhosis, significant portal hypertension
- Medical subject headings
- Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental group: Patients will be treated with carvedilol.Drug
Patients will receive the number of pills of carvedilol corresponding to the dose determined during the titration period (either one pill of 6.25 mg in the morning or 1 pill of 6.25 mg twice a day, 1 in the morning and 1 in the evening.
Control group: Patients will receive a placebo.Other
Patients will receive the number of pills of placebo corresponding to the dose determined during the titration period (either one pill in the morning or 1 pill twice a day: 1 in the morning and 1 in the evening).
| Study group | Role | What they receive |
|---|---|---|
| Carvédilol | Experimental | Not described Receives: Drug: Experimental group: Patients will be treated with carvedilol. |
| Placebo | Placebo comparator | Not described Receives: Other: Control group: Patients will receive a placebo. |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the effect of low dose carvedilol (<=12.5 mg per day) versus placebo on the occurrence of decompensation of cirrhosis or liver-related death at 36 months
Primary endpoint will be the occurrence, within 36 months after inclusion, of either decompensation of cirrhosis or liver-related death.
Decompensation of cirrhosis is defined as a composite endpoint including one event among: overt ascites, overt hepatic encephalopathy and variceal bleeding according to Baveno VII consensus conference [1].
Liver-related death is defined as death occurring in the context of complicated ascites (e.g. spontaneous bacterial peritonitis or acute kidney injury), encephalopathy, variceal hemorrhage, or ACLF
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2024
- Study start17 Jun 2025 (estimated)
- Primary completion17 Jul 2027 (estimated)
- Study completion17 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asymptomatic CirrhosisStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study will be a national multicentric, phase III, superiority double-blinded randomized controlled trial with two parallel arms: carvedilol versus placebo. The primary end-point will be assessed by the local investigator (hepatologist), blinded of the randomization arm
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 290 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Collaborators
- Centre Hospitalier Universitaire Amiens Picardie, University Hospital, Angers, Assistance Publique Hopitaux Paris BEAUJON, Centre Hospitalier Universitaire de Caen, Centre Hospitalier intercommunal de Créteil, Hospices Civils de Lyon, Centre Hospitalier Universitaire Grenoble, Centre Hospitalier Universitaire Haut Lévêque, Centre Hospitalier Régional Universitaire Lille, Centre Hospitalier Universitaire Jean Minjoz, Assistance Publique Hopitaux Paris AVICENNE, Centre Hospitalier Universitaire Clermont Ferrand, Groupe Hospitalier Pitie-Salpetriere, Centre Hospitalier Universitaire Pontchaillou, Assistance Publique Hopitaux Paris ST ANTOINE, Assistance Publique Hopitaux Paris PAUL BROUSSE, University Hospital, Montpellier, Assistance Publique Hopitaux Paris HENRI MONDOR, Centre Hospitaliser Départemental de Vendée, Nantes University Hospital, Centre Hospitalier Universitaire Dijon, CHU de Reims, Hôpitaux Universitaires de Strasbourg, University Hospital, Toulouse
- Responsible party
- Sponsor
- Investigators
- Laure ELKRIEF, MD-PhD, Study director, University Hospital, Tours
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06263816
- Sponsor's protocol ID
- CARVECIR
- Acronym
- CARVECIR
- Status last verified
- Jun 2025
- First submitted
- 8 Feb 2024
- Last updated
- 4 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Long-term Carvedilol to Prevent Decompensation or Death in Patients With Asymptomatic Child-Pugh A5 to B8 Cirrhosis and Clinically Significant Portal Hypertension: a Multicenter Double-blind Randomized Control Trial
- ClinicalTrials.gov ID
- NCT06263816
- Acronym / sponsor ID
- CARVECIR / CARVECIR
- Keywords
- carvedilol, decompensation, death, asymptomatic cirrhosis, significant portal hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 290 participants (estimated)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Collaborators
- Centre Hospitalier Universitaire Amiens Picardie, University Hospital, Angers, Assistance Publique Hopitaux Paris BEAUJON, Centre Hospitalier Universitaire de Caen, Centre Hospitalier intercommunal de Créteil, Hospices Civils de Lyon, Centre Hospitalier Universitaire Grenoble, Centre Hospitalier Universitaire Haut Lévêque, Centre Hospitalier Régional Universitaire Lille, Centre Hospitalier Universitaire Jean Minjoz, Assistance Publique Hopitaux Paris AVICENNE, Centre Hospitalier Universitaire Clermont Ferrand, Groupe Hospitalier Pitie-Salpetriere, Centre Hospitalier Universitaire Pontchaillou, Assistance Publique Hopitaux Paris ST ANTOINE, Assistance Publique Hopitaux Paris PAUL BROUSSE, University Hospital, Montpellier, Assistance Publique Hopitaux Paris HENRI MONDOR, Centre Hospitaliser Départemental de Vendée, Nantes University Hospital, Centre Hospitalier Universitaire Dijon, CHU de Reims, Hôpitaux Universitaires de Strasbourg, University Hospital, Toulouse
- Study start
- 17 Jun 2025 (estimated)
- Primary completion
- 17 Jul 2027 (estimated)
- Study completion
- 17 Jul 2030 (estimated)
- First posted
- 16 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Decompensation of cirrhosis is a turning point in cirrhosis course, as associated with a marked decrease in life expectancy. Thus, prevention of decompensation is crucial.
The usefulness of carvedilol to prevent decompensation of cirrhosis in patients with TE-LSM ≥ 25 kPa as a surrogate marker for clinically significant portal hypertension, has never been evaluated in a clinical trial.
Detailed description
Decompensation of cirrhosis is a turning point in cirrhosis course, as associated with a marked decrease in life expectancy. Thus, prevention of decompensation is crucial.
Portal hypertension (PH) is the strongest predictor of decompensation. Hepatic venous pressure gradient (HVPG) is the reference standard for the evaluation of PH. HVPG ≥10 mm Hg, called "clinically significant portal hypertension", identifies a population with a high risk of decompensation. HVPG measurement is an invasive procedure, only routinely available in expert centers. Liver stiffness measurement (LSM) using transient elastography (TE) (referred as TE LSM) using Fibroscan can provide an indirect estimate of HVPG. TE-LSM ≥ 25 kPa can rule-in HVPG ≥10 mm Hg with a specificity >90%.
Nonselective beta-blockers (NSBBs) lower portal pressure by decreasing portal venous inflow. Carvedilol also decreases intrahepatic vascular resistance, and thereby achieves a greater reduction in portal pressure than propranolol. At low-dose (≤12.5 mg/day), carvedilol is safe in patients with compensated cirrhosis.
In patients with asymptomatic cirrhosis, NSBBs were recommended when medium or large varices (high-risk varices) are present for prophylaxis of variceal bleeding. In a recent randomized controlled trial, the PREDESCI study (NCT01059396), NSBBs reduced incidence of decompensation or death in patients with compensated cirrhosis with clinically significant portal hypertension. In the PREDESCI study, the diagnosis of clinically significant portal hypertension was based on invasive HVPG measurement, so that its results are not applicable in clinical practice.
The usefulness of carvedilol to prevent decompensation of cirrhosis in patients with TE-LSM ≥25 kPa as a surrogate marker for clinically significant portal hypertension, has never been evaluated in a randomized controlled trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This study will be a national multicentric, phase III, superiority double-blinded randomized controlled trial with two parallel arms: carvedilol versus placebo. The primary end-point will be assessed by the local investigator (hepatologist), blinded of the randomization arm
| Arm | Type | Receives |
|---|---|---|
| Carvédilol | Experimental | Drug: Experimental group: Patients will be treated with carvedilol. |
| Placebo | Placebo comparator | Other: Control group: Patients will receive a placebo. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female≥ 18 years of age
- Cirrhosis related to hepatitis C or hepatitis B virus without viral replication for at least 2 years.
- Or Cirrhosis related to alcohol consumption (active or abstinent) Or Cirrhosis related to metabolic syndrome or cryptogenic with BMI < 30 kg/m2
- 2 TE-LSM (Fibroscan®) performed in fasting conditions, using either the M or the XL probe >=25 kPa, within 12 months before inclusion
- Absence of medium or large varices or small varices with red signs at endoscopy within 3 months before inclusion
Key exclusion criteria (25 listed)
- History of overt ascites or encephalopathy <12 months before inclusion
- Treatment with either diuretics or lactulose or rifaximin <3 months before inclusion
- Any history of portal hypertension related bleeding
- Baseline heart rate <65/min or systolic blood pressure <100 mm Hg
- Previous transjugular intrahepatic portosystemic shunt (TIPSS) or liver transplantation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Experimental group: Patients will be treated with carvedilol.Patients will receive the number of pills of carvedilol corresponding to the dose determined during the titration period (either one pill of 6.25 mg in the morning or 1 pill of 6.25 mg twice a day, 1 in the morning and 1 in the evening. | Drug | Carvédilol |
| Control group: Patients will receive a placebo.Patients will receive the number of pills of placebo corresponding to the dose determined during the titration period (either one pill in the morning or 1 pill twice a day: 1 in the morning and 1 in the evening). | Other | Placebo |
Primary outcome
To evaluate the effect of low dose carvedilol (<=12.5 mg per day) versus placebo on the occurrence of decompensation of cirrhosis or liver-related death at 36 months
Time frame: 36 months
Primary endpoint will be the occurrence, within 36 months after inclusion, of either decompensation of cirrhosis or liver-related death. Decompensation of cirrhosis is defined as a composite endpoint including one event among: overt ascites, overt hepatic encephalopathy and variceal bleeding according to Baveno VII consensus conference [1]. Liver-related death is defined as death occurring in the context of complicated ascites (e.g. spontaneous bacterial peritonitis or acute kidney injury), encephalopathy, variceal hemorrhage, or ACLF
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2025.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Laure ELKRIEF, MD-PhD study director
University Hospital, Tours
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Experimental group: Patients will be treated with carvedilol. in people with Asymptomatic Cirrhosis and Clinically Significant Portal Hypertension, run by University Hospital, Tours at 24 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Laure ELKRIEF, MD-PhD (+33 247475965, l.elkrief@chu-tours.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the effect of low dose carvedilol (<=12.5 mg per day) versus placebo on the occurrence of decompensation of cirrhosis or liver-related death at 36 months (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2025.