Simvastatin Plus Rifaximin in Decompensated Cirrhosis

• Status: Completed
• Trial end date: 2018-03-12
• Target enrollment: 0
• Participant gender: All

Summary

The main purpose of this study is to investigate whether the combination of two different drugs, simvastatin and rifaximin, is safe in the treatment of patients with decompensated cirrhosis.

The secondary purpose is to see if this combination results in an improvement in inflammation markers in patients with cirrhosis and in an improvement in analytic parameters of progression of liver disease.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Judit Pich
• Treatments: Rifamycins; Rifaximin; Simvastatin

Criteria

Inclusion Criteria:

• Age ≥ 18 years old.

• 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.

• Child Pugh B/C patients (from 7 to 12 points).

• 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:

• Patients on treatment with statins or rifaximin one month before study inclusion.

• Patients on the waiting list for liver transplantation.

• Patients with acute-on-chronic liver failure according to the criteria published by Moreau et al.

• Serum creatinine ≥2 mg/dL.

• Serum bilirubin>5 mg/dL.

• INR ≥2.5.

• Patients with CK elevation of 50% or more above the upper limit of normal at study inclusion.

• Bacterial infection within 15 days before study inclusion.

• Gastrointestinal bleeding within 15 days before study inclusion.

• Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy.

• HIV infection.

• Hepatocellular carcinoma outside Milan criteria, defined as a single nodule ≤5 cm or a maximum of 3 nodules with none >3 cm.

• Patients on antiviral therapy for HCV or those who have received it within the last 6 months.

• Patients with previous history of myopathy.

• Patients on treatment with potent inhibitors of CYP3A4 enzyme (See section 5.2:

Concomitant, nonpermitted and permitted medication)

• Patients on treatment with drugs with potential interactions with simvastatin

• Patients with a history of significant extrahepatic 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.

• Patients with current extrahepatic malignancies including solid tumours and hematologic disorders.

• Patients with previous history or increased risk of intestinal obstruction.

• Pregnancy or breastfeeding.

• Patients included in other clinical trials in the previous month.

• Patients with active alcohol consumption of more than 3 units per day.

• 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.

• Severe alcoholic hepatitis requiring corticosteroid therapy (Maddrey's Discriminant function ≥ 32 and/or ABIC score > 6.7).

• Refusal to give informed consent.

• Patients with contraindications for statins or rifaximin.

• Known hypersensitivity to rifaxamin (or rifamycin derivatives) or to simvastatin.