Real World Study About Anti-viral Regimen Adjustment on Achieving Complete Response in CHB Patients (REACH)
4 de agosto de 2021 actualizado por: caidachuan, The Second Affiliated Hospital of Chongqing Medical University
Real World Study on the Effect of HBV-DNA High-precision Detection Based Anti-viral Regimen Adjustment on Achieving Complete Virologic Response in Patients With Chronic Hepatitis B.(REACH)
In the treatment of chronic hepatitis B (CHB), viral suppression is closely related to disease progression, and the lower the viral load, the lower the risk of progression to cirrhosis and hepatocellular carcinoma (HCC).
In addition, a considerable number of patients in China are still using non-first-line antiviral therapy, such as adefovir dipivoxil, lamivudine, and telbivudine (ADV/LAM/LdT).
About 25% of patients who received entecavir(ETV) treatment for more than half a year and confirmed that their DNA had turned negative by non-high-precision detection methods still had low viremia (LLV,DNA>20 IU/ml,IU=international unit), and LLV patients were twice as likely to develop HCC as patients with complete viral response.Patients who have received ETV or second-line NA(LAM/ADV/LdT) treatment for more than half a year to 1 year and confirmed HBV-DNA>10IU/ml by high-precision detection method are recommended to adjust the treatment plan in order to reduce the DNA load below 10IU/ml as soon as possible.
It is up to the doctor, in consultation with the patient, to decide whether or not to make the adjustment.
Descripción general del estudio
Estado
Desconocido
Condiciones
Intervención / Tratamiento
Descripción detallada
In our hospital, about 150 patients are screened for HBV-DNA every day. Therefore, 54 million patients will be tested for HBV-DNA within one year, of which 30% are estimated to be HBV-DNA ≥10 IU. These patients will be informed to the Department of Infectious Diseases of the Second Affiliated Hospital of Chongqing Medical University for follow-up, and will be randomly divided into three groups according to 1:1. Patients in all three groups will be educated about hepatitis B virus infection and antiviral treatment, and the treatment regimen will be adjusted according to whether their HBV DNA is ≥10 IU/ml or not. Patients in group 1: patients with persistant low level HBV DNA (<10 IU/ml). Patients in group 2: HBV-DNA≥10 IU/ml, receiving HBV-related education and being advised by the doctor to change or to add another NA. Patients in group 2: patients with persistant HBV DNA (>10 IU/ml) but refuse to change the regimen. Patients in group 3: patients with persistant HBV DNA (>10 IU/ml) and agree to change the regimen. Educational methods include videos, including an introduction to hepatitis B virus (disease profile, infection, outcome, HBV infection, vertical transmission and other risk factors) for 5 minutes, brochures with relevant information and consultations with physicians and nurses.
All patients with chronic hepatitis B(CHB) receiving ETV or second-line NA(LAM/ADV/LdT) treatment for more than six months to one year will receive HBV-DNA detection, and patients with HBV-DNA≥10 IU/ml will be informed and recommended to adjust the treatment regimen so that the actual prevalence of HBV-DNA load < 10 IU/ml in Chongqing HBV cohort could be obtained . The investigators estimated that 30% of the patients had HBV-DNA≥ 10 IU/ml, so there were about 16,200 patients had HBV-DNA≥ 10 IU/ml among 54,000 patients a year. These patients will be diagnosed with LLV and will undergo a treatment regimen adjustment, with a recommendation to switch to or use a different type of nucleos(t)ide analogue (NA) for anti-viral treatment.
Tipo de estudio
De observación
Inscripción (Anticipado)
10000
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Chongqing
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Chongqing, Chongqing, Porcelana, 400010
- Reclutamiento
- The Second Affiliated Hospital of Chongqing Medical University
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Contacto:
- DACHUAN CAI, PhD
- Número de teléfono: 862362887039
- Correo electrónico: 597521685@qq.com
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Contacto:
- PENG HU, PhD
- Número de teléfono: 8613608338064
- Correo electrónico: hp_cq@163.com
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Investigador principal:
- DACHUAN CAI, Professor
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
14 años a 70 años (Niño, Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Método de muestreo
Muestra no probabilística
Población de estudio
The research subjects were patients with CHB (chronic hepatitis B) receiving ETV or second-line NA(LAM/ADV/LdT) who were admitted to The Second Affiliated Hospital of Chongqing Medical University and other centers.
Descripción
Inclusion Criteria:
- any patients treated with ETV\LAM\ADF\LDT\TDF\TAF.【ADV=adefovir dipivoxil, LAM=lamivudine, and LdT=telbivudine , TAF =Tenofovir alafenamide Fumarate, ETV=Entecavir and TDF=Tenofovir disoproxil fumarate 】
Exclusion Criteria:
- with a expected life span <48 weeks
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
|---|---|
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patients with persistant low level HBV DNA (<10 IU/ml)
No further intervention(s) to be administered except for monitoring of HBV DNA viraemia
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monitoring the viraemia only
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patients with persistant HBV DNA (>10 IU/ml) but refuse to change the regimen
All patients with CHB receiving ETV or second-line NA(LAM/ADV/LdT) treatment for more than six months to one year will receive HBV-DNA detection, and patients with HBV-DNA≥10 IU/ml will be informed and recommended to adjust the treatment regimen.
If those patients refuse to change the regimen which they are using , No further intervention(s) to be administered except for monitoring of HBV DNA viraemia until those patients change their idea
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if those patients agree, the regimen will be changed.
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patients with persistant HBV DNA (>10 IU/ml) and agree to change the regimen
All patients with CHB receiving ETV or second-line NA(LAM/ADV/LdT) treatment for more than six months to one year will receive HBV-DNA detection, and patients with HBV-DNA≥10 IU/ml will be informed and recommended to adjust the treatment regimen.They will change their regimen according one which they are using.
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Based on ongoing one, regimen will be changed .
The principle for adjusting anti-viral regimen is as follows: 1.
The patients were treated with second-line drugs: changing ADV to ETV/TAF/TDF , changing LAM to TAF/TDF and changing LdT to TAF/TDF; 2. The patients were treated with ETV: adding or switching to TAF/TDF;3.
TAF or ETV is recommended for patients with one or more TDF risk factors, such as > 40 years old, patients with abnormal bone/kidney related indicators or patients with high risk of bone/kidney injuries.【ADV=adefovir
dipivoxil, LAM=lamivudine, and LdT=telbivudine , TAF =Tenofovir alafenamide Fumarate, ETV=Entecavir and TDF=Tenofovir disoproxil fumarate 】
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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The proportion of patients who received a complete virologic response (HBV DNA<10IU/ml) at 24 weeks after therapy adjustment.
Periodo de tiempo: 24 weeks
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The proportion of patients who received a complete virologic response (HBV DNA<10IU/ml) at 24 weeks after therapy adjustment.
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24 weeks
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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The proportion of patients with complete virologic response (HBV DNA<10IU/ml) at 12 weeks, 48 weeks and 96 weeks after therapy adjustment.
Periodo de tiempo: 12 weeks, 48 weeks ,96 weeks
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The proportion of patients with complete virologic response (HBV DNA<10IU/ml) at 12 weeks, 48 weeks and 96 weeks after therapy adjustment.
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12 weeks, 48 weeks ,96 weeks
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he proportion of patients with normal Alanine transaminase（ALT） at baseline and at each follow-up time point
Periodo de tiempo: baseline,12 weeks,48 weeks,96 weeks
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he proportion of patients with normal Alanine transaminase（ALT ）at baseline and at each follow-up time point
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baseline,12 weeks,48 weeks,96 weeks
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Changes of estimated glomerularfiltrationratee(GFR) compared with baseline at each follow-up time point.
Periodo de tiempo: baseline,12 weeks,48 weeks,96 weeks
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Changes of estimated glomerularfiltrationratee(GFR) compared with baseline at each follow-up time point.
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baseline,12 weeks,48 weeks,96 weeks
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Changes of serum creatinine(SCr）compared with baseline at each follow-up time point.
Periodo de tiempo: baseline,12 weeks,48 weeks,96 weeks
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Changes of serum creatinine(SCr) compared with baseline at each follow-up time point.
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baseline,12 weeks,48 weeks,96 weeks
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Changes of bone mass density（BMD) compared with baseline at each follow-up time point.
Periodo de tiempo: baseline,12 weeks,48 weeks,96 weeks
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Changes of bone mass density (BMD) compared with baseline at each follow-up time point.
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baseline,12 weeks,48 weeks,96 weeks
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Investigadores
- Investigador principal: DACHUAN CAI, PhD, The Second Affiliated Hospital of Chongqing Medical University
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
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- 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.
- Liu J, Liang W, Jing W, Liu M. Countdown to 2030: eliminating hepatitis B disease, China. Bull World Health Organ. 2019 Mar 1;97(3):230-238. doi: 10.2471/BLT.18.219469. Epub 2019 Jan 28.
- Sun Y, Wu X, Zhou J, Meng T, Wang B, Chen S, Liu H, Wang T, Zhao X, Wu S, Kong Y, Ou X, Wee A, Theise ND, Qiu C, Zhang W, Lu F, Jia J, You H. Persistent Low Level of Hepatitis B Virus Promotes Fibrosis Progression During Therapy. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2582-2591.e6. doi: 10.1016/j.cgh.2020.03.001. Epub 2020 Mar 6.
- Kim JH, Sinn DH, Kang W, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment. Hepatology. 2017 Aug;66(2):335-343. doi: 10.1002/hep.28916. Epub 2016 Dec 24.
- Wang J, Sheng Q, Ding Y, Chen R, Sun X, Chen X, Dou X, Lu F. HBV RNA virion-like particles produced under nucleos(t)ide analogues treatment are mainly replication-deficient. J Hepatol. 2018 Apr;68(4):847-849. doi: 10.1016/j.jhep.2017.10.030. Epub 2017 Nov 4. No abstract available.
- Ogawa E, Nomura H, Nakamuta M, Furusyo N, Koyanagi T, Dohmen K, Ooho A, Satoh T, Kawano A, Kajiwara E, Takahashi K, Azuma K, Kato M, Shimoda S, Hayashi J; Kyushu University Liver Disease Study (KULDS) Group. Tenofovir alafenamide after switching from entecavir or nucleos(t)ide combination therapy for patients with chronic hepatitis B. Liver Int. 2020 Jul;40(7):1578-1589. doi: 10.1111/liv.14482. Epub 2020 Apr 30.
- Cui F, Shen L, Li L, Wang H, Wang F, Bi S, Liu J, Zhang G, Wang F, Zheng H, Sun X, Miao N, Yin Z, Feng Z, Liang X, Wang Y. Prevention of Chronic Hepatitis B after 3 Decades of Escalating Vaccination Policy, China. Emerg Infect Dis. 2017 May;23(5):765-772. doi: 10.3201/eid2305.161477.
- Chen JD, Yang HI, Iloeje UH, You SL, Lu SN, Wang LY, Su J, Sun CA, Liaw YF, Chen CJ; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer in HBV (REVEAL-HBV) Study Group. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology. 2010 May;138(5):1747-54. doi: 10.1053/j.gastro.2010.01.042. Epub 2010 Jan 28.
- Liu C, Wang L, Xie H, Zhang L, Wang B, Luo C, Wang S, Tang M, Fu Z, Ruan H, Liu Z, Wei L, Yi W, Xie Y. The relationship between serum hepatitis B virus DNA level and liver histology in patients with chronic HBV infection. PLoS One. 2018 Nov 7;13(11):e0206060. doi: 10.1371/journal.pone.0206060. eCollection 2018.
- Zhang W, Wang X, Wang Y, Zhao X, Duan W, Wang Q, Wu X, Kong Y, Ma H, You H, Ou X, Jia J. Effective viral suppression is necessary to reduce hepatocellular carcinoma development in cirrhotic patients with chronic hepatitis B: Results of a 10-year follow up. Medicine (Baltimore). 2017 Nov;96(44):e8454. doi: 10.1097/MD.0000000000008454.
- Jang JW, Choi JY, Kim YS, Yoo JJ, Woo HY, Choi SK, Jun CH, Lee CH, Sohn JH, Tak WY, Lee YR, Han KH. Effects of Virologic Response to Treatment on Short- and Long-term Outcomes of Patients With Chronic Hepatitis B Virus Infection and Decompensated Cirrhosis. Clin Gastroenterol Hepatol. 2018 Dec;16(12):1954-1963.e3. doi: 10.1016/j.cgh.2018.04.063. Epub 2018 May 9.
- Dandri M, Petersen J. Mechanism of Hepatitis B Virus Persistence in Hepatocytes and Its Carcinogenic Potential. Clin Infect Dis. 2016 Jun 1;62 Suppl 4(Suppl 4):S281-8. doi: 10.1093/cid/ciw023.
- Kim HJ, Cho YK, Jeon WK, Kim BI. Clinical characteristics of patients with chronic hepatitis B who developed genotypic resistance to entecavir: Real-life experience. Clin Mol Hepatol. 2017 Dec;23(4):323-330. doi: 10.3350/cmh.2017.0005. Epub 2017 Sep 5.
- Sun Y, Zhou J, Wang L, Wu X, Chen Y, Piao H, Lu L, Jiang W, Xu Y, Feng B, Nan Y, Xie W, Chen G, Zheng H, Li H, Ding H, Liu H, Lv F, Shao C, Wang T, Ou X, Wang B, Chen S, Wee A, Theise ND, You H, Jia J. New classification of liver biopsy assessment for fibrosis in chronic hepatitis B patients before and after treatment. Hepatology. 2017 May;65(5):1438-1450. doi: 10.1002/hep.29009. Epub 2017 Mar 22.
- Yenilmez E, Cetinkaya RA, Tural E. Diagnostic Dilemma for Low Viremia with Significant Fibrosis; is Hepatitis B Virus DNA Threshold Level a Good Indicator for Predicting Liver Damage? Balkan Med J. 2018 Jul 24;35(4):326-332. doi: 10.4274/balkanmedj.2017.0888. Epub 2018 May 4.
- Sinn DH, Lee J, Goo J, Kim K, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Yoo BC, Paik SW. Hepatocellular carcinoma risk in chronic hepatitis B virus-infected compensated cirrhosis patients with low viral load. Hepatology. 2015 Sep;62(3):694-701. doi: 10.1002/hep.27889. Epub 2015 Jul 3.
- Papatheodoridis GV, Manolakopoulos S, Touloumi G, Vourli G, Raptopoulou-Gigi M, Vafiadis-Zoumbouli I, Vasiliadis T, Mimidis K, Gogos C, Ketikoglou I, Manesis EK; HEPNET. Greece Cohort Study Group. Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s) starting with lamivudine monotherapy: results of the nationwide HEPNET. Greece cohort study. Gut. 2011 Aug;60(8):1109-16. doi: 10.1136/gut.2010.221846. Epub 2011 Jan 26.
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- Kim TS, Sinn DH, Kang W, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Hepatitis B virus DNA levels and overall survival in hepatitis B-related hepatocellular carcinoma patients with low-level viremia. J Gastroenterol Hepatol. 2019 Nov;34(11):2028-2035. doi: 10.1111/jgh.14750. Epub 2019 Jul 28.
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- Yim HJ, Kim IH, Suh SJ, Jung YK, Kim JH, Seo YS, Yeon JE, Kim CW, Kwon SY, Park SH, Lee MS, Um SH, Byun KS. Switching to tenofovir vs continuing entecavir for hepatitis B virus with partial virologic response to entecavir: a randomized controlled trial. J Viral Hepat. 2018 Nov;25(11):1321-1330. doi: 10.1111/jvh.12934. Epub 2018 Jun 6.
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Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
1 de diciembre de 2020
Finalización primaria (Anticipado)
1 de julio de 2022
Finalización del estudio (Anticipado)
31 de diciembre de 2022
Fechas de registro del estudio
Enviado por primera vez
17 de enero de 2021
Primero enviado que cumplió con los criterios de control de calidad
22 de enero de 2021
Publicado por primera vez (Actual)
26 de enero de 2021
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
5 de agosto de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
4 de agosto de 2021
Última verificación
1 de enero de 2021
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Enfermedades virales
- Infecciones
- Infecciones transmitidas por la sangre
- Enfermedades contagiosas
- Enfermedades del HIGADO
- Hepatitis, Viral, Humana
- Infecciones por Hepadnaviridae
- Infecciones por virus de ADN
- Hepatitis Crónica
- Hepatitis B
- Hepatitis
- Hepatitis B Crónica
Otros números de identificación del estudio
- 2020LCYJ009
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
producto fabricado y exportado desde los EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .