Safety of Sofosbuvir ,Daclatasvir in HCV Patients and RAVS in Resistent and Relapsed Cases (RAVs)
Safety of Sofosbuvir Plus Daclatasvir in Patients With Chronic Hepatitis c Virus and Assessment of Resistance Associated Variants in Resistant and Relapsed Cases
To identify side effects of Sofosbuvir/ Daclatasvir treatment regimen of chronic HCV GT-4 infection.
- To assess the occurrence and the prevalence of RAVs in patients with treatment failure and relapse after sofosbuvir and daclatasvir with assessment of their types .
- To examine the GT4 subtypes by phylogenetic analysis and baseline sequence variability among subtypes and their potential impact on treatment outcome and development of viral resistance in patients who received a regimen of Sofosbuvir/ Daclatasvir for treatment of chronic HCV GT-4.
- To assess the differences in patient demographics across GT4 subtypes.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Hepatitis C virus (HCV) chronically infects approximately 120-130 million individuals worldwide .Mortality related to HCV infection has been estimated at approximately 300,000 deaths per year..
Direct antiviral agents (DAAs) effectively eradicate HCV and rapidly improve residual liver functions. Current HCV eradication rates have exceeded 90% in a very short time .
Hepatitis C virus genotype 4 (GT4) is genetically diverse, with 17 confirmed subtypes, and comprises approximately 13% of infections worldwide [3]. In Egypt, GT4 accounts for approximately 90% of infections, with subtype 4a predominating .
Sofosbuvir and daclatasvir are generally well tolerated with only a few adverse effects reported.
Hepatitis C virus resistant associated variants (RAVs) are seen in most patients who do not achieve sustained virological response (SVR). These resistance-associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes.
Donaldson et al performed an analysis on four phase III clinical trials in search of common RAVs against sofosbuvir, discovering L159F, C316N, and V321A were associated with virological failure. Interestingly, this study also verified S282R mutation as associating with failure.
NS5A RAVs can be very common, with Y93H detected in up to 15% of the population and L31M in up to 6.3%. Other RAVs tend to also be fairly common detected in approximately 0.3%-3.5% of the population
Tipo de estudio
Inscripción (Anticipado)
Contactos y Ubicaciones
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Descripción
Inclusion Criteria:
- Anti HCV positive patients either chronic HCV or liver cirrhosis. • Detectable HCV RNA by quantitative polymerase chain reaction (PCR) prior to treatment
Exclusion Criteria:
- Co-infection with hepatitis B virus .
- Presence of malignancy before treatment.
- End-stage liver disease (Child score more than 9).
- Major co-morbid disease e.g heart failure
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
|---|---|
|
group A
RAVS IN resistent cases after daclatasvir plus sofosbuvir treatment
|
assessment of RAVS in relapsed and resistant cases after sofosbuvir plus daclatasvir regimen
|
|
group B
RAVS IN relapsed cases after daclatasvir plus sofosbuvir treatment
|
assessment of RAVS in relapsed and resistant cases after sofosbuvir plus daclatasvir regimen
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
relevance of HC RAVs to the outcomes of therapy with Sofosbuvir in treatment of egyptian patients infected with HCV genotype 4
Periodo de tiempo: baseline
|
that may be used in the future to predict the response to Sofosbuvir and this will save a huge cost for Egypt .
|
baseline
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Ahlam Farghaly, Professor, Assiut University
- Investigador principal: haidi ramadan, Lecturer, Assiut University
Publicaciones y enlaces útiles
Publicaciones Generales
- Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P, Foschi FG, Lenzi M, Mazzella G, Verucchi G, Andreone P, Brillanti S. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016 Oct;65(4):727-733. doi: 10.1016/j.jhep.2016.06.015. Epub 2016 Jun 24.
- Ben Ari Z. [Chronic hepatitis C infection--eradication of the virus]. Harefuah. 2014 Jul;153(7):392-3, 433. Hebrew.
- Reig M, Marino Z, Perello C, Inarrairaegui M, Ribeiro A, Lens S, Diaz A, Vilana R, Darnell A, Varela M, Sangro B, Calleja JL, Forns X, Bruix J. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016 Oct;65(4):719-726. doi: 10.1016/j.jhep.2016.04.008. Epub 2016 Apr 13.
- Kamal SM, Nasser IA. Hepatitis C genotype 4: What we know and what we don't yet know. Hepatology. 2008 Apr;47(4):1371-83. doi: 10.1002/hep.22127.
- Di Lello FA, Neukam K, Parra-Sanchez M, Plaza Z, Soriano V, Cifuentes C, Mira JA, Poveda E, Pineda JA. Hepatitis C virus genotype 4 in Southern and Central Spain does not originate from recent foreign migration waves. J Med Virol. 2013 Oct;85(10):1734-40. doi: 10.1002/jmv.23657. Epub 2013 Jul 16.
- Donaldson EF, Harrington PR, O'Rear JJ, Naeger LK. Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir. Hepatology. 2015 Jan;61(1):56-65. doi: 10.1002/hep.27375. Epub 2014 Nov 20.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Anticipado)
Finalización primaria (Anticipado)
Finalización del estudio (Anticipado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- RAVS in HCV
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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. .