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

NCT ID: NCT01074203

Last Updated: 2012-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2011-01-31

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.

Conditions

Hepatitis C Recurrence

Keywords

nitazoxanide; liver transplantation; HCV recurrence

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Nitazoxanide arm

All patients will receive nitazoxanide

Group Type: EXPERIMENTAL

Nitazoxanide

Intervention Type: DRUG

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.

Interventions

Nitazoxanide

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 Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Mayo Clinic College of Medicine

Principal Investigators

W Ray Kim, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic College of Medicine

Locations

Mayo Clinic College of Medicine

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

08-006000

Identifier Type: -

Identifier Source: org_study_id