Antiviral Therapy for Patients With Chronic Hepatitis B Infection
Exploratory Study on Antiviral Therapy for Patients With Chronic Hepatitis B Virus Infection (Immune Tolerance Period)
The study aims to demonstrate that antiviral therapy for patients with immune tolerance of CHB. On the basis of the original antiviral therapy of entecavir, further clarify the safety and effectiveness of entecavir combined with tenofovir amibufenamide.The investigators plan to enroll about 328 hepatitis B patients,. who are in the stage of immune tolerance. These participants will be devided into two groups randomly .Group A will receive the treatment of entecavir. Group B will be treated with entecavir and tenofovir amibufenamide. The participants in both groups will be followed up for 96 weeks.
The primary endpoint is to compare the inhibition rate of HBV-DNA between two groups. The secondary endpoint includes: (1) Comparing the decrease of HBV DNA at 48 weeks between the two groups. (2) Comparing the HBeAg seroconversion rates at 48 weeks and 96 weeks between the two groups. (3) The changes of HBsAg at 48 weeks and 96 weeks between the two groups. (4) Comparing adverse side effects between the two groups.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
High HBV DNA level is an independent risk factor for liver cirrhosis and liver cancer, we know all patients with chronic hepatitis B virus infection in immune tolerance period had high viral load. So it is necessary to implement antiviral therapy for patients with chronic hepatitis B virus infection in immune tolerance period.Previous studies have found that combination of two antiviral drugs has a higher virological inhibition rate in patients with high viral load than single drug. Hence, the investigators' hypothesis is that treatment of patients with chronic hepatitis B virus infection in immune tolerance period result in higher virological inhibition rate and reduce of the risk of cirrhosis and liver cancer.
The investigators plan to enroll about 328 hepatitis B patients, who are in the stage of immune tolerance. These participants will be devided into 2 groups.Group A will receive the treatment of entecavir . Group B will be treated with entecavir and tenofovir amibufenamide. The participants in both groups will be followed up for 96 weeks. Unless there are serious adverse drug reactions, the protocol cannot be adjusted within 96 weeks.
The primary endpoint is to compare the inhibition rate of HBV-DNA between two groups. The secondary endpoint includes: (1) Comparing the decrease of HBV DNA at 48 weeks between the two groups. (2) Comparing the HBeAg seroconversion rates at 48 weeks and 96 weeks between the two groups. (3) The changes of HBsAg at 48 weeks and 96 weeks between the two groups. (4) Comparing adverse side effects between the two groups.
Undersøgelsestype
Tilmelding (Forventet)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Guangdong
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Guangzhou, Guangdong, Kina, 510630
- Rekruttering
- The third affiliated hospital of Sun Yat-Sen University
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Kontakt:
- Bingliang Lin, Doctor
- Telefonnummer: 86-20-85253165
- E-mail: lamikin@126.com
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Kontakt:
- jing Xiong, Master
- Telefonnummer: 86-20-85253165
- E-mail: 373599983@qq.com
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Age between 18-65 years old;
- HBsAg positive >6 months, HBsAg>1*10e4IU/ml;
- HBV-DNA> 2 * 10e7IU / ml;
- HBeAg positive;
- ALT / AST remained normal which were followed up twice within 1 year with at least a 6-month interval each time.
- No antiviral treatment with interferon or nucleoside (acid) analogues in the previous year
Exclusion Criteria:
- infection with hepatitis A, C, D, E viruses or HIV infection ;
- Combined with diabetes, hypertension, renal insufficiency, autoimmune diseases and other organ dysfunction And malignant tumors;
- Patients using Immunosuppressive therapy or radiotherapy / chemotherapy for other diseases;
- Patients with liver fibrosis, cirrhosis (FibroScan > = 9.4kpa) and liver cancer were identified;
- Extrahepatic manifestations related to HBV (glomerulonephritis, vasculitis, nodular polyarteritis, peripheral neuropathy, etc.);
- Allergic to nucleoside drugs
- Pregnancy or having pregnancy plan within 2 years and Lactating patients;
- Patients who are unable to comply with the arrange ment of this study or sign the informed consent.
- Failed to return to hospital regularly for follow-up ac- cording to the study plan.
- Researchers determine other condition that does not fit into the study.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Enkelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: Entecavir group
Patients receive treatment with entecavir
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Entecavir group will receive entecavir orally once a day, 0.5mg each time, and fasting for 2h before and after taking the medicine
Andre navne:
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Eksperimentel: Entecavir and Tenofovir Amibufenamide group
Patients will receive the treatment of entecavir combined with tenofovir amibufenamide
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Entecavir combined with Tenofovir Amibufenamide group will be treated with entecavir and tenofovir amibufenamide.
Entecavir is administered in the same way as before.
enofovir amibufenamide orally 25mg once a day with meals
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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The inhibition rate of HBV-DNA between two groups
Tidsramme: 96 weeks
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compare the inhibition rate of HBV-DNA between two groups at 96 weeks
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96 weeks
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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The decrease of HBV DNA in the at 48 weeks between the two groups
Tidsramme: 48 weeks
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comparing the decrease of HBV DNA in the at 48 weeks between the two groups
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48 weeks
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The HBeAg seroconversion rates at 48 weeks and 96 weeks
Tidsramme: 48 weeks and 96 weeks
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comparing the HBeAg seroconversion rates at 48 weeks and 96 weeks between the two groups
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48 weeks and 96 weeks
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The changes of HBsAg
Tidsramme: 48 weeks and 96 weeks
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The changes of HBsAg at 48 weeks and 96 weeks were compared between the two groups
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48 weeks and 96 weeks
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adverse side effects
Tidsramme: 4、12、24、48、72 and 96 weeks
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comparing adverse side effects between the two groups
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4、12、24、48、72 and 96 weeks
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Samarbejdspartnere og efterforskere
Sponsor
Publikationer og nyttige links
Generelle publikationer
- Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65.
- Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007 Feb;45(2):507-39. doi: 10.1002/hep.21513. No abstract available. Erratum In: Hepatology. 2007 Jun;45(6):1347.
- Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008 Feb;48(2):335-52. doi: 10.1016/j.jhep.2007.11.011. Epub 2007 Dec 4.
- Lok AS, McMahon BJ, Brown RS Jr, Wong JB, Ahmed AT, Farah W, Almasri J, Alahdab F, Benkhadra K, Mouchli MA, Singh S, Mohamed EA, Abu Dabrh AM, Prokop LJ, Wang Z, Murad MH, Mohammed K. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology. 2016 Jan;63(1):284-306. doi: 10.1002/hep.28280. Epub 2015 Nov 13.
- Kumar M, Sarin SK, Hissar S, Pande C, Sakhuja P, Sharma BC, Chauhan R, Bose S. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology. 2008 May;134(5):1376-84. doi: 10.1053/j.gastro.2008.02.075. Epub 2008 Feb 29.
- Wong GL, Chan HL, Mak CW, Lee SK, Ip ZM, Lam AT, Iu HW, Leung JM, Lai JW, Lo AO, Chan HY, Wong VW. Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients with liver cirrhosis. Hepatology. 2013 Nov;58(5):1537-47. doi: 10.1002/hep.26301. Epub 2013 Sep 30.
- Wong GL, Wong VW, Chan HY, Tse PC, Wong J, Chim AM, Yiu KK, Chu SH, Chan HL. Undetectable HBV DNA at month 12 of entecavir treatment predicts maintained viral suppression and HBeAg-seroconversion in chronic hepatitis B patients at 3 years. Aliment Pharmacol Ther. 2012 Jun;35(11):1326-35. doi: 10.1111/j.1365-2036.2012.05098.x. Epub 2012 Apr 16.
- Zoutendijk R, Reijnders JG, Zoulim F, Brown A, Mutimer DJ, Deterding K, Hofmann WP, Petersen J, Fasano M, Buti M, Berg T, Hansen BE, Sonneveld MJ, Wedemeyer H, Janssen HL; VIRGIL Surveillance Study Group. Virological response to entecavir is associated with a better clinical outcome in chronic hepatitis B patients with cirrhosis. Gut. 2013 May;62(5):760-5. doi: 10.1136/gutjnl-2012-302024. Epub 2012 Apr 5.
- Tang LSY, Covert E, Wilson E, Kottilil S. Chronic Hepatitis B Infection: A Review. JAMA. 2018 May 1;319(17):1802-1813. doi: 10.1001/jama.2018.3795. Erratum In: JAMA. 2018 Sep 18;320(11):1202.
- Raffetti E, Fattovich G, Donato F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: a systematic review and meta-analysis. Liver Int. 2016 Sep;36(9):1239-51. doi: 10.1111/liv.13142. Epub 2016 May 22.
- Chayanupatkul M, Omino R, Mittal S, Kramer JR, Richardson P, Thrift AP, El-Serag HB, Kanwal F. Hepatocellular carcinoma in the absence of cirrhosis in patients with chronic hepatitis B virus infection. J Hepatol. 2017 Feb;66(2):355-362. doi: 10.1016/j.jhep.2016.09.013. Epub 2016 Sep 28.
- Wong GL, Chan HL, Chan HY, Tse PC, Tse YK, Mak CW, Lee SK, Ip ZM, Lam AT, Iu HW, Leung JM, Wong VW. Accuracy of risk scores for patients with chronic hepatitis B receiving entecavir treatment. Gastroenterology. 2013 May;144(5):933-44. doi: 10.1053/j.gastro.2013.02.002. Epub 2013 Feb 12.
- Wong GL, Wong VW, Choi PC, Chan AW, Chim AM, Yiu KK, Chan HY, Chan FK, Sung JJ, Chan HL. Clinical factors associated with liver stiffness in hepatitis B e antigen-positive chronic hepatitis B patients. Clin Gastroenterol Hepatol. 2009 Feb;7(2):227-33. doi: 10.1016/j.cgh.2008.10.023. Epub 2008 Oct 30.
- Seto WK, Lai CL, Ip PP, Fung J, Wong DK, Yuen JC, Hung IF, Yuen MF. A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B. PLoS One. 2012;7(2):e32622. doi: 10.1371/journal.pone.0032622. Epub 2012 Feb 28.
- Lok AS, Trinh H, Carosi G, Akarca US, Gadano A, Habersetzer F, Sievert W, Wong D, Lovegren M, Cohen D, Llamoso C. Efficacy of entecavir with or without tenofovir disoproxil fumarate for nucleos(t)ide-naive patients with chronic hepatitis B. Gastroenterology. 2012 Sep;143(3):619-628.e1. doi: 10.1053/j.gastro.2012.05.037. Epub 2012 May 27.
- Chan HL, Chan CK, Hui AJ, Chan S, Poordad F, Chang TT, Mathurin P, Flaherty JF, Lin L, Corsa A, Gaggar A, Subramanian GM, McHutchison JG, Lau G, Lee S, Gane EJ. Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA. Gastroenterology. 2014 May;146(5):1240-8. doi: 10.1053/j.gastro.2014.01.044. Epub 2014 Jan 23. Erratum In: Gastroenterology. 2015 Jan;148(1):263. Lau, George [added].
- Mauss S, Berger F, Filmann N, Hueppe D, Henke J, Hegener P, Athmann C, Schmutz G, Herrmann E. Effect of HBV polymerase inhibitors on renal function in patients with chronic hepatitis B. J Hepatol. 2011 Dec;55(6):1235-40. doi: 10.1016/j.jhep.2011.03.030. Epub 2011 May 19.
- Duarte-Rojo A, Heathcote EJ. Efficacy and safety of tenofovir disoproxil fumarate in patients with chronic hepatitis B. Therap Adv Gastroenterol. 2010 Mar;3(2):107-19. doi: 10.1177/1756283X09354562.
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Forventet)
Studieafslutning (Forventet)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Sygdomme i fordøjelsessystemet
- Patologiske processer
- RNA-virusinfektioner
- Blodbårne infektioner
- Sygdomsegenskaber
- Leversygdomme
- Hepatitis, viral, menneskelig
- Hepadnaviridae infektioner
- DNA-virusinfektioner
- Enterovirus infektioner
- Picornaviridae infektioner
- Infektioner
- Overførbare sygdomme
- Hepatitis B
- Hepatitis
- Hepatitis A
- Virussygdomme
- Hepatitis B, kronisk
- Hepatitis, kronisk
- Herpesviridae infektioner
- Molekylære mekanismer for farmakologisk virkning
- Anti-infektionsmidler
- Antivirale midler
- Reverse transkriptasehæmmere
- Nukleinsyresyntesehæmmere
- Enzymhæmmere
- Anti-HIV-midler
- Anti-retrovirale midler
- Tenofovir
- Entecavir
Andre undersøgelses-id-numre
- Treatment for CHB infection
Plan for individuelle deltagerdata (IPD)
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