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

NCT01276756 | Completed Phase 2 Results DMC

• 1 other identifier: RAIL001
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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).

Secondary Outcomes (4)

• Rapid Virological Response

  28 - 33 days after start of Pegylated interferon and ribavirin

• Early Virological Response

  90 ± 7 days from the start of pegylated interferon and ribavirin

• End-of-treatment Response

  48 weeks +- 7 days after starting 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

Study Arms (2)

Standard of care

ACTIVE COMPARATOR

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; Drug: Ribavirin

Triple therapy

EXPERIMENTAL

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; Drug: Nitazoxanide; Drug: Ribavirin

Interventions

Pegylated interferon alfa-2a DRUG

Pegylated interferon 160ug once weekly 48 weeks

Also known as: Reiferon retard

Standard of care; Triple therapy

Nitazoxanide DRUG

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

Also known as: Xerovirin-C

Triple therapy

Ribavirin DRUG

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

Standard of care; Triple therapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Cairo University: lead
• Egyptian Railway Hospital: collaborator

Study Sites (1)

Cairo University

Cairo, Egypt

Location

Related Publications (1)

• 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.

  PMID: 23890273 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

peginterferon alfa-2a; nitazoxanide; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr. Hany Shehab
• Organization: Cairo University

h.shehab@drshehab.com

00201111111071

Study Officials

• Hany M Shehab, MD

  Cairo University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: January 12, 2011
• First Posted: January 13, 2011
• Study Start: December 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: May 3, 2013
• Results First Posted: May 3, 2013

Record last verified: 2013-03

Locations

EG (1)