- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01760148
Patterns of Early Hepatitis C Virus Decline Predict the Outcome of Interferon Therapy (sIFN-pred2) (sIFN-pred2)
Study of Parameters of Early Hepatitis C Virus Dynamics for Predicting the Outcome of Standard Interferon Therapy With Chinese Cohort (Second Phase)
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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 2 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.
Type d'étude
Inscription (Anticipé)
Contacts et emplacements
Lieux d'étude
-
-
Jilin
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Changchun, Jilin, Chine, 130061
- Recrutement
- First Hospital Jilin University
-
Contact:
- Yu Pan, PhD/MD
- Numéro de téléphone: 0431-88782120
- E-mail: panyu20000@yahoo.com.cn
-
Contact:
- Xiumei Chi, PhD/MD
- Numéro de téléphone: 0431-88782222
- E-mail: xiumeichi@hotmail.com
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Chercheur principal:
- Yu Pan, PhD/MD
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Enfant
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Sexes éligibles pour l'étude
Méthode d'échantillonnage
Population étudiée
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
Intervention / Traitement |
|---|---|
|
Interféron et ribavirine
Tous les patients ont suivi le protocole de traitement standard.
|
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.
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Absolute Blood HCV RNA Copies at designed time points
Délai: 0hr,24hr,1wk,2wk,4wk,6wk,12wk,24wk,48wk,72wk
|
Blood HCV RNA copies were assayed with Roche - COBAS® AmpliPrep/COBAS® TaqMan® HCV Test.
|
0hr,24hr,1wk,2wk,4wk,6wk,12wk,24wk,48wk,72wk
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Génotype du VHC
Délai: Ligne de base
|
Le VHC NS5A est cloné dans le vecteur T et séquencé pour une analyse évolutive.
|
Ligne de base
|
|
Antécédents de toxicomanie
Délai: Ligne de base
|
Les patients seront interrogés sur leurs antécédents de consommation de médicaments.
|
Ligne de base
|
|
Polymorphisme IL-28B
Délai: Ligne de base
|
Polymorphisme du gène IL28, rs8099917, rs12979860, etc.
|
Ligne de base
|
|
Alanine Aminotransferase (ALT) and Aspartate transaminase (AST)
Délai: Baseline,4wk,12wk,24wk,48wk
|
ALT AST are assayed to detect the hepatic function.
|
Baseline,4wk,12wk,24wk,48wk
|
|
Fibrosis stage
Délai: Baseline,4wk,12wk,24wk,48wk
|
Fibrosis is analyzed with Fibroscan.
|
Baseline,4wk,12wk,24wk,48wk
|
|
Regular blood test
Délai: Baseline,4wk,12wk,24wk,48wk
|
The distribution and absolute count of the different types of blood cells are assayed.
|
Baseline,4wk,12wk,24wk,48wk
|
|
Electrocardiography
Délai: Baseline,4wk,12wk,24wk,48wk
|
Electrocardiography is taken to avoid severe side effects.
|
Baseline,4wk,12wk,24wk,48wk
|
|
Alcohol ,smoking condition
Délai: Baseline,4wk,12wk,24wk,48wk
|
Patients are asked whether they take alcohol or smoke cigarettes during the therapy period.
|
Baseline,4wk,12wk,24wk,48wk
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chaise d'étude: Bing Sun, Doctor, Chinese Academy of Sciences
- Directeur d'études: Chen Yang, Doctor, Chinese Academy of Sciences
Publications et liens utiles
Publications générales
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Anticipé)
Achèvement de l'étude (Anticipé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système digestif
- Infections par virus à ARN
- Maladies virales
- Infections
- Infections transmissibles par le sang
- Maladies transmissibles
- Infections à Flaviviridae
- Hépatite, virale, humaine
- Infections à entérovirus
- Infections à Picornaviridae
- Hépatite chronique
- Maladies du foie
- Hépatite
- Hépatite A
- Hépatite C
- Hépatite C chronique
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Antimétabolites
- Agents antinéoplasiques
- Facteurs immunologiques
- Interférons
- Interféron-alpha
- Ribavirine
- Interféron alpha-2
Autres numéros d'identification d'étude
- 2012ZX10002007
- 2009ZX10004-105-jida02 (Autre subvention/numéro de financement: Ministry of Science and Technology)
- 2008ZX10002-014-jida02 (Autre subvention/numéro de financement: Ministry of Science and Technology)
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