Efficacy and Safety of the Combination Vitamin D (Vit D), With Pegylated Interferon Alpha-2b (PEG-IFN)/Ribavirin (RBV) in Egyptian Patients With Untreated Chronic Hepatitis C: A Phase III Randomized Open-label Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Proportion of patients with Sustained Virological Response (SVR).
研究概览
简要总结
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).
详细描述
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Method: Phase III, randomized, open-label superiority clinical trial, among Egyptian patients with chronic hepatitis C.
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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.
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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..
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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 F
- •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.
研究组 & 干预措施
Vitamin D
Vitamin D + Pegylated Interferon Alpha 2b + Ribavirin
干预措施: Vitamin D + Pegylated Interferon Alpha 2b + Ribavirin (Drug)
结局指标
主要结局
Proportion of patients with Sustained Virological Response (SVR).
时间窗: 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.
次要结局
- Rapid Virological Response (RVR)(4 Weeks after peg-IFN/RBV initiation)
- End of Treatment Response (ETR)(48 Weeks after peg-IFN/RBV initiation)
- Early Virological Response (EVR)(12 Weeks after peg-IFN/RBV initiation)
- 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))
- Evolution of FibroScan values between pre-inclusion and week 60(At Screening Visit 2 (S2) and at End of Follow-up (Week 60))