- ICH GCP
- Registr klinických studií v USA
- Klinická studie 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)
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Očekávaný)
Kontakty a umístění
Studijní místa
-
-
Jilin
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Changchun, Jilin, Čína, 130061
- Nábor
- First Hospital Jilin University
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Kontakt:
- Yu Pan, PhD/MD
- Telefonní číslo: 0431-88782120
- E-mail: panyu20000@yahoo.com.cn
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Kontakt:
- Xiumei Chi, PhD/MD
- Telefonní číslo: 0431-88782222
- E-mail: xiumeichi@hotmail.com
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Vrchní vyšetřovatel:
- Yu Pan, PhD/MD
-
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dítě
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Metoda odběru vzorků
Studijní populace
Popis
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:
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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
Studijní plán
Jak je studie koncipována?
Detaily designu
Kohorty a intervence
Skupina / kohorta |
Intervence / Léčba |
|---|---|
|
Interferon a ribavirin
Všichni pacienti dodržovali standardní léčebný protokol.
|
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.
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Absolute Blood HCV RNA Copies at designed time points
Časové okno: 0hr,24hr,1wk,2wk,4wk,6wk,12wk,24wk,48wk,72wk
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Blood HCV RNA copies were assayed with Roche - COBAS® AmpliPrep/COBAS® TaqMan® HCV Test.
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0hr,24hr,1wk,2wk,4wk,6wk,12wk,24wk,48wk,72wk
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
HCV genotyp
Časové okno: Základní linie
|
HCV NS5A je klonován do T vektoru a sekvenován pro evoluční analýzu.
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Základní linie
|
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Historie zneužívání drog
Časové okno: Základní linie
|
Pacienti budou dotázáni na jejich historii užívání drog.
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Základní linie
|
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Polymorfismus IL-28B
Časové okno: Základní linie
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Polymorfismus genu IL28,rs8099917,rs12979860 atd.
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Základní linie
|
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Alanine Aminotransferase (ALT) and Aspartate transaminase (AST)
Časové okno: Baseline,4wk,12wk,24wk,48wk
|
ALT AST are assayed to detect the hepatic function.
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Baseline,4wk,12wk,24wk,48wk
|
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Fibrosis stage
Časové okno: Baseline,4wk,12wk,24wk,48wk
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Fibrosis is analyzed with Fibroscan.
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Baseline,4wk,12wk,24wk,48wk
|
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Regular blood test
Časové okno: Baseline,4wk,12wk,24wk,48wk
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The distribution and absolute count of the different types of blood cells are assayed.
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Baseline,4wk,12wk,24wk,48wk
|
|
Electrocardiography
Časové okno: Baseline,4wk,12wk,24wk,48wk
|
Electrocardiography is taken to avoid severe side effects.
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Baseline,4wk,12wk,24wk,48wk
|
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Alcohol ,smoking condition
Časové okno: Baseline,4wk,12wk,24wk,48wk
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Patients are asked whether they take alcohol or smoke cigarettes during the therapy period.
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Baseline,4wk,12wk,24wk,48wk
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Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Studijní židle: Bing Sun, Doctor, Chinese Academy of Sciences
- Ředitel studie: Chen Yang, Doctor, Chinese Academy of Sciences
Publikace a užitečné odkazy
Obecné publikace
- 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Očekávaný)
Dokončení studie (Očekávaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Odhad)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Nemoci trávicího systému
- RNA virové infekce
- Virová onemocnění
- Infekce
- Infekce přenášené krví
- Přenosné nemoci
- Infekce Flaviviridae
- Hepatitida, virová, lidská
- Enterovirové infekce
- Infekce Picornaviridae
- Hepatitida, chronická
- Onemocnění jater
- Hepatitida
- Žloutenka typu A
- Hepatitida C
- Hepatitida C, chronická
- Fyziologické účinky léků
- Molekulární mechanismy farmakologického působení
- Antiinfekční látky
- Antivirová činidla
- Antimetabolity
- Antineoplastická činidla
- Imunologické faktory
- Interferony
- Interferon-alfa
- Ribavirin
- Interferon alfa-2
Další identifikační čísla studie
- 2012ZX10002007
- 2009ZX10004-105-jida02 (Jiné číslo grantu/financování: Ministry of Science and Technology)
- 2008ZX10002-014-jida02 (Jiné číslo grantu/financování: Ministry of Science and Technology)
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