Tenofovir Alafenamide Versus Entecavir for the Treatment of Chronic Hepatitis B

Официальное название

Tenofovir Alafenamide Versus Entecavir for the Treatment of Chronic Hepatitis B: An Open Label, Randomized Controlled Trial

Обзор

To compare the efficacy and renal safety of tenofovir alafenamide (TAF) versus entecavir (ETV) in the chronic hepatitis B patients.

Подробное описание

With high antiviral potency and low drug resistance rate, both ETV and tenofovir disoproxil fumarate (TDF) have been recommended as the first-line antiviral therapy for chronic hepatitis B (CHB). However, risk of renal dysfunction remains an issue in TDF long-term therapy. Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir and is formulated to deliver the active metabolite to target cells more efficiently than TDF at lower doses, thereby reducing systemic exposure to tenofovir. Importantly, TAF had improved renal safety as compared to TDF. TAF has been approved for treating CHB since 2017; however, it is still unknown whether the efficacy and renal safety of TAF is compatible to those of ETV. The investigators aim to conduct an open label, randomized controlled trial comparing TAF with ETV for assessing their efficacy and renal safety in CHB patients. The eligible CHB patients are randomly assigned (1:1) to receive TAF or ETV. After allocation to TAF group or ETV group, study subjects will receive therapy for 3 years (144 weeks).

Вмешательства

• Препарат Tenofovir alafenamide
  Tenofovir alafenamide 25mg/tab once daily
• Препарат Entecavir
  Entecavir 0.5mg/tab once daily

Первичные конечные точки

• HBV viral suppression [Срок оценки: After 48-week therapy of Tenofovir alafenamide or entecavir]
• Renal safety: Change of estimated glomerular filtration rate [Срок оценки: After 48-week therapy of Tenofovir alafenamide or entecavir]

Вторичные конечные точки (5)

• Renal safety: Change of estimated glomerular filtration rate [Срок оценки: After 144-week therapy of Tenofovir alafenamide or entecavir]
• HBV viral suppression [Срок оценки: After 144-week therapy of Tenofovir alafenamide or entecavir]
• Normalization alanine aminotransferase (ALT) [Срок оценки: After 144-week therapy of Tenofovir alafenamide or entecavir]
• HBsAg loss [Срок оценки: After 144-week therapy of Tenofovir alafenamide or entecavir]
• Bone mineral density [Срок оценки: After 144-week therapy of Tenofovir alafenamide or entecavir]

Критерии участия

Критерии включения

• Patients more than 20 years old
• Chronic hepatitis B patients
• Patients who were indicated for hepatitis B virus antiviral therapy

Критерии исключения

• Decompensated liver disease (Child-Pugh B \&C)
• End stage renal disease (eGRF < 15 ml/min/1.73m2)
• Prior use of nucleot(s)ide analogues for chronic hepatitis B
• Prior use of interferon for chronic hepatitis B within six months
• Known history of human immunodeficiency virus or hepatitis C virus co-infection
• Concurrent other uncontrolled malignancy
• Women in pregnancy or lactation
• Cannot conform to the study protocol of this study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Тайвань · 1 центр

• Taichung Veterans General Hospital — Taichung

Публикации

• Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006 Oct;45(4):529-38. doi: 10.1016/j.jhep.2006.05.013. Epub 2006 Jun 23. PMID 16879891
• Chen DS, Sung JL. Hepatitis B virus infection on Taiwan. N Engl J Med. 1977 Sep 22;297(12):668-9. doi: 10.1056/NEJM197709222971213. No abstract available. PMID 757978
• Ni YH, Chang MH, Wu JF, Hsu HY, Chen HL, Chen DS. Minimization of hepatitis B infection by a 25-year universal vaccination program. J Hepatol. 2012 Oct;57(4):730-5. doi: 10.1016/j.jhep.2012.05.021. Epub 2012 Jun 2. PMID 22668640
• Chiang CJ, Yang YW, Chen JD, You SL, Yang HI, Lee MH, Lai MS, Chen CJ. Significant reduction in end-stage liver diseases burden through the national viral hepatitis therapy program in Taiwan. Hepatology. 2015 Apr;61(4):1154-62. doi: 10.1002/hep.27630. Epub 2015 Feb 10. PMID 25476749
• 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. PMID 29405329
• 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. PMID 28427875
• Kang L, Pan J, Wu J, Hu J, Sun Q, Tang J. Anti-HBV Drugs: Progress, Unmet Needs, and New Hope. Viruses. 2015 Sep 15;7(9):4960-77. doi: 10.3390/v7092854. PMID 26389937
• Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, DeHertogh D, Wilber R, Zink RC, Cross A, Colonno R, Fernandes L; BEHoLD AI463027 Study Group. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2006 Mar 9;354(10):1011-20. doi: 10.1056/NEJMoa051287. PMID 16525138

Идентификаторы

NCT: NCT03933384 · CF18341A · 106DHA0500150

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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