Safety of Sofosbuvir ,Daclatasvir in HCV Patients and RAVS in Resistent and Relapsed Cases

• Conditions: HCV
• Interventions: Diagnostic Test: RAVS In relapsed and resistent cases

• Registration Number: NCT03572140
• Lead Sponsor: Assiut University

Brief Summary

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.

Detailed Description

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

Study Timeline

• Status Verified: 2018-06
• Study First Submitted: 2018-06-19
• Study First Submitted QC: 2018-06-26
• Last Update Submitted: 2018-06-27
• Study First Posted: 2018-06-28
• Last Update Posted: 2018-06-29
• Study Start: 2018-07-01
• Primary Completion: 2020-07-01
• Study Completion: 2020-08-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 297

Inclusion Criteria

• Anti HCV positive patients either chronic HCV or liver cirrhosis. • Detectable HCV RNA by quantitative polymerase chain reaction (PCR) prior to treatment

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
group B	RAVS In relapsed and resistent cases	RAVS IN relapsed cases after daclatasvir plus sofosbuvir treatment
group A	RAVS In relapsed and resistent cases	RAVS IN resistent cases after daclatasvir plus sofosbuvir treatment

Primary Outcome Measures

Name	Time	Method
relevance of HC RAVs to the outcomes of therapy with Sofosbuvir in treatment of egyptian patients infected with HCV genotype 4	baseline	that may be used in the future to predict the response to Sofosbuvir and this will save a huge cost for Egypt .