HCVRAVsNCT03572140
Safety of Sofosbuvir ,Daclatasvir in HCV Patients and RAVS in Resistent and Relapsed Cases
An observational study of HCV, run by Assiut University.
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 . Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- HCV
- What is being tested?
- RAVS In relapsed and resistent cases
- How many people
- 297 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2018to 1 Aug 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Cases will be recruited from the viral hepatitis clinic, department of tropical medicine, Alrajhi Liver hospital, Assiut University. The lab. work will be done by researchers from Medical Microbiology and Immunology department, Faculty of Medicine, Assiut University-University of Cincinnat, USA and Clinical pathology department, Assiut University.
Who may be able to join
- Anti HCV positive patients either chronic HCV or liver cirrhosis. • Detectable HCV RNA by quantitative polymerase chain reaction (PCR) prior to treatment
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
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
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.
Read the 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
- Conditions
- HCV
- Being tested
- RAVS In relapsed and resistent cases
- Keywords
- HCV, Sofosbuvir, Safety, RAVs, Daclatasvir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAVS In relapsed and resistent casesDiagnostic test
assessment of RAVS in relapsed and resistant cases after sofosbuvir plus daclatasvir regimen
| Study group | Role | What they receive |
|---|---|---|
| group A | RAVS IN resistent cases after daclatasvir plus sofosbuvir treatment Receives: Diagnostic Test: RAVS In relapsed and resistent cases | |
| group B | RAVS IN relapsed cases after daclatasvir plus sofosbuvir treatment Receives: Diagnostic Test: RAVS In relapsed and resistent cases |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 .
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2018
- Study start1 Jul 2018 (estimated)
- Primary completion1 Jul 2020 (estimated)
- Study completion1 Aug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HCVStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 297 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rasha Maree Omar Ali, Assiut University
- Investigators
- Ahlam Farghaly, Professor, Principal investigator, Assiut Universityhaidi ramadan, Lecturer, Principal investigator, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03572140
- Sponsor's protocol ID
- RAVS in HCV
- Acronym
- RAVs
- Status last verified
- Jun 2018
- First submitted
- 19 Jun 2018
- Last updated
- 29 Jun 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ben Ari Z. [Chronic hepatitis C infection--eradication of the virus]. Harefuah. 2014 Jul;153(7):392-3, 433. Hebrew.
PubMed 25189028Conti 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.
PubMed 27349488Reig 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.
PubMed 27084592Kamal 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.
PubMed 18240152Di 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.
PubMed 23861220Donaldson 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.
PubMed 25123381
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03572140
- Acronym / sponsor ID
- RAVs / RAVS in HCV
- Conditions
- HCV
- Keywords
- HCV, Sofosbuvir, Safety, RAVs, Daclatasvir
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 297 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Jul 2018 (estimated)
- Primary completion
- 1 Jul 2020 (estimated)
- Study completion
- 1 Aug 2020 (estimated)
- First posted
- 28 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| group A | – | Diagnostic Test: RAVS In relapsed and resistent casesRAVS IN resistent cases after daclatasvir plus sofosbuvir treatment |
| group B | – | Diagnostic Test: RAVS In relapsed and resistent casesRAVS IN relapsed cases after daclatasvir plus sofosbuvir treatment |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Cases will be recruited from the viral hepatitis clinic, department of tropical medicine, Alrajhi Liver hospital, Assiut University. The lab. work will be done by researchers from Medical Microbiology and Immunology department, Faculty of Medicine, Assiut University-University of Cincinnat, USA and Clinical pathology department, Assiut University.
Key inclusion criteria (1 listed)
- Anti HCV positive patients either chronic HCV or liver cirrhosis. • Detectable HCV RNA by quantitative polymerase chain reaction (PCR) prior to treatment
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RAVS In relapsed and resistent casesassessment of RAVS in relapsed and resistant cases after sofosbuvir plus daclatasvir regimen | Diagnostic test | group A, group B |
Primary outcome
relevance of HC RAVs to the outcomes of therapy with Sofosbuvir in treatment of egyptian patients infected with HCV genotype 4
Time frame: baseline
that may be used in the future to predict the response to Sofosbuvir and this will save a huge cost for Egypt .
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2018.
- Background: PubMed 25189028Ben Ari Z. [Chronic hepatitis C infection--eradication of the virus]. Harefuah. 2014 Jul;153(7):392-3, 433. Hebrew.
- Background: PubMed 27349488Conti 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.
- Background: PubMed 27084592Reig 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.
- Background: PubMed 18240152Kamal 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.
- Background: PubMed 23861220Di 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.
- Background: PubMed 25123381Donaldson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahlam Farghaly, Professor principal investigator
Assiut University
haidi ramadan, Lecturer principal investigator
Assiut University
Questions about this trial
What is this clinical trial studying?
An observational study of HCV, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rasha Ali, Assistant lecturer (01062821017, rasha.maree77@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
relevance of HC RAVs to the outcomes of therapy with Sofosbuvir in treatment of egyptian patients infected with HCV genotype 4 (time frame: baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03572140, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2018.