Study of the Impact of Nitazoxanide on Chronic Hepatitis Patients

NCT01197157 | Completed Phase 2 DMC

• 1 other identifier: NEAR trial
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatitis C

Keywords

chronic hepatitis C; genotype 4; treatment naive patients; Egypt

Outcome Measures

Primary Outcomes (1)

• Assessment of efficacy of Nitazoxanide as an add-on therapy in terms of achieving a sustained virologic response

  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.

  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)

Secondary Outcomes (5)

• assessment of rapid virologic response

  28-35 days from the start of triple therapy

• Assessment of early virologic response

  90 ± 7 days from the start of triple therapy

• Assessment of end-of-treatment response

  48± one week from the start of triple therapy

• Safety of Nitazoxanide

  Throughout the study and up to 90 days after the end of triple therapy

• Assessment of the efficacy of Nitazoxanide monotherapy following the lead-in phase

  90± 7 days from the start of the lead_in phase

Study Arms (2)

placebo

PLACEBO COMPARATOR

• 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

Nitazoxanide

EXPERIMENTAL

• 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

Interventions

Placebo DRUG

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.

Also known as: Control group

placebo

Nitazoxanide DRUG

• 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.

Also known as: Alinia, Xerovirinc(Minapharm Pharmaceuticals)

Nitazoxanide

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Liver Institute, Egypt: lead

Study Sites (1)

National Liver Institute

Shebin El-Kom, Monufia Governorate, Egypt

Location

MeSH Terms

Conditions

Hepatitis C; Hepatitis C, Chronic

Interventions

Control Groups; nitazoxanide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Mohamed A Kohla, MD

  National Liver Institute, Menoufiya University, Egypt

  PRINCIPAL INVESTIGATOR

• Hossam A Taha, MD

  National Liver Institute, Menoufiya University, Egypt

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Hepatology

Study Record Dates

• First Submitted: August 9, 2010
• First Posted: September 9, 2010
• Study Start: September 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: September 30, 2014

Record last verified: 2014-09

Locations

EG (1)