Body-weight Reduction Effect on Portal Hypertension in Compensated Cirrhosis

What this study is testing ClinicalTrials.gov NCT07797101 ↗

Description as written by the study sponsor.

Obesity and metabolic abnormalities accelerate decompensation in compensated cirrhosis, driven by clinically significant portal hypertension (CSPH, HVPG≥10 mmHg). Lifestyle-induced weight loss can lower portal pressure, but pharmacological options are limited. Mazdutide, a dual GLP-1/glucagon receptor agonist, has proven weight-loss and glycaemic benefits, yet its safety and efficacy in cirrhosis with portal hypertension are unknown. This investigator-initiated, single-arm, open-label, exploratory trial evaluates whether mazdutide can safely reduce portal pressure in overweight patients with compensated cirrhosis and CSPH. The main questions it aims to answer are: Does 16-week mazdutide treatment reduce HVPG (percentage change from baseline)? What adverse events occur, and is the drug tolerated? Participants will: Receive mazdutide SC injection once weekly for 16 weeks, titrated from 2 mg to 4 mg to 6 mg (if tolerated), with dose adjustment for intolerance. Undergo HVPG at baseline and week 16 (primary endpoint). Have FibroScan® (liver/spleen stiffness, CAP) at baseline and weeks 4, 8, 12, 16. Provide blood samples for liver, renal, glucose, lipid, and coagulation tests at each visit. Undergo body composition, handgrip strength, and nutritional assessments to monitor muscle mass. Attend clinic visits every 4 weeks during treatment and one follow-up visit 4 weeks post-treatment. Key eligibility: Adults 18-75 with compensated cirrhosis (viral, MASLD, or alcohol-related), HVPG≥10 mmHg, BMI≥28 or ≥26 with comorbidities, stable weight, and stable carvedilol/propranolol if used. Exclude prior decompensation, HCC, CTP≥B8, eGFR\<60, mazdutide contraindications, active infection, uncontrolled hepatitis, portal vein thrombosis, etc. Endpoints: Primary - % change in HVPG. Secondary - HVPG response (≥10% decrease or \<10 mmHg), decompensation events, treatment discontinuation due to AEs. Exploratory - changes in stiffness, liver fat, metabolic parameters, body composition, nutrition. Safety: AEs (CTCAE v5.0), labs, vitals, with special monitoring for GI symptoms, dehydration, renal function, hepatic encephalopathy, muscle loss, pancreatitis, and gallbladder events. Sample size and analysis: 50 patients. Primary endpoint analysed by paired t-test or Wilcoxon (α=0.05, two-sided) in FAS and PPS. Secondary endpoints mainly descriptive; key secondary tested for support. Subgroup analyses planned if feasible. Study duration: 20 weeks (2-week screening, 16-week treatment, 4-week follow-up). Conducted at Second Affiliated Hospital of Chongqing Medical University, China. Ethics approved, informed consent required. This study will provide first evidence on mazdutide for portal hypertension in overweight cirrhosis.

Treatments tested

• Mazdutide injection Drug

  Mazdutide injection is a sterile, clear to almost colorless liquid formulated for subcutaneous administration. It is supplied in three fixed-dose strengths for this study: 2 mg/0.5 mL, 4 mg/0.5 mL, and 6 mg/0.5 mL. Participants assigned to this arm receive once-weekly subcutaneous injections over a 16-week active treatment period. The regimen begins with a forced dose-titration phase: 2 mg weekly for the first 4 weeks, followed by 4 mg weekly for the next 4 weeks, and then 6 mg weekly for the final 8 weeks, provided the preceding dose is tolerated. In cases of treatment-emergent adverse events (CTCAE grade ≥2 or intolerable grade 1), the investigator may temporarily withhold the dose, step down to the next lower dose level (6 mg→4 mg→2 mg), or permanently discontinue the drug. After symptom resolution, gradual re-escalation (2 mg→4 mg→6 mg) may be attempted at the investigator's discretion.