Cirrose decompensated liver cirrhosis liver damage with loss of function
Conditions
Interventions
Simvastatin 20mg or 40mg tablets and placebo of simvastatin + Rifaximin 400mg
tablets and placebo of rifaximin
Decompensated cirrhosis
LIVERHOPE
Rifaximin
Sponsors
IDIBAPS (Institut d' Investigacions Biomediques August Pi i Sunyer)
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years old. 2. Cirrhosis defined by standard clinical criteria and ultrasonographic findings and/or histology. Cirrhosis of any etiology may be included. Patients with cirrhosis of autoimmune etiology on treatment with corticosteroids must be on stable corticosteroid dose for >=3-month period before study inclusion. 3. Child Pugh B/C patients (from 7 to 12 points). 4. Women of child-bearing potential must have a negative pregnancy test in urine before the inclusion of the study and agree to use highly effective contraceptive methods (combined oral pill, injectable or implanted contraceptive, intrauterine device / intrauterine hormone-releasing system) during the study.
Exclusion criteria
Exclusion criteria: 1. Patients on treatment with statins or rifaximin one month before study inclusion. 2. Patients on the waiting list for liver transplantation. 3. Patients with acute-on-chronic liver failure according to the criteria published by Moreau et al. (see appendix 1) 4. Serum creatinine >=2 mg/dL. 5. Serum bilirubin>5 mg/dL. 6. INR >=2.5. 7. Patients with CK elevation of 50% or more above the upper limit of normal at study inclusion. 8. Bacterial infection within 15 days before study inclusion. 9. Gastrointestinal bleeding within 15 days before study inclusion. 10. Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy. 11. HIV infection. 12. Hepatocellular carcinoma outside Milan criteria, defined as a single nodule = 32 and/or ABIC score > 6.7). 25. Refusal to give informed consent. 26. Patients with contraindications for statins or rifaximin. 27. Known hypersensitivity to rifaxamin (or rifamycin derivatives) or to simvastatin.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in transaminases, alkaline phosphatase and creatine kinase during the treatment period, to evaluate treatment-related toxicity. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Appearance of muscle toxicity at weeks 2, 4, 6, 8, 10 and 12 as defined using a specific statin-associated myopathy questionnaire (see appendix 2). - Changes from baseline in plasma renin concentration, serum aldosterone, plasma norepinephrine, and plasma copeptin levels at weeks 2, 4, 8 and 12. - Changes from baseline in a large array of plasma cytokine levels including, but not limited to, VCAM-1, VEGF-A, Fractalkine, MIP-1a, Eotaxin, IP-10, RANTES, GM-CSF, IL-1β, IL-2, ICAM-1, MCP-1, L-6, and IL-8, as well as an oxidized form of albumin, human nonmercaptalbumin-2 (HNA2) at weeks 2, 4, 8 and 12. - Changes from baseline in plasma biomarkers FABP4 and CD-163 and urine biomarkers NGAL, IL-18, MCP-1, osteopontin, and albumin at weeks 2, 4, 8 and 12. - Changes in blood levels of bacterial DNA or bacterial products at weeks 2, 4, 8 and 12. - Assessment of genetic polymorphisms of statins membrane transporter OATPB1 in patients developing treatment-related toxicity (defined as the primary endpoint of the study). - Proportion of patients with treatment-related serious adverse events during the study period. | — |
Countries
France, Germany, Italy, Netherlands, Spain, United Kingdom
Outcome results
None listed