search
Back to results

Efficacy of Nitazoxanide in the Treatment of Chronic Hepatitis C Virus (HCV)

Primary Purpose

Chronic Hepatitis c

Status
Completed
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
Pegylated interferon alfa-2a
Nitazoxanide
Ribavirin
Sponsored by
Cairo University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis c

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult (male or female), 18 to 65 years of age, with chronic HCV infection
  • BMI < 35
  • Liver biopsy showing chronic hepatitis with significant fibrosis using Ishak scoring system
  • Compensated liver disease; serum bilirubin < 1.5 mg/dl, INR (international normalized ratio) 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
  • Patients must be serum hepatitis B surface antigen (HBsAg) negative
  • Negative Antinuclear Antibodies (ANA) or titer of < 1:160
  • Serum positive for anti-HCV antibodies and HCV-RNA
  • Abdominal Ultrasound obtained within 3 months prior to entry in the study
  • Electrocardiogram for men aged > 40 years and for women aged > 50 years
  • Normal fundus examination
  • Ensure strict measures to avoid conception for both male and female participants by using a proper contraception measure all throughout the course of treatment and six months later
  • Female patients must not breast feed during therapy

Exclusion Criteria:

  • Patients who previously received interferon
  • HgbA1c > 7.5 (glycoslylated haemoglobin)or history of diabetes mellitus
  • BMI > 34
  • Women who are pregnant or breast-feeding
  • Males whose female partners are either pregnant or of child-bearing potential or not using birth control and are sexually active
  • Other causes of liver disease including autoimmune hepatitis
  • Transplant recipients receiving immune suppression therapy
  • Screening tests positive for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab or anti-HIV Ab
  • Decompensated cirrhosis, history of variceal bleeding, ascites, hepatic encephalopathy, CTP score > 6 (Child-Turcot-Pugh) or MELD score > 8
  • Absolute neutrophil count < 1500 cells/mm3; platelet count < 135,000 cells/mm3; hemoglobin < 12 g/dL for women and < 13 g/dL for men; or serum creatinine concentration ≥ 1.5 times ULN (upper limit of normal)
  • Hypothyroidism or hyperthyroidism not effectively treated with medication
  • Alcohol consumption of > 40 grams per day or an alcohol use pattern that will interfere with the study
  • History or other clinical evidence of significant or unstable cardiac disease
  • History or other clinical evidence of chronic pulmonary disease associated with functional impairment
  • Serious or severe bacterial infection(s)
  • History of severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization
  • History of uncontrolled severe seizure disorder
  • History of immunologically mediated disease requiring more than intermittent anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids
  • Patients with clinically significant retinal abnormalities
  • History of hypersensitivity or intolerance to nitazoxanide or any of the excipients comprising the nitazoxanide tablets, peginterferon alfa-2a injectable solution or ribavirin tablets

Sites / Locations

  • Cairo University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of care

Triple therapy

Arm Description

Group A: comprises 50 treatment-naive chronic hepatitis c patients who will receive the standard of care treatment: peginterferon Alfa 2a 160 ug once weekly and weight-based ribavirin 1000 or 1200 mg/day (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses for 48 weeks.

Group B: comprises 50 treatment-naive chronic HCV patients who will receive oral Nitazoxanide 500 mg twice daily for 4 weeks (lead-in phase) followed by triple therapy, nitazoxanide 500 mg twice daily plus peginterferon alfa-2a (160ug once weekly) and weight-based ribavirin 1000-1200 mg daily (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses for 48 weeks.

Outcomes

Primary Outcome Measures

Sustained Virologic Response
sustained virological response is defined as a negative HCV PCR at 180 days after the end of treatment (End of treatment being at 48 weeks for Group A, 52 weeks for Group B). For any patient who stopped treatment prematurely (e.g. due to adverse events) SVR was defined as a negative HCV PCR (polymerase chain reaction) at 180 days after the last dose of all medications (interferon, ribavirin and nitazoxanide)

Secondary Outcome Measures

Rapid Virological Response
A rapid virologic response is defined as a negative HCV PCR 4 weeks after treatment
Early Virological Response
A complete early virologic response is defined as a negative HCV PCR 90 days after the start of pegylated interferon. A partial early virologic response is defined as a decrease of 2 or more log in HCV PCR at 90 days after the start of pegylated interferon
End-of-treatment Response
An end-of-treatment response is defined as a negative HCV PCR at 48 weeks after the start of pegylated interferon and ribavirin
Safety of Nitazoxanide (Number of Participants Experiencing Adverse Events)
The occurence of adverse events that could be linked temporally and reasonably to the administration of the tested drug.

Full Information

First Posted
January 12, 2011
Last Updated
March 19, 2013
Sponsor
Cairo University
Collaborators
Egyptian Railway Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT01276756
Brief Title
Efficacy of Nitazoxanide in the Treatment of Chronic Hepatitis C Virus (HCV)
Official Title
Randomized Study for the Assessment of Nitazoxanide in the Treatment of Chronic Hepatitis C Genotype 4
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cairo University
Collaborators
Egyptian Railway Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Chronic hepatitis C has become an endemic disease in Egypt with a rising prevalence (genotype 4), worldwide it also poses a significant health burden. To date standard of care treatment (pegylated interferon and ribavirin) give modest results with a sustained virological response (SVR) of about 50%. Several pharmaceutical and herbal agents have been used with an aim to improve current results. Recent reports have suggested an increased SVR with the addition of Nitazoxanide to standard of care. The results are preliminary and need to be confirmed. This is a randomized trial to assess the efficacy of nitazoxanide added to standard of care compared to standard of care alone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis c

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of care
Arm Type
Active Comparator
Arm Description
Group A: comprises 50 treatment-naive chronic hepatitis c patients who will receive the standard of care treatment: peginterferon Alfa 2a 160 ug once weekly and weight-based ribavirin 1000 or 1200 mg/day (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses for 48 weeks.
Arm Title
Triple therapy
Arm Type
Experimental
Arm Description
Group B: comprises 50 treatment-naive chronic HCV patients who will receive oral Nitazoxanide 500 mg twice daily for 4 weeks (lead-in phase) followed by triple therapy, nitazoxanide 500 mg twice daily plus peginterferon alfa-2a (160ug once weekly) and weight-based ribavirin 1000-1200 mg daily (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses for 48 weeks.
Intervention Type
Drug
Intervention Name(s)
Pegylated interferon alfa-2a
Other Intervention Name(s)
Reiferon retard
Intervention Description
Pegylated interferon 160ug once weekly 48 weeks
Intervention Type
Drug
Intervention Name(s)
Nitazoxanide
Other Intervention Name(s)
Xerovirin-C
Intervention Description
Nitazoxanide 500mg twice daily 4 weeks lead-in followed by triple therapy 48 weeks
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Description
Ribavirin (> 75kg:1200 mg, <75kg:1000mg daily)48 weeks
Primary Outcome Measure Information:
Title
Sustained Virologic Response
Description
sustained virological response is defined as a negative HCV PCR at 180 days after the end of treatment (End of treatment being at 48 weeks for Group A, 52 weeks for Group B). For any patient who stopped treatment prematurely (e.g. due to adverse events) SVR was defined as a negative HCV PCR (polymerase chain reaction) at 180 days after the last dose of all medications (interferon, ribavirin and nitazoxanide)
Time Frame
180 days (+- 7 days) after the end of treatment. (48 weeks for Group A, 52 weeks for Group B, or after the last dose of treatment for patients who stopped prematurely).
Secondary Outcome Measure Information:
Title
Rapid Virological Response
Description
A rapid virologic response is defined as a negative HCV PCR 4 weeks after treatment
Time Frame
28 - 33 days after start of Pegylated interferon and ribavirin
Title
Early Virological Response
Description
A complete early virologic response is defined as a negative HCV PCR 90 days after the start of pegylated interferon. A partial early virologic response is defined as a decrease of 2 or more log in HCV PCR at 90 days after the start of pegylated interferon
Time Frame
90 ± 7 days from the start of pegylated interferon and ribavirin
Title
End-of-treatment Response
Description
An end-of-treatment response is defined as a negative HCV PCR at 48 weeks after the start of pegylated interferon and ribavirin
Time Frame
48 weeks +- 7 days after starting pegylated interferon and ribavirin
Title
Safety of Nitazoxanide (Number of Participants Experiencing Adverse Events)
Description
The occurence of adverse events that could be linked temporally and reasonably to the administration of the tested drug.
Time Frame
throughout the period of treatment and up to 90 days after end of triple therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult (male or female), 18 to 65 years of age, with chronic HCV infection BMI < 35 Liver biopsy showing chronic hepatitis with significant fibrosis using Ishak scoring system Compensated liver disease; serum bilirubin < 1.5 mg/dl, INR (international normalized ratio) 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 Patients must be serum hepatitis B surface antigen (HBsAg) negative Negative Antinuclear Antibodies (ANA) or titer of < 1:160 Serum positive for anti-HCV antibodies and HCV-RNA Abdominal Ultrasound obtained within 3 months prior to entry in the study Electrocardiogram for men aged > 40 years and for women aged > 50 years Normal fundus examination Ensure strict measures to avoid conception for both male and female participants by using a proper contraception measure all throughout the course of treatment and six months later Female patients must not breast feed during therapy Exclusion Criteria: Patients who previously received interferon HgbA1c > 7.5 (glycoslylated haemoglobin)or history of diabetes mellitus BMI > 34 Women who are pregnant or breast-feeding Males whose female partners are either pregnant or of child-bearing potential or not using birth control and are sexually active Other causes of liver disease including autoimmune hepatitis Transplant recipients receiving immune suppression therapy Screening tests positive for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab or anti-HIV Ab Decompensated cirrhosis, history of variceal bleeding, ascites, hepatic encephalopathy, CTP score > 6 (Child-Turcot-Pugh) or MELD score > 8 Absolute neutrophil count < 1500 cells/mm3; platelet count < 135,000 cells/mm3; hemoglobin < 12 g/dL for women and < 13 g/dL for men; or serum creatinine concentration ≥ 1.5 times ULN (upper limit of normal) Hypothyroidism or hyperthyroidism not effectively treated with medication Alcohol consumption of > 40 grams per day or an alcohol use pattern that will interfere with the study History or other clinical evidence of significant or unstable cardiac disease History or other clinical evidence of chronic pulmonary disease associated with functional impairment Serious or severe bacterial infection(s) History of severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization History of uncontrolled severe seizure disorder History of immunologically mediated disease requiring more than intermittent anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids Patients with clinically significant retinal abnormalities History of hypersensitivity or intolerance to nitazoxanide or any of the excipients comprising the nitazoxanide tablets, peginterferon alfa-2a injectable solution or ribavirin tablets
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hany M Shehab, MD
Organizational Affiliation
Cairo University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cairo University
City
Cairo
Country
Egypt

12. IPD Sharing Statement

Citations:
PubMed Identifier
23890273
Citation
Shehab HM, Elbaz TM, Deraz DM. Nitazoxanide plus pegylated interferon and ribavirin in the treatment of genotype 4 chronic hepatitis C, a randomized controlled trial. Liver Int. 2014 Feb;34(2):259-65. doi: 10.1111/liv.12267. Epub 2013 Jul 24.
Results Reference
derived

Learn more about this trial

Efficacy of Nitazoxanide in the Treatment of Chronic Hepatitis C Virus (HCV)

We'll reach out to this number within 24 hrs