Efficacy and Safety of the Combination Vitamin D With Standard of Care in Egyptian Patients With Untreated Chronic Hepatitis C
- Conditions
- Chronic Hepatitis C
- Interventions
- Drug: Vitamin D + Pegylated Interferon Alpha 2b + Ribavirin
- Registration Number
- NCT02099604
- Lead Sponsor
- ANRS, Emerging Infectious Diseases
- Brief Summary
The purpose of this study is to show the superiority of a 4 weeks lead-in phase of Vitamin D followed by a 48 weeks combination of Vitamin D with PEG-IFN plus RBV in comparison with standard PEG-IFN + RBV in untreated Egyptian patients with chronic hepatitis C, on the sustained virological response (SVR) at 3 months after end of treatment (week 60).
- Detailed Description
- Method: Phase III, randomized, open-label superiority clinical trial, among Egyptian patients with chronic hepatitis C.
- Treatment strategy: Vitamin D Arm: Vitamin D over a 4 weeks lead-in phase followed by Vitamin D in combination with PEG-INF plus RBV during 48 weeks. Standard of Care Arm: PEG-INF plus RBV during 48 weeks.
- Main outcome: Proportion of patients with Sustained Virological Response (SVR) as defined by HCV RNA below the detection limit based on quantitative PCR 12 weeks after stopping treatment.
* Sample Size: 520 patients (260 per arm)
* Enrollment period: 12 months
* Patient's participation duration: 62 weeks (SOC Arm), 66 weeks (Vit-D Arm)
* Statistical analysis:
The superiority of the vitamin D arm will be tested against the standard PEG IFN + RBV combination. 260 patients in each arm will give 80% power to document a 12% difference in the SVR rates between the experimental (Vitamin D) and the control (standard treatment) arms..
A futility analysis is planned for this study, in order to be able to interrupt the trial prematurely in case preliminary results show a lack of efficacy of vitamin D.
This analysis will be performed on half of the patients, thus 260 patients (130 patients per arm), on a week 12/14 week criterion (HCV RNA viral load at W12/W14).
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Common with National Program for Viral Hepatitis
- Age: 18 years to 60 years
- Positive HCV antibodies using a third generation test
- Detectable HCV RNA by PCR
- Liver biopsy showing chronic hepatitis with either a METAVIR score F1 with elevated liver enzymes or scores F2/F3
- Naïve to treatment with PEG-IFN and RBV
- HBs antigen negative
- Prothrombin time ≥60 %, normal bilirubin, alpha-foeto protein < 3*normal range of the laboratory, anti-nuclear antibodies<1/160 Effective contraception during the treatment period; no breast-feeding
Specific to the trial
- Prior approval from the Ministry of Health to be treated as part of the National Program with allocation to Peg-IFN α2b treatment
- Living <100 km from Cairo and able to come to the centre every week for the treatment
- Signed informed consent and willingness to participate in the trial
- Naïve to treatment with vitamin D (received vitamin D less than 30 consecutive days in the 3 months preceding inclusion)
- Biopsy slide validated by NHTMRI pathologist
Common with National program for Viral Hepatitis
- Serious co-morbid conditions such as severe hypertension, heart failure, significant coronary heart disease, poorly controlled diabetes (HbA1C>8%) , chronic obstructive pulmonary disease
- Major uncontrolled depressive illness
- Solid transplant organ (renal, heart, or lung)
- Untreated thyroid disease
- History of previous anti-HCV therapy
- Body mass index (BMI) greater than 30 kg/m²
- Known human immunodeficiency virus (HIV) coinfection: although HIV testing will not be proposed or done, patients with known HIV coinfection will not be included in the trial
- Anti-HCV therapy contraindications:
- hypersensitivity to one of the two drugs (PEG-IFN, RBV)
- pregnancy or unwilling to comply with adequate contraception
- breast-feeding
- neutropenia (<1500/mm3)
- anaemia (<11g/dL for women ; <12g/dL for men)
- thrombocytopenia (<100,000/mm3)
- elevated creatinin (>1.5mg/dL)
- concomitant liver disease other than hepatitis C (immuno-active chronic hepatitis B, autoimmune hepatitis, alcoholic liver disease, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson disease)
- liver biopsy showing severe steatosis (>66%) and steatohepatitis; decompensated cirrhosis (Child Pugh>A); hepatocellular carcinoma, METAVIR score F4.
- TSH>5 mU/L
Specific to the trial
- Patients allocated to Peg-IFN alpha 2a treatment
- Hypersensitivity to vitamin D
- Vitamin D contraindications:
- hypercalcaemia (fasting calcaemia >105 mg/L or 2.62 mmol/L)
- ratio calciuria / creatininuria (fasting ratio >1 mmol Ca/mmol creatinin)
- hyperphosphatemia (>1.5 mmol/L)
- calcium lithiasis
- patients being treated with thiazide diuretics (risk of hypercalcaemia with vitamin D treatment)
- patients being treated with glucocorticoïds (decrease in vitamin D efficacy)
- postmenopausal women treated by vitamin D and calcium for osteoporosis
- Treatment by vitamin D more than 30 consecutive days in the 3 months preceding inclusion in the trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vitamin D Vitamin D + Pegylated Interferon Alpha 2b + Ribavirin Vitamin D + Pegylated Interferon Alpha 2b + Ribavirin
- Primary Outcome Measures
Name Time Method Proportion of patients with Sustained Virological Response (SVR). 60 Weeks after peg-IFN/RBV initiation Proportion of patients with Sustained Virological Response (SVR) as defined by HCV RNA below the detection limit based on quantitative PCR 12 weeks after stopping treatment.
- Secondary Outcome Measures
Name Time Method Rapid Virological Response (RVR) 4 Weeks after peg-IFN/RBV initiation HCV RNA at 4 weeks post initiation of combination therapy (PEG IFN + RBV)
End of Treatment Response (ETR) 48 Weeks after peg-IFN/RBV initiation HCV RNA at end of treatment (week 48)
Early Virological Response (EVR) 12 Weeks after peg-IFN/RBV initiation HCV RNA at 12 weeks post initiation of combination therapy
Normalization of ALT during treatment and 12 weeks after the end of treatment From 2 Weeks after peg-IFN/RBV initiation to End of Follow-up (Week 60) Incidence of serious adverse events (SAE) grade 3 and 4 (ANRS scale) From Lead-in phase (Week -4) to End of Follow-up (Week 60) incidence of SAE leading to dosage reduction or treatment cessation, percentage of patients treated by EPO and G-CSF
Evolution of FibroScan values between pre-inclusion and week 60 At Screening Visit 2 (S2) and at End of Follow-up (Week 60)
Trial Locations
- Locations (1)
NHTMRI
🇪🇬Cairo, Egypt