A Pilot Study to Examine the Role of Nitazoxanide to Prevent Recurrence of Hepatitis C After Transplantation - Full Text View

Purpose

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.

Condition	Intervention	Phase
Hepatitis C Recurrence	Drug: Nitazoxanide	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Prevention
Official 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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C Liver Transplantation

Drug Information available for: Nitazoxanide

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:

undetectable HCV RNA by real-time reverse transcription PCR on day 7 after transplantation. [ Time Frame: at day 7 ] [ Designated as safety issue: No ]
undetectable HCV RNA by real-time reverse transcription PCR on day 7 after transplantation.

Secondary Outcome Measures:

Viral Kinetics [ Time Frame: 4 months ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
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.

Enrollment:	8
Study Start Date:	February 2009
Study Completion Date:	January 2011
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Nitazoxanide arm All patients will receive nitazoxanide	Drug: 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.

Arms

Assigned Interventions

Experimental: Nitazoxanide arm

All patients will receive nitazoxanide

Drug: 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.

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01074203

Locations

United States, Minnesota
Mayo Clinic College of Medicine
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

Investigators

Principal Investigator:

W Ray Kim, MD

Mayo Clinic College of Medicine

More Information

No publications provided

Responsible Party:	W Ray Kim, Mayo Clinic College of Medicine
ClinicalTrials.gov Identifier:	NCT01074203 History of Changes
Other Study ID Numbers:	08-006000
Study First Received:	February 22, 2010
Last Updated:	July 27, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Mayo Clinic:

nitazoxanide
liver transplantation
HCV recurrence

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis C
Recurrence
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections

RNA Virus Infections
Flaviviridae Infections
Disease Attributes
Pathologic Processes
Nitazoxanide
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013