Efficacy of the combination of simvastatin plus rifaximin in patients with decompensated cirrhosis to prevent ACLF development: a multicenter, double-blind, placebo controlled randomized clinical trial.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 28

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. (only if refraining from heterosexual
intercourse during the period of twelve months of duration of the study and
extended to 30 days after the end of the study treatment) Hormonal
contraceptive methods will be avoided due to the risk of adverse events and
impairment of liver function.

Exclusion Criteria

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. Patients under anticoagulant therapy will be excluded if the INR
values are >= 3.5
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.
27. Creatinine clearance < 30 ml/min
28. Patients with cirrhosis due to cholestatic liver disease can only be
included in the study if they present clinical decompensation of cirrhosis
(i.e. ascites).
29. Patients with previous organ transplantation.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Efficacy of treatment in halting the progression of decompensated cirrhosis as<br /><br>assessed by time to first ACLF during the treatment period, defined according<br /><br>to criteria by Moreau et al., Gastroenterology 2013.</p><br>

Secondary Outcome Measures

Name	Time	Method

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