Patterns of Early Hepatitis C Virus Decline Predict the Outcome of Interferon Therapy (sIFN-pred1)
Recruitment status was Active, not recruiting
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Study of Parameters of Early Hepatitis C Virus Dynamics for Predicting the Outcome of Standard Interferon Therapy With Chinese Cohort|
- Blood HCV RNA Copies [ Time Frame: 0h,8h,10h,12h,18h,24h,37h,43h,3d,7d,2w,4w,6w,12w,24w,48w ] [ Designated as safety issue: No ]Blood HCV RNA copies were assayed with Roche - COBAS® AmpliPrep/COBAS® TaqMan® HCV Test.
- IL-28B polymorphism [ Time Frame: Baseline ] [ Designated as safety issue: No ]IL28 gene polymorphism,rs8099917,rs12979860,etc
- Microarray Analysis of PBMC Gene Expression [ Time Frame: Baseline,8h,18h,3d ] [ Designated as safety issue: No ]During the first 3 days, blood samples are collected for PBMC separation and microarray analysis.
- HCV genotype [ Time Frame: Baseline ] [ Designated as safety issue: No ]HCV NS5A is cloned into T vector and sequenced for evolutionary analysis.
- Blood Anti-HCV,HBV Antibody [ Time Frame: Baseline ] [ Designated as safety issue: No ]Co-infection status are analyzed.
- HCV genome sequencing [ Time Frame: 0h,8h,10h,12h,18h,24h,37h,43h,3d ] [ Designated as safety issue: No ]Deep sequencing is used for blood serum HCV genome analysis.
- Alanine Aminotransferase (ALT) and Aspartate transaminase (AST) [ Time Frame: Baseline,4w,6w,12w,24w,48w ] [ Designated as safety issue: No ]ALT AST are assayed to detect the hepatic function.
- Fibrosis stage [ Time Frame: Baseline,4w,12w,24w,48w ] [ Designated as safety issue: No ]Fibrosis is analyzed with Fibroscan.
- Regular blood test [ Time Frame: Baseline,4w,12w,24w,48w ] [ Designated as safety issue: Yes ]The distribution and absolute count of the different types of blood cells are assayed.
- Electrocardiography [ Time Frame: Baseline,4w,12w,24w,48w ] [ Designated as safety issue: Yes ]Electrocardiography is taken to avoid severe side effects.
- Alcohol ,smoking condition [ Time Frame: Baseline,4w,12w,24w,48w ] [ Designated as safety issue: No ]Patients are asked whether they take alcohol or smoke cigarettes during the therapy period.
- Drug abuse history [ Time Frame: Baseline ] [ Designated as safety issue: No ]Patients will be asked about their drug usage history.
Biospecimen Retention: Samples With DNA
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||December 2011|
|Estimated Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Interferon and ribavirin
All the patients followed the standard treatment protocol.
Drug: Interferon Alfa-2b, Ribavirin
Interferon:dosage,5 million units/person;frequency,every other day (qod);duration,48 weeks;Subcutaneous injection.
Ribavirin: dosage,15mg/kg/day;frequency,three times a day (t.i.d);duration,48 weeks;take orally.
Hepatitis C virus (HCV) infection rate in China is about 3%, which means about 30 million patients. Combination therapy of ribavirin and interferons (IFN) is the standard clinical treatment of HCV chronical infections. However, overall rate of sustained virological response (SVR) still do not exceed 60% even with ribavirin and peg-IFN. Due to several virus- and patient-related factors, treatment is even less successful in certain populations, especially in HCV genotype 1 infection. Thus the standard therapy duration is optimized according to the virus genotype in the clinical practice. Nowadays, two direct antiviral agents (DAAs) have been approved by Food and Drug Administration (FDA) of USA this year, which increases the SVR rate. However, high price, side effects and long duration render people to hesitate about the addition of the third drug in the traditional prescription.
Predicting the outcome of traditional therapy is the cornerstone of the personalized therapy for HCV infected patients. In order to obtain an accurate prediction, different methods have been tried. Several indicators have been suggested to predict the final treatment outcomes. Rapid Virus Response (RVR), which indicates the non-detectable virus at the forth week since therapy starts, has been used to predict the final treatment outcome.Other indicators, including virus genotype, host genotype of IL-28B, human race and interferon stimulated genes (ISG) expression have also been shown to relate to and be able to predict the treatment outcomes to some extent. Here the investigators propose that the HCV virus dynamics analysis will give a more precise prediction for the therapy outcome.
The general idea is that blood HCV titration data is obtained continuously in the early treatment period (first 6 weeks) of the patients who have strictly followed the therapy method. These titration data will be used to draw virus dynamics curve and calculate the corresponding parameters individually. The parameter(s) that can distinguish patients who reach the therapy evaluation standard from those who failed to reach the evaluation standard will be selected out, and such parameter(s) may be used to predict the therapy outcome of a new patient in the early stage of his/her treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01434212
|First Hospital Jilin University|
|Changchun, Jilin, China, 130061|
|Study Chair:||Junqi Niu, PhD/MD||First Hospital Jilin University|
|Principal Investigator:||Bing Sun, PhD/MD||Chinese Academy of Sciences|