Vitamin D as an add-on Therapy With Pegylated Interferon and Ribavirin for Chronic Hepatitis c

Phase 3

• Conditions: Chronic Hepatitis c
• Interventions: Drug: pegylated interferon + ribavirin; Drug: vitamin D +pegylated interferon + ribavirin

• Registration Number: NCT01655966
• Lead Sponsor: Cairo University

Brief Summary

Chronic hepatitis C is endemic in Egypt with a high prevalence of the resistant genotype 4. Conventional standard of care treatment has modest response with only 50% sustained virologic response. Recent reports have suggested an augmented response with the addition of vitamin D. This is a prospective randomized trial to assess the effectiveness of adding vitamin D to standard of care for chronic hepatitis C genotype 4.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05
• Study First Submitted: 2012-07-31
• Study First Submitted QC: 2012-08-01
• Study First Posted: 2012-08-02
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-28
• Last Update Posted: 2014-01-29
• Primary Completion: 2014-02
• Study Completion: 2014-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Adult (male or female), 18 to 65 years of age, with chronic HCV infection
• Liver biopsy showing chronic hepatitis with significant fibrosis using Ishak scoring system
• Compensated liver disease; serum bilirubin < 1.5 mg/dl, INR 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 12.5g/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
• Proper contraception measure 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 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 or MELD score > 8

• Absolute neutrophil count < 1500 cells/mm3; platelet count < 135,000 cells/mm3; hemoglobin < 12 g/dL for women and < 12.5 g/dL for men; or serum creatinine concentration ≥ 1.5 times ULN

• 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

  • Subjects receiving vitamin D for any other medical condition.
  • Subjects with significant active rheumatologic or orthopaedic conditions.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care	pegylated interferon + ribavirin	Group A: comprises 40 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	vitamin D +pegylated interferon + ribavirin	Group B: comprises 40 treatment-naive chronic HCV patients who will receive oral vitamin D 1mcg once 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	72 weeks	Undetectable HCV-RNA 24 weeks after end of treatment.

Secondary Outcome Measures

Name	Time	Method
rapid virologic response	4 weeks	undetectable HCV-RNA 4 weeks after commencement of treatment
End-of-treatment response	48 weeks	undetectable HCV-RNA 48 weeks after commencement of treatment
Adverse events	72 weeks	Adverse events that could be reasonably and temporally associated with administration of drugs
early virologic response	12 weeks	Early virologic response: undetectable HCV-RNA 12 weeks after commencement of treatment.; Partial early virologic response: decrease of more than 2login HCV-RNA.; No early virologic response: increase, stationary or decreased less than 2log HCV-RNA.

Trial Locations

Locations (1)

National Railway Hospital Center; 🇪🇬 Cairo, Egypt