drugset / Trial / NCT03753074
Effectiveness of TAF in Reducing Clinical Events in CHB Patients Beyond Treatment Indications by Current Guidelines
Phase 4
Active not recruiting
780 enrolled
Young-Suk Lim
Chang Gung Memorial Hospital · collabChi Mei Medical Hospital · collabChiayi Christian Hospital · collabChina Medical University Hospital · collabChung-Ang University Hospital · collabDalin Tzu Chi General Hospital · collabE-DA Hospital · collabKaohsiung Medical University · collabKonkuk University Medical Center · collabKorea University Guro Hospital · collabKyunghee University Medical Center · collabKyungpook National University Hospital · collabNational Cheng-Kung University Hospital · collabSamsung Medical Center · collabSeoul National University Bundang Hospital · collabSeoul National University Hospital · collabSeoul St. Mary's Hospital · collabSt. Martin De Porress Hospital · collabTaichung Veterans General Hospital · collabTaitung Mackay Memorial Hospital · collabUlsan University Hospital · collab
RandomizedParallel-groupOpen-labelTreatment
Summary
Treatment with Tenofovir Alafenamide(TAF) in Chronic Hepatitis B (CHB) patients classified as beyond treatment indication of current international guidelines (e.g. aged more than 40 years old and 4 ≤ log HBV-DNA IU/mL \< 8) is expected to bring improvement in long-term clinical outcomes. This expected result may expand the treatment indications in patients with CHB based on age and HBV-DNA in contrast to current international guidelines of CHB.
Timeline
- Start
- 2019-02-18
- Primary completion
- 2031-12-31
- Completion
- 2031-12-31
Outcome
Met primary endpoint
paper the primary endpoint occurred in 11 participants: two in the tenofovir alafenamide group (both hepatocellular carcinoma) and nine in the observation group PMID 39914435 ↗
paper hazard ratio 0·21 [97·5% CI 0·04-1·20]; p=0·027 PMID 39914435 ↗
Publications
- Background Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.
- Background European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.
- Background Tseng TC, Kao JH. Treating Immune-tolerant Hepatitis B. J Viral Hepat. 2015 Feb;22(2):77-84. doi: 10.1111/jvh.12370. Epub 2014 Nov 25.
- Background Andreani T, Serfaty L, Mohand D, Dernaika S, Wendum D, Chazouilleres O, Poupon R. Chronic hepatitis B virus carriers in the immunotolerant phase of infection: histologic findings and outcome. Clin Gastroenterol Hepatol. 2007 May;5(5):636-41. doi: 10.1016/j.cgh.2007.01.005. Epub 2007 Apr 11.
- Background Hui CK, Leung N, Yuen ST, Zhang HY, Leung KW, Lu L, Cheung SK, Wong WM, Lau GK; Hong Kong Liver Fibrosis Study Group. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase. Hepatology. 2007 Aug;46(2):395-401. doi: 10.1002/hep.21724.
- Background Kennedy PTF, Sandalova E, Jo J, Gill U, Ushiro-Lumb I, Tan AT, Naik S, Foster GR, Bertoletti A. Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B. Gastroenterology. 2012 Sep;143(3):637-645. doi: 10.1053/j.gastro.2012.06.009. Epub 2012 Jun 15.
- Background Lai M, Hyatt BJ, Nasser I, Curry M, Afdhal NH. The clinical significance of persistently normal ALT in chronic hepatitis B infection. J Hepatol. 2007 Dec;47(6):760-7. doi: 10.1016/j.jhep.2007.07.022. Epub 2007 Sep 24.
- Background 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.
- Background Kim GA, Lim YS, Han S, Choi J, Shim JH, Kim KM, Lee HC, Lee YS. High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B. Gut. 2018 May;67(5):945-952. doi: 10.1136/gutjnl-2017-314904. Epub 2017 Oct 21.
- Background 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.
- Background Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006 Mar;130(3):678-86. doi: 10.1053/j.gastro.2005.11.016.
- Background Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, Sun Y, Xuan SY. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011 Mar;53(3):726-36. doi: 10.1002/hep.24105. Epub 2011 Feb 11.
- Background Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, S Sulkowski M, Torriani FJ, Dieterich DT, Thomas DL, Messinger D, Nelson M; APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006 Jun;43(6):1317-25. doi: 10.1002/hep.21178.
- Lim YS, Yu ML, Choi J, Chen CY, Choi WM, Kang W, Kim GA, Kim HJ, Lee YB, Lee JH, Park NH, Kwon SY, Park SY, Kim JH, Choi GH, Jang ES, Chen CH, Hsu YC, Bair MJ, Cheng PN, Tung HD, Chang TS, Lo CC, Tseng KC, Yang SS, Peng CY, Han S. Early antiviral treatment with tenofovir alafenamide to prevent serious clinical adverse events in adults with chronic hepatitis B and moderate or high viraemia (ATTENTION): interim results from a randomised controlled trial. Lancet Gastroenterol Hepatol. 2025 Apr;10(4):295-305. doi: 10.1016/S2468-1253(24)00431-X. Epub 2025 Feb 3.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | tenofovir alafenamide | Small molecule | 25 mg | Oral |