Portal hypertension in cirrhosis

Start 4 Mar 2025 · Status Ongoing, recruiting · 1 EU/EEA countries · 10 sites · Protocol APHP230872

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Ongoing, recruiting

Participants planned 76

Countries 1

Sites 10

Portal hypertension (PHT) and consequences in complications of cirrhosis

To evaluate the effect of metformin versus placebo during 28 days on HVPG, in patients with cirrhosis and a HVPG ≥ 12 mm Hg already treated with carvedilol. Objectif of the ancillary study : To study the effect of metformin on postprandial changes in systemic haemodynamics and HVPG.

Key facts

Sponsor: Assistance Publique Hopitaux De Paris
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
Trial duration: 4 Mar 2025 → ongoing
Decision date (initial): 2024-09-04
Transition trial: No
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: PHRC IR Ile de France 2022/AOR22044

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the effect of metformin versus placebo during 28 days on HVPG, in patients with cirrhosis and a HVPG ≥ 12 mm Hg already treated with carvedilol.
Objectif of the ancillary study : To study the effect of metformin on postprandial changes in systemic haemodynamics and HVPG.

Secondary objectives 8

- To evaluate the safety and tolerability of metformin in patients with cirrhosis and a HVPG ≥ 12 mm Hg
- To evaluate the rate of change in HVPG after 28 days of treatment
- To evaluate the rate of patients with a clinically significant improvement in HVPG
- To assess the change in systemic haemodynamics after 28 days of treatment
- To assess the change in liver steatosis after 28 days of treatment
- To assess the performance of liver and spleen stiffness by vibration-controlled transient elastography (VCTE) using FibroScan® (Echosens, Paris, France) to estimate the haemodynamic response to the treatment
- To assess the performance of liver and spleen stiffness by 2D-shear wave elastography using Aixplorer® (SuperSonic Imagine, Aix-en-Provence, France) to estimate the haemodynamic response to the treatment
- To assess the effect of metformin on systemic inflammation, coagulation, hepatocyte stress, and endothelial function.

Conditions and MedDRA coding

Portal hypertension (PHT) and consequences in complications of cirrhosis

Version	Level	Code	Term	System organ class
20.0	LLT	10020786	Hypertension portal	10019805

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

- Age ≥ 18 years
- Written informed consent to participate in the study
- Medical insurance coverage
- For child-bearing aged women, contraception using oestroprogestative, progestative, intrauterine device, or mechanical contraception
- Diagnosis of cirrhosis based on a liver biopsy, or on clinical, biological, endoscopic, and radiological evidence
- Active cause of cirrhosis, or resolution (alcohol cessation, sustained virological response to direct-acting antiviral treatment for HCV, initiation of nucleoside/nucleotide analog treatment for HBV) for at least 6 months
- Child-Pugh A or B
- High likelihood of HVPG ≥ 12 mm Hg based on investigator’s judgement, _confer criteria in the protocole
- Treatment with carvedilol (≥ 6,25 mg/day) at a stable dose for at least one month
- Absence of hepatocellular carcinoma outside at least one nodule > 3 cm in diameter, or more than 3 nodules, on ultrasound, CT-scan or MRI performed during the previous 6 months

Exclusion criteria 4

- Serum total bilirubin > 50 µmol/L
- Prothrombin ratio < 50 %
- Transaminases > 5 ULN
- Need for at least one paracentesis for ascites fluid evacuation in the last 6 months

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

the hepatic venous pressure gradient (HVPG) after 28 days of treatment
Endpoints of the ancillary study: Changes in systemic haemodynamics and HVPG 30 minutes after a meal consisting of two 200 mL bottles of hypercaloric/hyperprotic Fortimel Energy

Investigational products

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

Test 1

Metformin Embonate

SCP10310250 · ATC

Active substance: Metformin Embonate
Substance synonyms: Metformin hemiembonate, METFORMIN PAMOATE
Route of administration: ORAL USE
Max daily dose: 1 g gram(s)
Max total dose: 28 g gram(s)
Max treatment duration: 4 Week(s)
Authorisation status: Authorised
ATC code: A10BA02 — METFORMIN
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Placebo 1

Placebo 515

N/A · Product

Other product name: N/A
Pharmaceutical form: N/A
ATC code: N/A — N/A
Marketing authorisation: N/A
MA holder: N/A
MA country: Iceland
Paediatric formulation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation: Assistance Publique Hopitaux De Paris
Address: Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
City: Paris Cedex 10
Postcode: 75475
Country: France

Scientific contact point

Organisation: Assistance Publique Hopitaux De Paris
Contact name: Lucile Moga

Public contact point

Organisation: Assistance Publique Hopitaux De Paris
Contact name: Lucile Moga

Locations

1 EU/EEA country · 10 investigational sites

By country

Country	MS status	Planned subjects	Sites
France	Ongoing, recruiting	76	10
Rest of world	—	0	—