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

NCT ID: NCT01276756

Last Updated: 2013-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2012-11-30

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.

Conditions

Chronic Hepatitis c

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Pegylated interferon alfa-2a

Intervention Type: DRUG

Pegylated interferon 160ug once weekly 48 weeks

Ribavirin

Intervention Type: DRUG

Ribavirin (\> 75kg:1200 mg, \<75kg:1000mg daily)48 weeks

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.

Group Type: EXPERIMENTAL

Pegylated interferon alfa-2a

Intervention Type: DRUG

Pegylated interferon 160ug once weekly 48 weeks

Nitazoxanide

Intervention Type: DRUG

Nitazoxanide 500mg twice daily 4 weeks lead-in followed by triple therapy 48 weeks

Ribavirin

Intervention Type: DRUG

Ribavirin (\> 75kg:1200 mg, \<75kg:1000mg daily)48 weeks

Interventions

Pegylated interferon alfa-2a

Pegylated interferon 160ug once weekly 48 weeks

Intervention Type: DRUG

Nitazoxanide

Nitazoxanide 500mg twice daily 4 weeks lead-in followed by triple therapy 48 weeks

Intervention Type: DRUG

Ribavirin

Ribavirin (\> 75kg:1200 mg, \<75kg:1000mg daily)48 weeks

Intervention Type: DRUG

Other Intervention Names

Reiferon retard; Xerovirin-C

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Egyptian Railway Hospital

OTHER

Sponsor Role: collaborator

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Hany Shehab

Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hany M Shehab, MD

Role: PRINCIPAL_INVESTIGATOR

Cairo University

Locations

Cairo University

Cairo, , Egypt

Countries

Egypt

References

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.

Reference Type: DERIVED

PMID: 23890273 (View on PubMed)

Other Identifiers

RAIL001

Identifier Type: -

Identifier Source: org_study_id