Carvedilol effect on portal pressure measured by endoscopic ultrasound

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

We will test whether one month of carvedilol (titrated to 12.5 mg daily) lowers portal pressure to help prevent digestive bleeding in adults with cirrhosis.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Clermont-Ferrand (other)
• Locations: 2 sites (Clermont-Ferrand and 1 other locations)
• Trial ID: NCT06861075 on ClinicalTrials.gov

What this trial studies

This open-label interventional study gives adults with cirrhosis carvedilol, starting at a low dose and titrated to 12.5 mg/day, and measures the portal pressure gradient by endoscopic ultrasound (EUS-PPG) at baseline and after about one month of treatment. Participants undergo an initial oesogastroduodenal endoscopy with EUS-PPG, scheduled clinic visits for safety monitoring and dose titration, and a follow-up endoscopy with repeat EUS-PPG at 30–45 days. Eligibility is based on suspected portal hypertension by Baveno VII criteria, radiologic signs, or high splenic stiffness, and patients must be naive to cardioselective beta blockers. The trial is conducted at CHU Clermont-Ferrand with routine clinical monitoring (vitals, ECG if indicated, adverse event reporting) throughout the 90-day protocol period.

Who should consider this trial

Good fit: Adults (≥18) with cirrhosis and suspected portal hypertension by Baveno VII criteria, radiologic signs, or elevated splenic stiffness who have not previously used cardioselective beta blockers and are affiliated with the French health insurance system.

Not a fit: Patients with absolute contraindications to beta blockers, prior beta-blocker treatment, or without evidence of portal hypertension are unlikely to receive benefit from this intervention.

Why it matters

Potential benefit: If successful, this could lower portal pressure and reduce the risk of digestive bleeding in people with cirrhosis.

How similar studies have performed: Non-selective beta blockers including carvedilol have previously been shown to lower portal pressure and reduce bleeding risk, while EUS-guided portal pressure measurement is a relatively new method for directly measuring hemodynamic response.

Eligibility criteria

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.

Where this trial is running

Clermont-Ferrand and 1 other locations

• Lise Laclautre — Clermont-Ferrand, France (NOT_YET_RECRUITING)
• Chu Estaing Medecine Digestive Et Hepatobiliaire — Clermont-Ferrand, France (RECRUITING)

Study contacts

• Principal investigator: Armando Abergel — University Hospital, Clermont-Ferrand
• Study coordinator: Lise Laclautre

Conditions: Cirrhosis, Portal Hypertension Related to Cirrhosis, Carvedilol., Portal hypertension in cirrhosis., EUS-PPG measurement.