Reversal of Hepatic Impairment in Patients With Hepatitis C Virus (HCV) and Early Decompensation of Cirrhosis
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: Simeprivir (SMV); Sofosbuvir (SOF); Ribavirin (RBV)
Intervention description: Experimental Single arm study. All participants will get the same treatment.; Experimental Single arm study. All participants will get the same treatment.; Experimental Single arm study. All participants will get the same treatment.
Intervention MeSH terms: Ribavirin; Sofosbuvir
Phase: Phase 3
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: HCV; Hepatitis C

Summary:

      1. Achieve sustained virologic response (SVR) in patients infected with HCV genotype 1,
           cirrhosis, and early clinical decompensation using 12 weeks of Olysio/Sovaldi/Ribavirin
           (or known as: Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin (RBV).

        2. Hepatic improvement during and after Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV)
           treatment using a new test of liver function, HepQuant-SHUNT.
    

Eligibility criteria:

        Inclusion Criteria:

          1. HCV genotype 1 infection (all subtypes and Q80K a type of mutation are allowed), and
             have been approved by a third party payer for the FDA-approved combination of
             sofosbuvir (SOF) plus ribavirin. The study drug, simeprevir (SMV)

          2. Biopsy proven cirrhosis, or clinical cirrhosis with APRI (AST to Platelet Ratio Index
             to determine clinical cirrhosis)> 2, Fibrotest > 0.75, or Fibroscan > 12.5 Results
             Stiffness (kPa).

          3. MELD 10 or less

          4. Expected survival without liver transplantation of >1 year

          5. Patients with Hepatocellular carcinoma (HCC) are included as long as disease MELD is
             10 or less, and anticipated time to transplant is >1 year. An example, might be a
             patient with a subcentimeter HCC who is undergoing serial imaging to document tumor
             growth to tumor diameter >2 cm prior to listing for transplantation (in order to
             secure MELD exception). In this case, there could be a time lapse of 3 months or more
             while monitoring tumor growth, and a further time lapse of 9 months or more until the
             time of transplantation.

          6. Patients with TIPS or Portal Vein Thrombosis may be included. -

        Exclusion Criteria:

          1. Inability to provide informed consent

          2. Known hypersensitivity or serious adverse reaction to any of the study drugs

          3. Age <18 or >80 years

          4. Pregnancy as determined by subject reporting and urine dipstick testing at screening.

          5. Other underlying chronic liver disease - examples that would exclude a patient from
             participating include but are not limited to nonalcoholic liver disease, alcoholic
             liver disease, hepatitis B, hemochromatosis, and autoimmune liver disease.

          6. Serious other underlying medical condition - examples include but are not limited to
             unstable cardiovascular, coronary, or pulmonary disease including right and left sided
             heart failure, active malignancy other than HCC, or serious infection.

          7. Estimated creatinine clearance < 30 mL min-1 1.73 m2 surface area (BSA)

          8. Hemoglobin <10 g/dL

          9. Neutrophils <500 /μL

         10. Platelets <50,000 /μL

         11. Bilirubin >4 mg/dL

         12. Albumin < 2.8 g/dL

         13. Blood Clotting: International Normalised Ratio (INR) > 2

         14. MELD >10

         15. Child-Turcotte-Pugh class B or C; or, CTP score >7

         16. Conditions that would affect the absorption of orally administered cholate used in the
             HepQuant® test - such as, extensive intestinal resection, diabetic gastroparesis, and
             ileal disease or resection.

         17. Concomitant use of both beta-blocker and ACE inhibitor

         18. Subjects taking any other medications with significant drug drug interactions related
             to the study medications (sofosbuvir, simeprevir, or ribavirin) who cannot discontinue
             or substitute that medication, will be excluded.