TeSLAComparison of Telbivudine Plus Adefovir With Lamivudine Plus Adefovir for the Treatment of Lamivudine-resistant Chronic Hepatitis B at 52 Weeks: A Pilot Study
telbivudine plus adefovir
+ lamivudine plus adefovir
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Estudio de Tratamiento
Resumen
Fecha de inicio: 1 de mayo de 2011
Fecha en la que se inscribió al primer participante.Lamivudine had been widely used for treatment-naïve chronic hepatitis B patients. However, development of antiviral resistance has been known as the major drawback: Incidence of lamivudine resistance was reported to be approximately 70% after 5 years (Lok AS et al, 2003). For the treatment of lamivudine resistance, adefovir has been widely used (Lok AS and McMahon B, 2009). However, switching to adefovir monotherapy was also reported to be at high risk of resistance, 25% at year 2 (Yeon JE et al, 2006). Recently, adding adefovir on lamivudine was shown to be superior to switching to adefovir monotherapy by decreasing the adefovir resistance (Rapti I et al, 2007, Lampertico P et al, 2007). However, combination of adefovir and lamivudine does not increase antiviral activity compared with adefovir monotherapy in patients with lamivudine resistance (Peters MG et al, 2004). As many patients are still viremic with the treatment of lamivudine and adefovir over 1 year, the investigators need more potent combination of the drugs. Telbivudine is a new nucleoside analogue with potent antiviral activity. The previous phase III study has shown the superiority of telbivudine over lamivudine in HBeAg positive and negative subjects (Lai CL et al, 2007). Therefore, telbivudine plus adefovir may be a better treatment option than lamivudine plus adefovir for the lamivudine-resistant chronic hepatitis B patients. No study assessing the efficacy of telbivudine plus adefovir has been conducted for these patients. The aim of this study is to evaluate the safety and efficacy of telbivudine plus adefovir compared with lamivudine plus adefovir in lamivudine resistant chronic hepatitis B patients at the end of 1 year follow-up,
Protocolo
Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.Se reclutarán 60 pacientes
Número total de participantes que el ensayo clínico espera reclutar.Estudio de Tratamiento
Elegibilidad
Los investigadores buscan pacientes que cumplan ciertos criterios, conocidos como criterios de elegibilidad: estado general de salud o tratamientos previos.Cualquier sexo
Sexo biológico de los participantes elegibles para inscribirse.De 18 a 70 años
Rango de edades de los participantes que pueden unirse al estudio.Voluntarios sanos no permitidos
Indica si personas sanas, sin la condición que se estudia, pueden participar.Condiciones
Patología
Criterios
Inclusion Criteria: HBeAg positive or negative chronic hepatitis B patients (positive HBsAg more than 6 months) Age ≥ 18 years old, and ≤70 years old Previous treatment with lamivudine more than 6 months Being on lamivudine at the time of screening Confirmed genotypic resistance to lamivudine by RFMP (rtM204V or I) Presence of virologic breakthrough ≥1 log increase of HBV DNA above na dir) HBV DNA ≥ 20,000 IU/mL Patient willing to give an informed consent (If patient is <20 years old, the parent or legal guardian also need to give an informed consent) Exclusion Criteria: Out of inclusion criteria Presence of adefovir resistance (rtA181T or V, rtN236T) by RFMP assay Laboratory abnormalities as follows at screening: AFP>100 ng/mL, serum phosphorous level<2.4 mg/dL, serum creatinine level> 1.5 mg/dL or creatinine clearance < 50 mL/min Patient with a history of decompensated liver disease: Any patients with a history of ascites, hepatic encephalopathy, variceal bleeding, jaundice, or CTP>7 points should be excluded. History of treatment with nucleos(t)ide analogues other than lamivudine more than 4 weeks History of immune modulatory drugs (interferon, thymosin-alfa) within 24 weeks of screening Liver transplant patient Patient co-infected with HIV, HCV, or HDV Patient with metabolic or genetic liver disease that may affect serum ALT level Habitual alcohol consumption (>140 g/week for male, >70 g/week for female) Patient not able to stop drugs that may affect ALT or HBV DNA level during study periods (ie. Steroid, immune-suppressants, non-steroidal anti-inflammatory drugs, acetaminophen,) Pregnant or lactating woman Menstruating woman unwilling to use appropriate methods of contraception (ie. Condom, oral contraceptives, tubal ligation) Patient with hepatocellular carcinoma (treated or not treated) Patient with any untreated malignancy Patient with history of malignancy cured within 5 years of screening
Plan de Estudio
Conoce todos los tratamientos administrados en este estudio, su descripción detallada y en qué consisten.2 grupos de intervención están designados en este estudio
0% de probabilidad de ser asignado al grupo placebo
Grupos de Tratamiento
Grupo I
Comparador ActivoGrupo II
Comparador ActivoObjetivos del Estudio
Objetivos Primarios
Objetivos Secundarios
Centros del Estudio
Estos son los hospitales, clínicas o centros de investigación donde se lleva a cabo el estudio. Puedes encontrar la ubicación más cercana a ti y su estado de reclutamiento.Este estudio tiene una ubicación
Korea University Ansan Hospital
Ansan, South KoreaAbrir Korea University Ansan Hospital en Google Maps