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

HCV Clinical Trial

— RAVs  

Official title:

Safety of Sofosbuvir Plus Daclatasvir in Patients With Chronic Hepatitis c Virus and Assessment of Resistance Associated Variants in Resistant and Relapsed Cases

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03572140
• Other study ID #: RAVS in HCV
• Status: Not yet recruiting
• Start date: July 1, 2018
• Est. completion date: August 1, 2020

Study information

• Verified date: June 2018
• Source: Assiut University
• Contact: Rasha Ali, Assistant lecturer
• Phone: 01062821017
• Email: rasha.maree77[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 297
• Est. completion date: August 1, 2020
• Est. primary completion date: July 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• HCV

Intervention

Diagnostic Test:
• RAVS In relapsed and resistent cases
assessment of RAVS in relapsed and resistant cases after sofosbuvir plus daclatasvir regimen

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (6)

Ben Ari Z. [Chronic hepatitis C infection--eradication of the virus]. Harefuah. 2014 Jul;153(7):392-3, 433. Hebrew. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Reig M, Mariño Z, Perelló C, Iñarrairaegui M, Ribeiro A, Lens S, Díaz 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. — View Citation

Outcome

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