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

Chronic Hepatitis c Clinical Trial

Official title:

Randomized Study for the Assessment of Nitazoxanide in the Treatment of Chronic Hepatitis C Genotype 4

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01276756
• Other study ID #: RAIL001
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 12, 2011
• Last updated: March 19, 2013
• Start date: December 2010
• Est. completion date: November 2012

Study information

• Verified date: March 2013
• Source: Cairo University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Ministry of Health and Population
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis c
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Pegylated interferon alfa-2a
Pegylated interferon 160ug once weekly 48 weeks
• Nitazoxanide
Nitazoxanide 500mg twice daily 4 weeks lead-in followed by triple therapy 48 weeks
• Ribavirin
Ribavirin (> 75kg:1200 mg, <75kg:1000mg daily)48 weeks

Locations

Country	Name	City	State
Egypt	Cairo University	Cairo

Sponsors (2)

Lead Sponsor	Collaborator
Cairo University	Egyptian Railway Hospital

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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).	No
Secondary	Rapid Virological Response	A rapid virologic response is defined as a negative HCV PCR 4 weeks after treatment	28 - 33 days after start of Pegylated interferon and ribavirin	No
Secondary	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	90 ± 7 days from the start of pegylated interferon and ribavirin	No
Secondary	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	48 weeks +- 7 days after starting pegylated interferon and ribavirin	No
Secondary	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.	throughout the period of treatment and up to 90 days after end of triple therapy	Yes