IL28B Polymorphism, Sustained Virologic Response
Conditions
Keywords
reducing dose of peginterferon, chronic hepatitis c, Koreans, IL28B polymorphism
Brief summary
1. Randomized controlled multicenter study 2. The response of reducing dose of peginterferon alfa-2a in Koreans with chronic hepatitis C genotype 1 3. IL28B polymorphism in Koreans with CHC
Detailed description
The virologic response of Koreans to combination therapy for chronic hepatitis C is similar to non-Asians; however, dose modification occurs more frequently in Koreans. -When we evaluated the rates of peginterferon α-2a and ribavirin dose modifications and their effect on the virologic response in Koreans, we suggested that using at least 80% of the peginterferon α-2a dose in Koreans not only maintains SVR but also reduces drug side effects during the entire treatment period and a lower dose of ribavirin may be as efficacious as a standard dose(Korean J Intern Med 2009;24:203-211). So we investigate whether the group of 80% use dosage of peginterferon alfa-2a did not show inferior response rather than that of 100 % use dosage group and minimize the adverse events. There are recently reports that Koreans have favorable IL28B SNP for CHC treatment. -We investigate the IL28B polymorphism in Koreans with CHC and this result can effect on the SVR depending on the dosage of peginterferon alfa 2a
Interventions
DRUGpeginterferon alfa 2a (pegasys)
dosage form; 180ug/week during first 12 weeks and then 135 ug/week during 36 weeks otherwise unremarkable
DRUGpeginterferon alfa-2a (pegasys)
These patients would be treated with standard dose 180ug /week for 48 weeks. In general, the patient with CHC genotype 1is guided with treatment with pegasys 180ug /week and ribavirin 1000-1200 mg/day for 48 weeks. We do not make intervention of ribavirin dose.
Sponsors
Ulsan University Hospital
National Health Insurance Service Ilsan Hospital
Inje University
Soonchunhyang University Hospital
Yonsei University
Chungnam National University
Keimyung University
Kyungpook National University Hospital
Konyang University Hospital
Inha University Hospital
Hallym University Medical Center
The Catholic University of Korea
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* chronic hepatitis C (anti HCV+, HCV RNA +) * Genotype 1 * over 18 year-old * Pregnancy test negative if women of childbearing age
Exclusion criteria
* pregnant women or breast feeding women * systemic chemotherapy or steroid therapy before 6 months of trial * Coinfection with HAV, HBV, and HIV * Other liver disease such as hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxic hepatitis * Hepatocellular carcinoma * Evidence of decompensation such as variceal bleeding,ascites, encephalopathy * ANC less than 1500, platelet less than 90k * Cr more than 1.5 of UNL * Severe psychiatric problem * Poorly controlled thyroid disease * Severe retinopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virologic Response Depending on the Dosage of Peginterferon Alfa 2a | post treatment 24 weeks | We investigate whether the SVR between 100% and 80% group of peginterferon alfa 2a is not different. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IL28B Polymorphism Effect on SVR | post treatment 24 weeks | We additionally investigate the IL28B polymorphism and this result can effect on the SVR depending on dosage of peginterferon alfa-2a. |
Countries
South Korea
Participant flow
Recruitment details
enrollment date : 2009-2011 recruitment period : 2009-2012 type location: 14 university hospital
Pre-assignment details
no excluded patients before assignment to groups
Participants by arm
| Arm | Count |
|---|---|
| 100% Dosage Group of Peginterferon Alfa 2a These group patients would be treated with standard dose 180 ug/week for 48 weeks.
peginterferon alfa-2a (pegasys) : These patients would be treated with standard dose 180ug /week for 48 weeks.
In general, the patient with CHC genotype 1is guided with treatment with pegasys 180ug /week and ribavirin 1000-1200 mg/day for 48 weeks. We do not make intervention of ribavirin dose. | 92 |
| 80% Dosage Group of Peginterferon Alfa 2a This group patients will treated the same full dose (180ug/week) of peginterferon alfa 2a during the first 12 weeks and then reduce the 75% dose (135ug/week) of peginterferon alfa 2a during remnant 36 weeks. At a result, these patients treated with 80% dosage of originally prescribed peginterferon alfa-2a for standard 48 weeks of treatment.
peginterferon alfa 2a (pegasys) : dosage form; 180ug/week during first 12 weeks and then 135 ug/week during 36 weeks otherwise unremarkable | 86 |
| Total | 178 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 8 |
| Overall Study | Lack of Efficacy | 7 | 5 |
| Overall Study | Withdrawal by Subject | 12 | 13 |
Baseline characteristics
| Characteristic | Total | 80% Dosage Group of Peginterferon Alfa 2a | 100% Dosage Group of Peginterferon Alfa 2a |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 5 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 169 Participants | 81 Participants | 88 Participants |
| Age Continuous | 48.6 years STANDARD_DEVIATION 11 | 48.7 years STANDARD_DEVIATION 11.5 | 48.5 years STANDARD_DEVIATION 10.6 |
| Region of Enrollment Korea, Republic of | 178 participants | 86 participants | 92 participants |
| Sex: Female, Male Female | 87 Participants | 45 Participants | 42 Participants |
| Sex: Female, Male Male | 91 Participants | 41 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 92 | 49 / 86 |
| serious Total, serious adverse events | 0 / 92 | 0 / 86 |
Outcome results
Primary
Sustained Virologic Response Depending on the Dosage of Peginterferon Alfa 2a
We investigate whether the SVR between 100% and 80% group of peginterferon alfa 2a is not different.
Time frame: post treatment 24 weeks
Population: We present the result of intention-to-treat analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100% Dosage Group of Peginterferon Alfa 2a | Sustained Virologic Response Depending on the Dosage of Peginterferon Alfa 2a | 52 participants who achieved SVR |
| 80% Dosage Group of Peginterferon Alfa 2a | Sustained Virologic Response Depending on the Dosage of Peginterferon Alfa 2a | 44 participants who achieved SVR |
Secondary
IL28B Polymorphism Effect on SVR
We additionally investigate the IL28B polymorphism and this result can effect on the SVR depending on dosage of peginterferon alfa-2a.
Time frame: post treatment 24 weeks
Population: The patients who agreed to check the genotype were analysed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100% Dosage Group of Peginterferon Alfa 2a | IL28B Polymorphism Effect on SVR | 71.9 percentage of SVR |
| 80% Dosage Group of Peginterferon Alfa 2a | IL28B Polymorphism Effect on SVR | 33.3 percentage of SVR |