LIVE-C-Free: Early and Late Treatment of Hepatitis C With Sofosbuvir/Ledipasvir in Liver Transplant Recipients
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: Sofosbuvir/Ledipasvir x 12 weeks; Sofosbuvir/Ledipasvir + Ribavirin x 12 weeks
Intervention MeSH terms: Ribavirin; Sofosbuvir; Ledipasvir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The predominant remaining questions for post-transplant treatment of Hepatitis C virus (HCV)
      in the DAA (direct acting anti-virals) era are whether a ribavirin-free regimen is possible
      and whether pre-emptive treatment is now a potential option to prevent long-term damage to
      the allograft.

      Our aim is to provide answers to these primary questions with our multicenter, prospective,
      randomized, open-label intent-to-treat phase IV study
    

Eligibility criteria:

        Inclusion Criteria

          1. At least 18 years of age and able to give informed consent

          2. History of HCV genotype 1 or 4

          3. Normal EKG

          4. At least 91 days post orthotopic liver transplant

          5. Screening laboratory values within defined thresholds

          6. Detectable HCV RNA at screening

          7. Creatinine Clearance of at least 40ml/min using the Cockcroft Gault equation

          8. Negative pregnancy test for female subjects within 48 hours prior to receiving study
             medication

          9. Use of two effective contraception methods if female of childbearing potential or
             sexually active male unless status post bilateral tubal ligation, bilateral
             oophorectomy, hysterectomy, or vasectomy

        Exclusion Criteria

          1. Serious or active medical or psychiatric illness

          2. History of significant or unstable cardiac disease

          3. Stomach disorder that could interfere with the absorption of the study drug

          4. Pregnant or nursing females or males with a pregnant female partner

          5. Co-infected with Hepatits B (HBV) or HIV

          6. Recipients of an allograft from a donor that was infected with HCV with an unknown
             genotype or non-genotype 1 or 4 unless the recipient is demonstrated to have only
             genotype 1 or 4 HCV replication post-transplant

          7. Allergic to or intolerant of sofosbuvir, ledipasvir, or ribavirin

          8. History of exposure to an Nonstructural protein (NS5A) inhibitor

          9. Within 1 year of transplant AND history of Hepatocellular Carcinoma (HCC) with tumor
             burden outside of the Milan Criteria (See Appendix II) prior to transplant

         10. Participated in a clinical study with an investigational drug or biologic within the
             last 30 days

         11. Combined liver/kidney transplant

         12. History of organ transplant other than liver

         13. Childs Turcotte Pugh (CTP) B or C

         14. Patients with fibrosing cholestatic hepatitis

         15. Platelet count of ≤ 30 k/mm3

         16. Hemoglobin < 10g/dL

         17. Total bilirubin > 10mg/dL

         18. Alanine aminotransferase (ALT),aspartate aminotransferase (AST), or alkaline
             phosphatase ≥ 10x upper limit normal

         19. Serum sodium < 125mmol/L

         20. Current use of any of the Prohibited Interventions (Section 5.3.2) and un-willing to
             discontinue use, or use of amiodarone within 6 months of screening