NCT06687265Toboroz2. fázis
Effects of Metformin on Hepatic Venous Pressure Gradient in Patients With Cirrhosis and Portal Hypertension
Effects of Metformin on Hepatic Venous Pressure Gradient in Patients With Cirrhosis and Portal Hypertension - A Randomized Placebo-controlled Study
Forrás: ClinicalTrials.gov · Utoljára frissítve: 2025. ápr. 13. · Több mint 12 hónapja nem frissült - kérdezd meg a helyszínt, nyitott-e még
Rövid összefoglaló (regiszter, angolul)
Portal hypertension (PHT) is defined by an elevated pressure gradient between the portal vein and the hepatic veins ≥ 5 mm Hg, and is the main vector of complications in cirrhosis. When the hepatic venous pressure gradient (HVPG) is ≥ 10 mm Hg, it is considered as a " clinically significant PHT ": ascites and oesophageal varices (EV) may occur. Above 12 mm Hg, there is a risk of variceal bleeding. Carvedilol, a non-selective beta-blocker (NSBB), is recommended in all the patients with cirrhosis and clinically significant PHT in order to prevent decompensation of cirrhosis. Nevertheless, 40 % of patients are NSBB non-responders, i.e. they do not show a significant decrease in HVPG. In addition, NSBB responders treated for primary prophylaxis have an incidence of variceal bleeding of approximately 10% per year, with a six-week mortality of 20%. Therefore, there is an unmet need for PHT in patients with cirrhosis who do not respond to NSBB, and also for an increase in efficacy in responders. In a randomised pilot study, Rittig et al. observed a mean change in HVPG of -2,9 mm Hg in 16 patients with cirrhosis and HVPG ≥ 12 mm Hg, not treated with NSBB, 90 minutes after ingestion of 1000 mg metformin. The study will be a prospective, national, multicentre, phase II, superiority comparative randomized (1:1) simple-blinded clinical trial with two parallel arms: metformin versus placebo. The main objective is 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. Subjects randomized in the metformin group or placebo group will receive metformin ou placebo, one pill of 500 mg per os twice a day (one in the morning and one in the evening, during or at the end of the meal) for 28 days.
- Állapot (regiszter)
- Toboroz
- Fázis (regiszter)
- 2. fázis
- Vizsgálattípus
- Beavatkozással járó
- Résztvevők száma
- 76 (tervezett)
- Első benyújtás
- 2024. okt. 31.
- Kezdés
- 2025. márc. 10.
- Elsődleges befejezés
- 2027. márc. 30.
- Fő szponzor
- Assistance Publique - Hôpitaux de Paris
- NCT-szám
- NCT06687265
Mit vállalsz
- Vizsgálat típusa: Beavatkozással járó · 2. fázis
- Tervezett résztvevők: 76
- 2025. márc. 10. és az elsődleges befejezés (2027. márc. 30.) között
- 1 helyszín, 1 országban
- Vizitek és vizsgálatok: kérdezd a vizsgálat csapatát, a regiszter nem sorolja fel őket
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Korábbi kezelés
- Ongoing treatment with metformin, or discontinued for less than 3 months
- Treatment with statins started or discontinued for less than 3 months
- Treatment with nucleoside/nucleotide analogue for HBV, or direct-acting antiviral treatment for HCV, started for less than 6 months
Más betegség
- Known hypersensitivity to the active substance or any of the excipients
- History of lactic acidosis, diabetic acidocetosis, or diabetic precoma
- Ongoing condition that may lead to acute kidney injury or hypoxia: dehydration, severe infection, shock, cardiac decompensation, respiratory failure, or myocardial infarction within the past month
- Known hypersensitivity to all the iodin-containing contrast agents
- Known hypersensitivity to lidocaine for local anesthesia
- Known hypersensitivity to beta-lactam antibiotics if the patient has a history of valve replacement
- Extra-hepatic cancer without remission
- Severe chronic kidney disease defined as estimated glomerular filtration rate < 30 mL/min/1,73m2 using the MDRD-6 formula
- Complete portal vein thrombosis (main portal trunk, or right branch), or portal cavernoma
- History of TIPS (transjugular intrahepatic portosystemic shunt) / surgical portosystemic derivation / liver transplantation / major hepatectomy
Laborértékek
- Serum total bilirubin > 50 µmol/L
- Transaminases > 5 ULN
Egyéb
- Prothrombin ratio < 50 %
- Need for at least one paracentesis for ascites fluid evacuation in the last 6 months
- Expected follow-up < 3 months
- Alcohol consumption > 14 units/week for women or > 21 units/week for men, current or abstinent for less than 6 months
- Biliary cirrhosis
- Hepatocellular carcinoma with at least one nodule > 3 cm in diameter, or more than 3 nodules
- Cholangiocarcinoma
- Ongoing participation in another interventional therapeutic trial
- Pregnant or breastfeeding women
- Patients unable to give consent (under guardianship or curatorship)
- Non-randomisation criteria: HVPG < 12 mm Hg at the catheterism performed during the first follow-up visit
Kiket keres a vizsgálat
- - 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, or on the following criteria:
- Investigator's judgement
- active cause of cirrhosis and:
- History of clinical ascites
- Or history of variceal bleeding
- Or liver stiffness by VCTE ≥ 35 kPa on carvedilol in the last two years
- or spleen stiffness by VCTE ≥ 55 kPa on carvedilol in the last two years
- or liver surface nodularity ≥ 2,9 in the last two years
- or HVPG \> 16 mm Hg prior to starting NSBB
- or Laennec 4c cirrhosis on histology
- or resolution of the cause of cirrhosis for at least 6 months and:
- history of clinical ascites in the last 6 months
- or history of variceal bleeding in the last 6 months
- or liver stiffness by VCTE ≥ 35 kPa on carvedilol in the last 6 months
- or spleen stiffness by VCTE ≥ 55 kPa on carvedilol in the last 6 months
- or liver surface nodularity ≥ 2,9 in the last 12 months
- or Laennec 4c cirrhosis on histology in the last 12 months
- 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
Életkor a regiszterben: 18 év – - · Nem: nők és férfiak · Egészséges önkénteseket nem fogad
Helyszínek (1)
Helyszínek a regiszter sorrendjében. Ha a profilodba mented a városodat, távolság szerint rendeződnek.
| Helyszín | Város | Ország | Helyszín állapota |
|---|---|---|---|
| Facility Name: Beaujon hospital | Clichy | Franciaország | Toboroz |
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