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

Cairo University (CU)

Status and phase: Unknown; Phase 3

Conditions: Chronic Hepatitis c

Treatments: Drug: pegylated interferon + ribavirin; Drug: vitamin D +pegylated interferon + ribavirin

Study type: Interventional

Funder types: Other

Identifiers

NCT01655966

RAIL002

Details and patient eligibility

About

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.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Standard of care

Active Comparator group

Description:

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.

Treatment:

Drug: pegylated interferon + ribavirin

Triple therapy

Experimental group

Description:

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.

Treatment:

Drug: vitamin D +pegylated interferon + ribavirin