Study of the Impact of Nitazoxanide on Chronic Hepatitis Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mohamed Kohla, National Liver Institute, Egypt
ClinicalTrials.gov Identifier:
NCT01197157
First received: August 9, 2010
Last updated: September 27, 2014
Last verified: September 2014
  Purpose

The main objective of antiviral therapy of patients with chronic hepatitis C (CHC) is the sustained elimination of the hepatitis C virus (HCV). The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks according to HCV genotype.

However, this approach is not sufficient to substantially improve the sustained virologic response (SVR) rates. Therefore, new therapies are needed to treat patients with hepatitis C virus (HCV) infection. Nitazoxanide (NTZ), originally used to treat cryptosporidium parvum infection, recently was shown to have an unexpected antiviral activity in the HCV replicon system and in chronically infected patients.

The aim of this work is to study impact of nitazoxanide therapy in addition to peginterferon/ribavirin combination on virologic responses in patients with chronic hepatitis C genotype 4.

Patients will be enrolled in this study and will be randomly assigned in a 1:1 ratio into 2 groups:

Group A: comprises 100 CHC patients who will receive the standard of care treatment, peginterferon-alf 2a plus weight-based ribavirin for 48 weeks.

Group B: comprises 100 CHC patients who will receive nitazoxanide monotherapy at a dose of 500 mg twice daily for 12 weeks as a lead-in phase followed by triple therapy, nitazoxanide 500 mg twice daily plus peginterferon alfa-2a, and weight-based ribavirin for 48 weeks.

Data will be collected and statistical analysis will be done comparing the groups regarding response to antiviral therapy. Final results will be discussed and compared to similar studies published in peer reviewed journals and international conferences.


Condition Intervention Phase
Hepatitis C
Drug: Placebo
Drug: Nitazoxanide
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Impact of Nitazoxanide on Virologic Responses in Chronic HCV Infected Patients With Genotype 4: A Placebo-controlled Randomized Trial

Resource links provided by NLM:


Further study details as provided by National Liver Institute, Egypt:

Primary Outcome Measures:
  • Assessment of efficacy of Nitazoxanide as an add-on therapy in terms of achieving a sustained virologic response [ Time Frame: 180 ± 7 days after the end of triple therapy, the preliminary data will be available at least 2 years after the beginning of the study (September 2012) ] [ Designated as safety issue: No ]
    Patients in the 2 group who will continue on triple therapy till achieving an end-of-treatment response (after 48 weeks from the start of triple therapy), will have their viral load measured 6 months thereafter for assessment of sustained virologic response. patients in whom the virus is undetectble will be regarded as achieving a sustained virologic response.


Secondary Outcome Measures:
  • assessment of rapid virologic response [ Time Frame: 28-35 days from the start of triple therapy ] [ Designated as safety issue: No ]
    Patients in the 2 groups will have their viral load measured at 4 weeks from the start of triple therapy which is a strong predictor of attaining a sustained virologic response. patients in whom the virus is undetectable will be regarded as achieving a rapid virologic response.

  • Assessment of early virologic response [ Time Frame: 90 ± 7 days from the start of triple therapy ] [ Designated as safety issue: No ]
    Patients in the 2 groups will have their viral load measured at 12 weeks from the start of triple therapy. Patients in whom the virus is undetectable, will be regarded as achieving an early virologic response.

  • Assessment of end-of-treatment response [ Time Frame: 48± one week from the start of triple therapy ] [ Designated as safety issue: No ]
    Patients in the 2 groups will have their viral load measured at the end of triple therapy (48 weeks). Patients in whom the virus is undetectable, will be regarded as achieving an end-of-treatment response.

  • Safety of Nitazoxanide [ Time Frame: Throughout the study and up to 90 days after the end of triple therapy ] [ Designated as safety issue: Yes ]
    Safety of nitazoxanide will be assesses and all adverse events will be reported, and treatment will be discontinued if necessary

  • Assessment of the efficacy of Nitazoxanide monotherapy following the lead-in phase [ Time Frame: 90± 7 days from the start of the lead_in phase ] [ Designated as safety issue: No ]
    Patients in the 2 groups will have their viral load as well as transaminases (ALT&AST) measured at the end of the lead-in phase. in case of a reduction in viral load, this will be expressed as log10 reduction from nadir, also, reduction in serum transaminases from pre-treatment values will be regarded as achieving a biochemical response.


Enrollment: 200
Study Start Date: September 2010
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo

• Group A: comprises 100 chronic hepatitis patients who will receive placebo twice daily orally with food for an average of 12 weeks followed by the standard of care treatment, peginterferon Alfa 2a once weekly and weight-based ribavirin 1000 or 1200 mg/day (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses plus placebo twice daily for 48 weeks.

All patients in this group will have an HCV RNA within 3 months before initiation of therapy, in addition to ALT levels, CBC and other routine liver function tests.

Drug: Placebo
Group A: comprises 100 CHC patients who will receive placebo twice daily with food for an average of 12 weeks as a part of monotherapy lead-in phase followed by triple therapy, nitazoxanide 500 mg twice daily plus peginterferon alfa-2a (once weekly), and weight-based ribavirin (1000-1200 mg daily) for 48 weeks.
Other Name: Control group
Experimental: Nitazoxanide

• Group B: comprises 100 CHC patients who will receive oral Nitazoxanide 500 mg twice daily with food for an average of 12 weeks as a part of monotherapy lead-in phase followed by triple therapy, nitazoxanide 500 mg twice daily plus peginterferon alfa-2a (once weekly), and weight-based ribavirin (1000-1200 mg daily) for 48 weeks.

All patients in this group will have an HCV RNA within 3 months before initiation of therapy, in addition to ALT levels, CBC and other routine liver function tests.

Drug: Nitazoxanide
• Group B: comprises 100 chronic hepatitis patients who will receive oral Nitazoxanide 500 mg twice daily with food for an average of 12 weeks followed by the standard of care treatment, peginterferon Alfa 2a once weekly and weight-based ribavirin 1000 or 1200 mg/day (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses plus placebo twice daily for 48 weeks.
Other Names:
  • Alinia
  • Xerovirinc(Minapharm Pharmaceuticals)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 18 and <60.
  • Liver biopsy showing chronic hepatitis with significant fibrosis using Ishak scoring system.
  • Compensated liver disease; serum bilirubin < 1.5 mg/dl, INR no more than 1.5, serum albumin > 3.4, platelet count >75,000 mm, and no evidence of hepatic decompensation (hepatic encephalopathy or ascites).
  • Acceptable hematological and biochemical indices (hemoglobin 13g/dl for men and 12 g/dl for women; neutrophil count 1500/mm3 or more and serum creatinine <1.5 mg/dl.
  • Willing to be treated and to adhere to treatment requirements

Exclusion Criteria:

  • Major uncontrolled depressive illness.
  • Solid organ transplantation.
  • Autoimmune conditions, known to be exacerbated by peginterferon and ribavirin.
  • Untreated thyroid disease.
  • Pregnant or unwilling to comply with adequate contraception.
  • Severe concurrent medical disease such as severe hypertension, heart failure, significant coronary heart disease, poorly controlled diabetes, chronic obstructive pulmonary disease.
  • Known hypersensitivity to drugs used to treat HCV.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01197157

Locations
Egypt
National Liver Institute
Shebin El-Kom, Menoufiya, Egypt
Sponsors and Collaborators
National Liver Institute, Egypt
Investigators
Principal Investigator: Mohamed A Kohla, MD National Liver Institute, Menoufiya University, Egypt
Study Director: Hossam A Taha, MD National Liver Institute, Menoufiya University, Egypt
  More Information

No publications provided

Responsible Party: Mohamed Kohla, Lecturer of Hepatology, National Liver Institute, Egypt
ClinicalTrials.gov Identifier: NCT01197157     History of Changes
Other Study ID Numbers: NEAR trial
Study First Received: August 9, 2010
Last Updated: September 27, 2014
Health Authority: Egypt:National Liver Institute, menoufiya University.
Egypt:Science and Technology Development Fund.

Keywords provided by National Liver Institute, Egypt:
chronic hepatitis C
genotype 4
treatment naive patients
Egypt

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferon-alpha
Nitazoxanide
Peginterferon alfa-2a
Anti-Infective Agents
Antiparasitic Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014