RecruitingNot ApplicableNCT06861075

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

Sponsor

University Hospital, Clermont-Ferrand

Enrollment

30 participants

Start Date

Apr 16, 2025

Study Type

INTERVENTIONAL

Conditions

Cirrhosis Portal Hypertension Related to Cirrhosis

Summary

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria10

Patients ≥ 18 years
Suspected portal hypertension associated with cirrhosis (of any aetiology) as defined by:
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
and/or the presence of a radiological sign of portal hypertension : Portosystemic shunts: rectal varices, splenorenal shunts, repermeabilization of the umbilical vein.
and/or splenic elasticity \> 50 kPa.
Patients naive to treatment with cardioselective beta blockers
Affiliated to french health insurance system

Exclusion Criteria30

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.

Interventions

DRUGCarvedilol

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.