Effect of Carvedilol on the portosystemic gradient as measured by endoscopic ultrasound

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Hospital Of Clermont-Ferrand

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

16 Apr 2025 → ongoing

Decision date (initial)

2025-01-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518302-41-00

ClinicalTrials.gov

NCT06861075

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the efficacy at one month of Carvedilol 12.5 mg per day, in primary prophylaxis of digestive hemorrhage linked to PH of cirrhotic origin, by measuring the portosystemic gradient by echo-endoscopy.

Secondary objectives 3

1. To assess the three-month tolerance of Carvedilol 12.5 mg per day, as primary prophylaxis of digestive hemorrhage linked to PH of cirrhotic origin.
2. To evaluate the three-month efficacy of carvedilol in preventing rupture of gastroesophageal varices.
3. To evaluate the variation of the different biological and elastometric parameters measured after taking Carvedilol for three months.

Conditions and MedDRA coding

cirrhotic portal hypertension

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Patient ≥ 18 years with suspected cirrhotic PH (all causes combined) 1 : according to Baveno VII criteria: Liver elasticity ≥ 25 kPa or Liver elasticity between 20 and 25 kPa with Platelets < 150 G/L or Liver elasticity between 15 and 20 kPa with Platelets < 110 G/L or Liver elasticity > 20 kPa and/or Platelets < 150 G/L for patients with cirrhosis developed from NASH or Gastroesophageal varices at high risk of rupture: Size > 5 mm (stage 2 or 3) or Size ≤ 5 mm and red signs or Size ≤ 5 mm and CHILD-PUGH C. 2. and/or the presence of a radiological sign of PHT: Porto-systemic shunts: rectal varices, splenorenal shunts, re-canalization of the umbilical vein. 3. and/or splenic elasticity > 50 kPa.
2. Patient naïve to any treatment with non-cardioselective beta-blockers.
3. Affiliation to a Social Security scheme.

Exclusion criteria 13

1. Absolute contraindications to beta-blockers: bradycardia ≤ 50 bpm, systolic arterial hypotension (systolic arterial pressure ≤ 90 mmHg), grade II or III atrioventricular block, decompensated heart failure, pulmonary arterial hypertension, severe peripheral arterial disease, Raynaud's syndrome, asthma.
2. Presence of severe acute alcoholic hepatitis (Madrey score ≥ 32).
3. Current hepatic encephalopathy ≥ Grade 2.
4. Hepatorenal syndrome in progress.
5. Clinical ascites of great abundance: only if bothersome for the feasibility of the EHH.
6. History of ruptured esophageal varices.
7. Hepatocellular carcinoma active or in remission for less than six months.
8. Active or resolved portal vein thrombosis for less than six months.
9. Digestive surgical history not allowing the feasibility of measuring the portosystemic gradient by echo-endoscopy (gastrectomy, bypass, etc.).
10. Patients on antiplatelet drugs (except acetylsalicylic acid) or on anticoagulants for emboligenic AC/AF.
11. Severe chronic renal failure stage 4 or end-stage renal failure stage 5 (clearance < 30 mL/min).
12. Pregnant or breastfeeding women, or those planning to become pregnant. A pregnancy test will be performed for women of childbearing age.
13. Patients protected by law (under guardianship, curatorship or legal protection) or deprived of their liberties.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Hemodynamic response (binary efficacy criterion) at one month, defined by a decrease of at least 10% in the echo-endoscopic portosystemic gradient compared to the baseline value measured at inclusion.

Secondary endpoints 3

1. Top ten side effects of beta-blockers reported in the literature, and percentage of patients who discontinue treatment due to side effects.
2. Digestive bleeding linked to rupture of esophageal or gastric varices within three months of starting treatment.
3. Biological and elastometric parameters measured before and after taking Carvedilol for three months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Hospital Of Clermont-Ferrand

Sponsor organisation

University Hospital Of Clermont-Ferrand

Address

58 Rue Montalembert

City

Clermont Ferrand Cedex 1

Postcode

63003

Country

France

Scientific contact point

Organisation

University Hospital Of Clermont-Ferrand

Contact name

Lise Laclautre

Public contact point

Organisation

University Hospital Of Clermont-Ferrand

Contact name

Lise Laclautre

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications