Safety and Efficacy of Hansenula-Derived Pegylated-Interferon Alpha-2a and Ribavirin Customized Combination Therapy in Egyptian Children With Chronic Hepatitis C Infection
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 3
- 主要终点
- To study the safety of Hansenula-Derived Pegylated-Interferon Alpha-2a (Reiferon retard) in attaining sustained virological response in children with chronic hepatitis C virus infection
研究概览
简要总结
Egypt has the highest prevalence of hepatitis C virus infection in adults (up to 20%) and children (up to 5.5%). The major genotype (90%) is type 4. Pegylated interferon-alpha-2a or -2b and ribavirin have been used in small numbers of hepatitis C virus-infected children with sustained virological response being higher in genotypes 2 and 3 than in genotypes 1 and 4. Genotype 4 is has been described as difficult-to-treat genotype. Several attempts to modify treatment protocols have been tried in adults in an attempt to achieve higher rates of sustained virological response. Shortening injection interval and/or treatment duration prolongation have been tried with variable outcome reports.
A novel Hansenula- derived pegylated interferon alpha 2a: 20 Kilo dalton (Reiferon Retard) has been used over the last 4 years in the Egyptian market.
We aimed to investigate the safety and efficacy of Reiferon retard plus ribavirin customized regimen in hepatitis C virus-RNA seropositive Egyptian children. Forty six children with chronic hepatitis C virus aged 3-19 years were selected from 3 hepatic tertiary centers.
Clinical and laboratory evaluation were undertaken. Quantitative polymerase chain reaction (PCR) for HCV-RNA was done before starting treatment, at 4, 12, 24, 48, 72 weeks during treatment and 6 months after stoppage of treatment. All patients were assigned to receive a weekly subcutaneous injection of pegylated interferon alpha 2-a ( Reiferon Retard) plus oral Ribavirin daily for 12 weeks ,then cases were divided according to PCR results into 2 groups.
Group I: Patients who continued treatment on weekly basis: this group included patients who had negative PCR at week 12 as well those who had positive PCR without any change in viremia. Group II: Patients who continued treatment on a 5- days schedule: this group included patients who had any decrease in viremia at week 12.
Patients who were PCR-negative at week 48 and had at least one PCR-positive test during therapy were assigned to have an extended treatment course of 6 months duration.
The occurrence of adverse effects was assessed during treatment and follow up
详细描述
hepatitis C virus is a major health problem, not only in adults but also in the pediatric age group. In Egypt, the prevalent genotype is the difficult-to-treat genotype 4. Attempts are being made to improve the treatment outcomes. In the current study we aim to investigate the effect of customized pegylated interferon-alpha-2a plus ribavirin in children with chronic hepatitis C virus. For that, 46 children with chronic hepatitis C virus were recruited from three tertiary Pediatric Hepatology centers. All were assigned to receive weekly subcutaneous pegylated interferon-alpha-2a plus daily ribavirin for 12 weeks. At this point, the study population was divided into two arms. Arm 1 included those who became hepatitis C virus-RNA negative by polymerase chain reaction and those who showed no change of viremia or a decrease of less than 1 log. This group continued treatment on weekly bases for 48 weeks, even those who are hepatitis C virus-RNA positive. Arm 2; included patients who had a decrease in viremia more than one log of pre-treatment viremia level. For those patients, injection interval was shortened to every 5-day for a completion period of 48 weeks. Patients from either group who were polymerase chain reaction-negative at week 48, but had at least one polymerase chain reaction-positive test during therapy, were assigned to have an extended treatment course up to 72 weeks.
So the first customization was,
- prolongation of treatment duration for up to 48 weeks regardless response type
- Shortening injection interval in some patients to every 5-day injection
- The third customization was the prolongation of treatment for extra 6 months, i.e. up tp 72 weeks in some patients.
The occurrence of adverse effects, virological and biochemical responses were assessed during treatment and follow up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •children aged 3-19 years
- •compensated chronic HCV infection (HCV-RNA positive by PCR for more than 6 months)
- •whose hemoglobin was ≥10 g/dL
- •neutrophilic count > 1500/mm3
- •platelet count > 75,000/mm3
- •normal random blood sugar
- •normal serum creatinine
- •normal serum ferritin
- •normal thyroid function tests
- •normal lipid profile
- •no other causes of liver disease (autoimmune hepatitis, Wilson disease, alpha one antitrypsin deficiency nor hepatitis B virus infection).
- •Liver biopsy was mandatory for enrollment
排除标准
- •decompensated cirrhosis
- •any other cause of liver disease associating HCV infection
- •body mass index ≥ 95 percentile
- •severe psychiatric conditions
- •uncontrolled seizure disorder
- •decompensated cardiovascular disease, renal insufficiency
- •evidence of retinopathy
- •decompensated thyroid disease
- •hemoglobinopathy
- •immunologically mediated diseases or any other chronic illness requiring long term immunosuppressive drugs
- •previous interferon therapy within one year of enrollment
研究组 & 干预措施
Reiferon R weekly plus ribavirin
patients who continued treatment on weekly basis (7-day schedule). This group included patients who were HCV-RNA negative at week 12 and those who had < 1 log decrease in HCV-RNA viremia
干预措施: Reiferon R (Drug)
Reiferon R weekly plus ribavirin
patients who continued treatment on weekly basis (7-day schedule). This group included patients who were HCV-RNA negative at week 12 and those who had < 1 log decrease in HCV-RNA viremia
干预措施: Ribavirin (Drug)
Reiferon R (every 5-day) plus ribavirin
patients who continued treatment on a 5-day schedule. This group included patients who had ≥ 1 log decrease in viremia (compared to pre-treatment level) at week 12
干预措施: Reiferon R (Drug)
Reiferon R (every 5-day) plus ribavirin
patients who continued treatment on a 5-day schedule. This group included patients who had ≥ 1 log decrease in viremia (compared to pre-treatment level) at week 12
干预措施: Ribavirin (Drug)
结局指标
主要结局
To study the safety of Hansenula-Derived Pegylated-Interferon Alpha-2a (Reiferon retard) in attaining sustained virological response in children with chronic hepatitis C virus infection
时间窗: 48 weeks
The efficacy and Safety was assessed during the 48 weeks of therapy, patients were monitored clinically, laboratory for the appearance of any side effects
次要结局
- Efficacy of treatment customization on the outcome(96 weeks)
研究者
Mostafa M. Sira
Associate Professor of Pediatric Hepatology
National Liver Institute, Egypt