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A Pilot Study to Examine the Role of Nitazoxanide to Prevent Recurrence of Hepatitis C After Transplantation

Phase 1
Completed
Conditions
Hepatitis C Recurrence
Interventions
Registration Number
NCT01074203
Lead Sponsor
Mayo Clinic
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
8
Inclusion Criteria
  • Adult male or female patients age 18-75
  • HCV infection identified by positive, quantifiable HCV RNA prior to transplant
Exclusion Criteria
  • Scheduled recipient of living donor transplantation
  • History of chronic hepatitis B or HIV infection
  • Transplantation for fulminant hepatic failure
  • Estimated glomerular filtration rate <60ml/min
  • Women who are pregnant or breast feeding and men or women that are sexually active but do not agree to use acceptable birth control

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Nitazoxanide armNitazoxanideAll patients will receive nitazoxanide
Primary Outcome Measures
NameTimeMethod
undetectable HCV RNA by real-time reverse transcription PCR on day 7 after transplantation.at day 7

undetectable HCV RNA by real-time reverse transcription PCR on day 7 after transplantation.

Secondary Outcome Measures
NameTimeMethod
Viral Kinetics4 months

Viral Kinetics: The decline in HCV RNA will be calculated using the HCV RNA levels obtained during the study at the 12 time points.

Safety7 days

Safety of NTZ: The safety and tolerability of NTZ will be monitored by evaluating vital signs, change in laboratory data from baseline, adverse events, UPIRSTOs, dose adjustments and incidence of early drug withdrawal. Tolerability will be defined as the number of patients discontinuing medications or having a dose modification due to an adverse event.

Trial Locations

Locations (1)

Mayo Clinic College of Medicine

🇺🇸

Rochester, Minnesota, United States

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