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

Phase 2

Completed

Conditions: Chronic Hepatitis c

Interventions: Drug: Pegylated interferon alfa-2a
Drug: Nitazoxanide
Drug: Ribavirin

Registration Number: NCT01276756

Lead Sponsor: Cairo University

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 100

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care	Pegylated interferon alfa-2a	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.
Triple therapy	Nitazoxanide	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.
Standard of care	Ribavirin	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.
Triple therapy	Pegylated interferon alfa-2a	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.
Triple therapy	Ribavirin	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.

Primary Outcome Measures

Name	Time	Method
Sustained Virologic Response	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).	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

Name	Time	Method
Early Virological Response	90 ± 7 days from the start of pegylated interferon and ribavirin	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
Rapid Virological Response	28 - 33 days after start of Pegylated interferon and ribavirin	A rapid virologic response is defined as a negative HCV PCR 4 weeks after treatment
End-of-treatment Response	48 weeks +- 7 days after starting pegylated interferon and ribavirin	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)	throughout the period of treatment and up to 90 days after end of triple therapy	The occurence of adverse events that could be linked temporally and reasonably to the administration of the tested drug.