Clinical trial NCT01276756: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Chronic Hepatitis c
Lead sponsor: Cairo University
Sponsor class: OTHER
Collaborators: name: Egyptian Railway Hospital
First posted: 2011-01-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Sustained Virologic Response
timeFrame: 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 outcomes:
measure: Rapid Virological Response
timeFrame: 28 - 33 days after start of Pegylated interferon and ribavirin
measure: Early Virological Response
timeFrame: 90 ± 7 days from the start of pegylated interferon and ribavirin
measure: End-of-treatment Response
timeFrame: 48 weeks +- 7 days after starting pegylated interferon and ribavirin
measure: Safety of Nitazoxanide (Number of Participants Experiencing Adverse Events)
timeFrame: throughout the period of treatment and up to 90 days after end of triple therapy
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Cairo University
Study officials:
affiliation: Cairo University
name: Hany M Shehab, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.