A Pilot Study to Examine the Role of Nitazoxanide to Prevent Recurrence of Hepatitis C After Transplantation
Condition: Hepatitis C Recurrence
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Recurrence
Study type: Interventional
Phase: Phase 1

Summary: 
      Recurrence of Hepatitis C virus infection (HCV) is universal after orthotopic liver
      transplantation (LTx) and is associated with allograft failure, death and need for
      re-transplantation. Currently, there are no effective therapies to prevent HCV recurrence.
      Nitazoxanide (NTZ), an oral thiazolide anti-infectious agent, was safe, well tolerated and
      effective in achieving sustained viral response in patients with chronic HCV genotype 4. Its
      role in the prevention of HCV recurrence after liver transplantation has not been studied.
      The investigators propose to conduct an open label pilot study examining the role of NTZ in
      the prevention of HCV re-infection in eight patients undergoing LTx. First time transplant
      recipients for chronic HCV without history of renal failure or HIV/HBV co-infection, will
      receive NTZ immediately prior to LTx and for 3 days thereafter. The primary endpoint is the
      number of patients who remain HCV-RNA-negative at day 7 after LTx. If at least one patient
      remains negative, the study will be determined to be positive. Additionally, the
      investigators will examine the viral kinetics of HCV, tolerability and safety of NTZ.
    

Detailed description: 
      Recurrence of Hepatitis C virus infection (HCV) is universal after orthotopic liver
      transplantation (LTx) and is associated with allograft failure, death and need for
      re-transplantation. Currently, there are no effective therapies to prevent HCV recurrence.
      Nitazoxanide (NTZ), an oral thiazolide anti-infectious agent, was safe, well tolerated and
      effective in achieving sustained viral response in patients with chronic HCV genotype 4. Its
      role in the prevention of HCV recurrence after liver transplantation has not been studied. We
      propose to conduct an open label pilot study examining the role of NTZ in the prevention of
      HCV re-infection in eight patients undergoing LTx. First time transplant recipients for
      chronic HCV without history of renal failure or HIV/HBV co-infection, will receive NTZ
      immediately prior to LTx and for 3 days thereafter. The primary endpoint is the number of
      patients who remain HCV-RNA-negative at day 7 after LTx. If at least one patient remains
      negative, the study will be determined to be positive. Additionally, we will examine the
      viral kinetics of HCV, tolerability and safety of NTZ.
    

Intervention name(s): Nitazoxanide
Intervention type(s): Drug
Intervention description(s): Drug administration: The drug will be available through the research pharmacy. Patients will receive 1000mg (2 tablets) oral NTZ or an equivalent dose of NTZ suspension 1500mg (75mL) according to the schedule below.
Dose timing Dose Schedule Interval Dose Pre-transplant(on admission) 1000mg oral Once Total 1 dose Pre-transplant (delayed surgery >12 hours) 1000mg oral Every 12 hrs Variable Post operative dose 1000mg oral/ nasogastric tube Every 12 hrs Total 6 doses
All attempts will be made to administer the tablet form of the medication, given the higher area under the curve that is achieved. If needed, the suspension formulation will be used. Since the suspension form has 70% bioavailability, the suspension dose administered will be 1.5 grams every 12 hours until the tablet form can be given.
Intervention MeSH terms: Nitazoxanide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: nitazoxanide; liver transplantation; HCV recurrence