Completed

NCT Number: NCT01074203

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

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.

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Key information

Conditions

Hepatitis C Recurrence

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Mayo Clinic College of Medicine

Rochester, Minnesota, 55905, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Nitazoxanide

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.

Primary outcomes

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

Time frame: at day 7

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

Secondary outcomes

Viral Kinetics

Time frame: 4 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.
Safety

Time frame: 7 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.

Sponsors and collaborators

Lead sponsor

Mayo Clinic

Other

Registry information

Official study title

A Pilot Study to Explore a Potential Role of Nitazoxanide (NTZ) in the Prevention of Recurrent Hepatitis C Virus (HCV) Infection After Orthotopic Liver Transplantation

Important dates

Study start: 2009
Primary completion: 2011
Study completion: 2011
First posted: Feb 24, 2010
Registry last updated: Jul 31, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.