Efficacy of the combination of simvastatin plus rifaximin in patients with decompensated cirrhosis

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 240

Inclusion Criteria

Patients included into the study must meet all the following criteria:
1. Age = 18 years old.
2. Cirrhosis defined by standard clinical criteria, ultrasonographic findings and/or histology. Cirrhosis of any aetiology may be included. However, patients with cirrhosis due to autoimmune hepatitis must be on stable corticosteroid dose for =3-month period before study inclusion.
3. Child-Pugh B patients or Child-Pugh C patients (up to 12 points).
4. Women of child-bearing potential* must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence. Hormonal contraceptive methods will be avoided due to the risk of adverse events and impairment of liver function.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 240
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 240

Exclusion Criteria

Potential participants who meet any of the following criteria will be excluded from participation in this study:
1. Patients on treatment with statins or rifaximin up to one month before study inclusion.
2. Patients with contraindications for statins or rifaximin therapy.
3. Known hypersensitivity to simvastatin or rifaximin (or rifamycin derivatives).
4. Patients with CK elevation of 50% or more above the upper limit of normal at study inclusion.
5. Patients on treatment with potent inhibitors of CYP3A4 enzyme (see section 5.2: Concomitant, nonpermitted and permitted medication).
6. Patients on treatment with drugs with potential interactions with simvastatin (see section 5.2: Concomitant, nonpermitted and permitted medication).
7. Patients with previous history of myopathy.
8. Patients with previous history of intestinal obstruction or those who are at increased risk of this complication.
9. Patients with ACLF according to the criteria published by Moreau et al. (see appendix 2).
10. Serum creatinine =2 mg/dL (176.8 µmol/L).
11. Serum bilirubin>5 mg/dL (85.5 µmol/L).
12. INR =2.5.
13. Bacterial infection within 10 days before study inclusion.
14. Gastrointestinal bleeding within 10 days before study inclusion.
15. Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy according to the New-Haven classification.
16. Patients with active hepatocellular carcinoma or history of hepatocellular carcinoma that is in remission for less than six months for uninodular HCC or for less than 12 months for multinodular HCC within Milan criteria.
17. Patients on antiviral therapy for HCV or those who have received it within the last 6 months.
18. Severe alcoholic hepatitis requiring corticosteroid therapy (Maddrey’s Discriminant function = 32 and/or ABIC score > 6.7).
19. Patients with active alcohol consumption of more than 21 units per week.
20. HIV infection.
21. Patients with a history of significant extra hepatic disease with impaired short-term prognosis, including congestive heart failure New York Heart Association Grade III/IV, COPD GOLD >2, chronic kidney disease with serum creatinine >2mg/dL or under renal replacement therapy.
22. Patients with current extra hepatic malignancies including solid tumours and hematologic disorders.
23. Pregnancy or breastfeeding.
24. Patients included in other clinical trials in the month before inclusion.
25. Patients with mental incapacity, language barrier, bad social support or any other reason considered by the investigator precluding adequate understanding, cooperation or compliance in the study.
26. Refusal to give informed consent.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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