Patterns of Early Hepatitis C Virus Decline Predict the Outcome of Interferon Therapy

NCT ID: NCT01434212

Last Updated: 2011-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-05-31

Study Completion Date

2011-12-31

Brief Summary

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The purpose of this study is to determine whether the outcome of interferon therapy on HCV infected patients can be early precisely predicted with a novel mathematic method with Chinese population.

Detailed Description

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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.

Conditions

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Hepatitis

Keywords

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HCV dynamics Mathematical model Interferon Predict Hepatitis C Virus

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Interferon and ribavirin

All the patients followed the standard treatment protocol.

Interferon Alfa-2b, Ribavirin

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Generic: Recombinant Human Interferon alpha-2b,Ribavirin Brand: Kaiyinyisheng,Weilake FDA Approval number:S20030032,H10940157

Eligibility Criteria

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Inclusion Criteria

* Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
* Serum HCV-RNA \> 3 log IU/ml
* Has been infected by HCV for more than 6 months
* ALT,AST have been elevated continuously, inflammation and necrosis have been observed according to the histology diagnosis (G\>=2),modest liver fibrosis (S\>=2)
* For those patients whose ALT are normal,treatment accord to the liver biopsy. If obvious fibrosis has been detected (S2,S3),treatment should be done.For those S0,S1 stage patients, treatment could be delayed, but ALT/AST should be assayed every 3-6 months.
* Compensated liver disease
* Patients have never been treated with traditional interferon plus ribavirin or peginterferon plus ribavirin

Exclusion Criteria

History:

* Has history of decompensated liver diseases
* Has been treated with other anti-virus drugs,or anti-tumor drugs,immuno-suppression drugs
* Has a history of autoimmune hepatitis
* History of a severe seizure disorder or current anticonvulsant use
* History or other evidence of a medical condition associated with chronic liver disease other than HCV which would make the patient, in the opinion of the investigator, unsuitable for the study (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
* Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4g/dL (as may be seen with ribavirin therapy) would not be well-tolerated
* History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease

Current condition:

* Pregnant women or women during the lactation period
* Co-infected with hepatitis b virus or human immunodeficiency virus
* Liver cancer or alpha-fetoprotein \> 100ng/ml
* Blood neutrophils count \< 1500/mm3, or platelets count \< 90000/mm3
* Female hemoglobin \<11.5g/dL, male hemoglobin \<12.5g/dL
* Blood creatinine \> 1.5 ULN
* Have severe mental diseases,especially depression
* Severe pulmonary dysfunction
* Severe cardiovascular disease
* Uncontrolled diabetes
* Uncontrolled thalassemia
* Evidence of alcohol abuse (alcohol consumption\>40 g/day)
* Unwillingness to provide informed consent or abide by the requirements of the study
* Local or System malignancy unstable status
Minimum Eligible Age

20 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chinese Academy of Sciences

OTHER_GOV

Sponsor Role collaborator

The First Hospital of Jilin University

OTHER

Sponsor Role lead

Responsible Party

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Junqi Niu

Vice-President of First Hospital of Jilin University

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Junqi Niu, PhD/MD

Role: STUDY_CHAIR

First Hospital Jilin University

Bing Sun, PhD/MD

Role: PRINCIPAL_INVESTIGATOR

Chinese Academy of Sciences

Locations

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First Hospital Jilin University

Changchun, Jilin, China

Site Status

Countries

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China

References

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Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, Perelson AS. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science. 1998 Oct 2;282(5386):103-7. doi: 10.1126/science.282.5386.103.

Reference Type BACKGROUND
PMID: 9756471 (View on PubMed)

Dahari H, Ribeiro RM, Perelson AS. Triphasic decline of hepatitis C virus RNA during antiviral therapy. Hepatology. 2007 Jul;46(1):16-21. doi: 10.1002/hep.21657.

Reference Type BACKGROUND
PMID: 17596864 (View on PubMed)

Snoeck E, Chanu P, Lavielle M, Jacqmin P, Jonsson EN, Jorga K, Goggin T, Grippo J, Jumbe NL, Frey N. A comprehensive hepatitis C viral kinetic model explaining cure. Clin Pharmacol Ther. 2010 Jun;87(6):706-13. doi: 10.1038/clpt.2010.35. Epub 2010 May 12.

Reference Type BACKGROUND
PMID: 20463660 (View on PubMed)

Dixit NM, Layden-Almer JE, Layden TJ, Perelson AS. Modelling how ribavirin improves interferon response rates in hepatitis C virus infection. Nature. 2004 Dec 16;432(7019):922-4. doi: 10.1038/nature03153.

Reference Type BACKGROUND
PMID: 15602565 (View on PubMed)

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65. doi: 10.1016/s0140-6736(01)06102-5.

Reference Type BACKGROUND
PMID: 11583749 (View on PubMed)

Dill MT, Duong FH, Vogt JE, Bibert S, Bochud PY, Terracciano L, Papassotiropoulos A, Roth V, Heim MH. Interferon-induced gene expression is a stronger predictor of treatment response than IL28B genotype in patients with hepatitis C. Gastroenterology. 2011 Mar;140(3):1021-31. doi: 10.1053/j.gastro.2010.11.039. Epub 2010 Nov 25.

Reference Type BACKGROUND
PMID: 21111740 (View on PubMed)

Araujo ES, Dahari H, Neumann AU, de Paula Cavalheiro N, Melo CE, de Melo ES, Layden TJ, Cotler SJ, Barone AA. Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients. J Viral Hepat. 2011 Apr;18(4):e52-60. doi: 10.1111/j.1365-2893.2010.01358.x.

Reference Type BACKGROUND
PMID: 20738775 (View on PubMed)

Related Links

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Other Identifiers

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2008ZX10002-014-jida01

Identifier Type: OTHER

Identifier Source: secondary_id

2009ZX10004-105-jida01

Identifier Type: OTHER

Identifier Source: secondary_id

2008ZX10004-002-jida01

Identifier Type: -

Identifier Source: org_study_id