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

This study has been completed.
Sponsor:
Collaborator:
Egyptian Railway Hospital
Information provided by (Responsible Party):
Hany Shehab, Cairo University
ClinicalTrials.gov Identifier:
NCT01276756
First received: January 12, 2011
Last updated: March 19, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis c
Drug: Pegylated interferon alfa-2a
Drug: Nitazoxanide
Drug: Ribavirin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Study for the Assessment of Nitazoxanide in the Treatment of Chronic Hepatitis C Genotype 4

Resource links provided by NLM:


Further study details as provided by Cairo University:

Primary Outcome Measures:
  • Sustained Virologic Response [ 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). ] [ Designated as safety issue: No ]
    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 [ Time Frame: 28 - 33 days after start of Pegylated interferon and ribavirin ] [ Designated as safety issue: No ]
    A rapid virologic response is defined as a negative HCV PCR 4 weeks after treatment

  • Early Virological Response [ Time Frame: 90 ± 7 days from the start of pegylated interferon and ribavirin ] [ Designated as safety issue: No ]

    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 [ Time Frame: 48 weeks +- 7 days after starting pegylated interferon and ribavirin ] [ Designated as safety issue: No ]
    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) [ Time Frame: throughout the period of treatment and up to 90 days after end of triple therapy ] [ Designated as safety issue: Yes ]
    The occurence of adverse events that could be linked temporally and reasonably to the administration of the tested drug.


Enrollment: 100
Study Start Date: December 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard of care
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.
Drug: Pegylated interferon alfa-2a
Pegylated interferon 160ug once weekly 48 weeks
Other Name: Reiferon retard
Drug: Ribavirin
Ribavirin (> 75kg:1200 mg, <75kg:1000mg daily)48 weeks
Other Name: Ribavirin
Experimental: Triple therapy
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.
Drug: Pegylated interferon alfa-2a
Pegylated interferon 160ug once weekly 48 weeks
Other Name: Reiferon retard
Drug: Nitazoxanide
Nitazoxanide 500mg twice daily 4 weeks lead-in followed by triple therapy 48 weeks
Other Name: Xerovirin-C
Drug: Ribavirin
Ribavirin (> 75kg:1200 mg, <75kg:1000mg daily)48 weeks
Other Name: Ribavirin

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01276756

Locations
Egypt
Cairo University
Cairo, Egypt
Sponsors and Collaborators
Cairo University
Egyptian Railway Hospital
Investigators
Principal Investigator: Hany M Shehab, MD Cairo University
  More Information

No publications provided by Cairo University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hany Shehab, Dr, Cairo University
ClinicalTrials.gov Identifier: NCT01276756     History of Changes
Other Study ID Numbers: RAIL001
Study First Received: January 12, 2011
Results First Received: January 30, 2013
Last Updated: March 19, 2013
Health Authority: Egypt: Ministry of Health and Population

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

ClinicalTrials.gov processed this record on July 22, 2014