CARPEUS : Effect of Carvedilol on the Portosystemic Gradient as Measured by Endoscopic Ultrasound (CARPEUS)

The purpose of this study is to assess the efficacy after one month of treatment with Carvedilol (12.5 mg daily) in primary prophylaxis of digestive haemorrhage due to portal hypertension in cirrhosis, by endoscopic ultrasound-guided portal pressure gradient measurement.

Study Overview

• Status: Recruiting
• Conditions: Cirrhosis; Portal Hypertension Related to Cirrhosis
• Intervention / Treatment: Drug: Carvedilol

Detailed Description

After being informed about the study and potential risks, all patients giving written informed consent will undergo a screening period to determine eligibility for entry study.

- Inclusion visit (day 1) includes an oesogastroduodenal fibroscopy (OGDF) followed by an endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) measurement, an electrocardiogram, a clinical examination, and a first intake of study treatment : Carvedilol 3.125 mg.

Carvedilol, day 2 to day 8: 6.25 mg/day (3.125 mg twice a day). - Visit 2 (day 6 +/- 2 days): clinical examination, record of potential adverse events, vital signs (arterial pressure, pulse rate), electrocardiogram if indicated, assessment of compliance with study treatment.

Carvedilol, day 9 to day 90 (end of study visit): 12.5 mg/day (6.25 mg twice a day).

- Visit 3 (day 13 +/- 2 days): clinical examination, record of potential adverse events, vital signs (arterial pressure, pulse rate), electrocardiogram if indicated, assessment of compliance with study treatment.

Carvedilol will be continued at the dose of 12.5 mg/day, on a long-term basis. - Visit 4 (day 30-45): OGDF followed by an EUS-PPG measurement, clinical examination, record of potential adverse events, vital signs (arterial pressure, pulse rate), electrocardiogram if indicated, assessment of compliance with study treatment.

Carvedilol will be continued at the dose of 12.5 mg/day.

- Visit 5 (day 90 +/- 7 jours), end of study visit: clinical examination, record of potential adverse events, vital signs (arterial pressure, pulse rate), electrocardiogram, assessment of compliance with study treatment.

Treatment with Carvedilol will be prescribed by a cardiologist and continued at the dose of 12.5 mg/day.

Follow-up of the patient according to standard practice. NB: an adaptation of the dose of Carvedilol may be considered according to tolerability, throughout the study.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lise LACLAUTRE; Phone Number: +33473754963; Email: promo_internet_drci@chu-clermontferrand.fr

Study Locations

• France
  • Clermont-Ferrand, France, 63000
    • Not yet recruiting
    • Lise Laclautre
    • Principal Investigator: Armando ABERGEL
  • Clermont-Ferrand, France, 63003
    • Recruiting
    • Chu Estaing Medecine Digestive Et Hepatobiliaire
    • Contact: Armando ABERGEL; Phone Number: +33473750523; Email: aabergel@chu-clermontferrand.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients ≥ 18 years

• Suspected portal hypertension associated with cirrhosis (of any aetiology) as defined by:

  1. Baveno VII criteria :

     Liver stiffness ≥ 25 kPa Or Liver stiffness between 20 and 25 kPa and platelets < 150 G/L Or Liver stiffness between 15 and 20 kPa and platelets < 110 G/L Or Liver stiffness > 20 kPa and/or platelets < 150 G/L in patients with cirrhosis due to NASH

     Or Oesophageal varices with high risk of bleeding :

     Size > 5 mm (stage 2 or 3) Or Size ≤ 5 mm and red spots Or Size ≤ 5 mm and Child-Pugh score C

  2. and/or the presence of a radiological sign of portal hypertension : Portosystemic shunts: rectal varices, splenorenal shunts, repermeabilization of the umbilical vein.
  3. and/or splenic elasticity > 50 kPa.
• Patients naive to treatment with cardioselective beta blockers
• Affiliated to french health insurance system

Exclusion Criteria:

• Absolute contraindications to beta blockers :

  • hypersensitivity to the active substance (carvedilol) or to any of the excipients listed in section 6.1 of the summary of product characteristics
  • patients with severe decompensated heart failure, with signs of fluid overload (oedema, ascites, pulmonary stasis rales), and/or requiring treatment with a positive inotrope or venous vasodilator
  • second and third-degree atrioventricular blocks (unless presence of a permanent pacemaker)
  • severe bradycardia (≤ 50 bpm)
  • cardiac sinus disease (including sino-auricular block)
  • severe hypotension (systolic pressure < 85 mm Hg)
  • cardiogenic shock
  • severe asthma, severe chronic obstructive pulmonary disease, history of severe bronchospasm
  • history of anaphylactic reaction
  • Raynaud's phenomenon
  • peripheral circulatory disorder: severe obliterative arterial disease of the lower limbs
  • association with cimetidine
  • association with class I antiarrhythmics except lidocaine
  • pulmonary arterial hypertension
• Presence of severe acute alcoholic hepatitis (Madrey score ≥ 32).
• Current hepatic encephalopathy ≥ Grade 2.
• Ongoing hepato-renal syndrome.
• Profuse clinical ascites (only if it interferes with the feasibility of echo-endoscopy).
• History of oesophageal varices rupture.
• Hepatocellular carcinoma active or in remission for less than six months.
• Active or resolved portal vein thrombosis for less than six months.
• History of digestive surgery that does not allow the porto-systemic gradient to be measured using echo-endoscopy (gastrectomy, by-pass, etc.).
• Patients taking antiaggregants (except acetylsalicylic acid) or anticoagulants for embologenic CA/FA.
• Severe stage 4 chronic renal insufficiency or stage 5 end-stage renal insufficiency (clearance < 30 mL/min).

• Pregnant or breast-feeding women, or those planning to become pregnant*.

  *A pregnancy test will be carried out for women of childbearing potential, and the investigator will ensure that effective contraception is in place while Carvedilol is being taken and for 5 half-lives after stopping it.

• Patients protected by law (under guardianship, curatorship or safeguard of justice) or deprived of their freedom.
• Patients currently taking part in another clinical research protocol.
• Patients who do not understand French language.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single arm; All patients will receive Carvedilol per os (dose escalation up to 12.5 mg per day).

Drug: Carvedilol; Carvedilol per os, day 1:3.125 mg once, day 2 to day 8: 6.25 mg/day (3.125 mg twice a day), day 9 to day 90 (end of study visit): 12.5 mg/day (6.25 mg twice a day). After the end of the study, treatment with Carvedilol will be prescribed by a cardiologist and continued at the dose of 12.5 mg/day. The follow-up of the patient will be then done according to the standard practice.; Other Names: CARVEDILOL ARROW ® 6,25 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with a reduction of at least 10% in the porto-systemic gradient	Hemodynamic response (binary efficacy criterion), defined as a reduction of at least 10% in the echo-endoscopic portosystemic gradient compared with the baseline value measured at inclusion.	One month after starting carvedilol.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side-effects of beta blockers	Side effects of beta-blockers among the top ten reported in the literature, and percentage of patients discontinuing treatment due to side effects.	From enrollment to D90.
Number of participants with digestive hemorrhage	Digestive hemorrhage due to rupture of esophageal or gastric varices.	Within three months of starting Carvedilol.

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Investigators: Principal Investigator: Armando Abergel, University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: February 19, 2025
• First Submitted That Met QC Criteria: February 28, 2025
• First Posted (Actual): March 6, 2025

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Carvedilol.; Portal hypertension in cirrhosis.; EUS-PPG measurement.
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Fibrosis; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amines; Indoles; Alcohols; Propanolamines; Amino Alcohols; Propanols; Heterocyclic Compounds, 3-Ring; Carbazoles; Carvedilol
• Other Study ID Numbers: AOI 2023 POINCLOUX; 2024-518302-41-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No