Hepatitis CNCT04047680
eGFR Evolution in HCV Patients Receiving SOF-based or SOF-free DAAs
An observational study of Hepatitis C and Renal Disease, run by National Taiwan University Hospital at 2 sites in Taiwan.
Trial summary
Data regarding the nephrotoxicity of sofosbuvir (SOF) remain controversial. The investigators compared the changes of estimated glomerular filtration rate (eGFR) in patients with chronic hepatitis C virus (HCV) infection receiving SOF-based or SOF-free direct acting antivirals (DAAs). Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Hepatitis C, Renal Disease, Viral Hepatitis C
- What is being tested?
- Sofosbuvir / Velpatasvir Oral Tablet, Sofosbuvir and Ledipasvir and Sofosbuvir Tablets
- Type of treatment
- Pill or oral medicine
- How many people
- 441 participants
- Where
- 2 sitesTaiwan
- Study dates
- Feb 2015to Jun 2019
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Chronic hepatitis C virus-infected patients with compensated liver diseases and baseline eGFR of 30 mL/min/1.73m2 or more, who received SOF-based or SOF-free DAAs for 12 weeks, and who received off-therapy follow-up until week 24
Who may be able to join
- Chronic HCV patients receiving SOF-based or SOF-free DAAs for 12 weeks
Who cannot join
- Decompensated cirrhosis (Child-Pugh B or C)
- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2
- Active hepatocellular carcinoma (HCC)
- Organ transplantation
- Hepatitis B virus (HBV) co-infection
- Human immunodeficiency virus (HIV) co-infection
- Not received off-therapy follow-up till week 24
Trial locations and contacts
2 sites in 1 country.
Taiwan2 sites
National Taiwan University Hospital, Yun-Lin Branch
Douliu, 10002
National Taiwan University Hospital
Taipei, 10002
About this study
Official title: Evolution of Estimated Glomerular Filtration Rate in Chronic Hepatitis C Patients Receiving Sofosbuvir-based or Sofosbuvir-free Direct Acting Antivirals
Data regarding the nephrotoxicity of sofosbuvir (SOF) remain controversial. The investigators compared the changes of estimated glomerular filtration rate (eGFR) in patients with chronic hepatitis C virus (HCV) infection receiving SOF-based or SOF-free direct acting antivirals (DAAs).
Read the detailed description
Chronic hepatitis C virus (HCV) infection is a major health problem that affects 71 million people worldwide. Patients with chronic HCV infection may present with various hepatic and extrahepatic manifestations which lead to substantial morbidity and mortality. In contrast, the long-term health outcome improves following successful HCV eradication by antiviral therapies.
Owing to the excellent efficacy and safety as well as the short treatment duration, the use of interferon (IFN)-free direct acting antivirals (DAAs) has become the standard-of-care for managing HCV. Sofosbuvir (SOF) is a pyrimidine nucleotide analogue which acts as the HCV ribonucleic acid (RNA) chain terminator by inhibiting HCV non-structural protein 5B (NS5B) RNA-dependent RNA polymerase following intrahepatic activation to uridine triphosphate form. Dephosphorylation results in the formation of inactive metabolite (GS-331007) that undergoes extensive renal excretion. Clinically, SOF is administered once-daily with pangenotypic potency, well tolerability and a high genetic barrier to drug resistance. Furthermore, SOF can be used in combination with NS3/4A protease inhibitors (PIs), NS5A inhibitors, and/or ribavirin (RBV) to achieve high rates of sustained virologic response (SVR). Therefore, applying SOF-based DAAs for HCV is welcome to most treating physicians.
Following the widespread use of SOF-based DAAs for treating HCV in different populations, a large-scale real-world HCV-TARGET study enrolling 1,789 patients indicated that patients with a baseline eGFR ≤ 45 mL/min/1.73m2 were associated with a higher risk of worsening renal function than those with a baseline eGFR > 45 mL/min/1.73m2 following SOF-based DAAs. Moreover, three retrospective studies showed that SOF-based DAAs negatively affected the on-treatment and off-therapy eGFR. On the contrary, other studies showed that the use of SOF-based DAAs did not worsen the eGFR. Because most studies were retrospective in nature without protocol-defined time point for eGFR assessment or patient election, and did not enroll patients receiving SOF-free DAAs as the controls, the investigators thus conducted a prospective study to evaluate the evolution of eGFR in patients with chronic HCV infection receiving SOF-based or SOF-free DAAs.
- Conditions
- Hepatitis C, Renal Disease, Viral Hepatitis C
- Being tested
- Sofosbuvir / Velpatasvir Oral Tablet, Sofosbuvir and Ledipasvir, Sofosbuvir Tablets, Ombitasvir/paritaprevir/ritonavir, Elbasvir / Grazoprevir Oral Tablet
- Keywords
- Viral hepatitis C, Glomerular filtration rate, Direct acting antiviral agent, Sofosbuvir
- Medical subject headings
- Hepatitis C, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sofosbuvir / Velpatasvir Oral TabletDrug
Also called Epclusa
Sofosbuvir/velpatasvir for 12 weeks
Sofosbuvir and LedipasvirDrug
Also called Harvoni
Sofosbuvir and ledipasvir for 12 weeks
Sofosbuvir TabletsDrug
Also called Solvadi
Sofosbuvir plus ribavirin (RBV) or daclatasvir (DCV) for 12 weeks
Ombitasvir/paritaprevir/ritonavirDrug
Also called Viekirax/exviera
Ombitasvir/paritaprevir/ritonavir for 12 weeks
Elbasvir / Grazoprevir Oral TabletDrug
Also called Zepatier
Elbasvir/grazoprevir for 12 weeks
Glecaprevir and PibrentasvirDrug
Also called Maviret
Glecaprevir/pibrentasvir for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| SOF-based DAAs | Patients receiving sofosbuvir (SOF)-based direct acting antiviral agents (DAAs) for 12 weeks Receives: Drug: Sofosbuvir / Velpatasvir Oral Tablet; Drug: Sofosbuvir and Ledipasvir; Drug: Sofosbuvir Tablets | |
| SOF-free DAAs | Patients receiving sofosbuvir (SOF)-free direct acting antiviral agents (DAAs) for 12 weeks Receives: Drug: Ombitasvir/paritaprevir/ritonavir; Drug: Elbasvir / Grazoprevir Oral Tablet; Drug: Glecaprevir and Pibrentasvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Slope differences of eGFR
Slope differences of eGFR between SOF-based and SOF-free DAAs
Measured: Baseline to off-therapy week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2019
- Study startFeb 2015
- Primary completionDec 2018
- Study completionJun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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
- 441 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jia-Horng Kao, PhD, Study director, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04047680
- Sponsor's protocol ID
- 201509009RINB
- Status last verified
- Aug 2019
- First submitted
- 5 Aug 2019
- Last updated
- 8 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Liu CH, Lee MH, Lin JW, Liu CJ, Su TH, Tseng TC, Chen PJ, Chen DS, Kao JH. Evolution of eGFR in chronic HCV patients receiving sofosbuvir-based or sofosbuvir-free direct-acting antivirals. J Hepatol. 2020 May;72(5):839-846. doi: 10.1016/j.jhep.2019.11.014. Epub 2019 Nov 29.
PubMed 31790766
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evolution of Estimated Glomerular Filtration Rate in Chronic Hepatitis C Patients Receiving Sofosbuvir-based or Sofosbuvir-free Direct Acting Antivirals
- ClinicalTrials.gov ID
- NCT04047680
- Acronym / sponsor ID
- 201509009RINB
- Conditions
- Hepatitis C, Renal Disease, Viral Hepatitis C
- Keywords
- Viral hepatitis C, Glomerular filtration rate, Direct acting antiviral agent, Sofosbuvir
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 441 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Feb 2015 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Jun 2019 (actual)
- First posted
- 7 Aug 2019 (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.
Data regarding the nephrotoxicity of sofosbuvir (SOF) remain controversial. The investigators compared the changes of estimated glomerular filtration rate (eGFR) in patients with chronic hepatitis C virus (HCV) infection receiving SOF-based or SOF-free direct acting antivirals (DAAs).
Detailed description
Chronic hepatitis C virus (HCV) infection is a major health problem that affects 71 million people worldwide. Patients with chronic HCV infection may present with various hepatic and extrahepatic manifestations which lead to substantial morbidity and mortality. In contrast, the long-term health outcome improves following successful HCV eradication by antiviral therapies.
Owing to the excellent efficacy and safety as well as the short treatment duration, the use of interferon (IFN)-free direct acting antivirals (DAAs) has become the standard-of-care for managing HCV. Sofosbuvir (SOF) is a pyrimidine nucleotide analogue which acts as the HCV ribonucleic acid (RNA) chain terminator by inhibiting HCV non-structural protein 5B (NS5B) RNA-dependent RNA polymerase following intrahepatic activation to uridine triphosphate form. Dephosphorylation results in the formation of inactive metabolite (GS-331007) that undergoes extensive renal excretion. Clinically, SOF is administered once-daily with pangenotypic potency, well tolerability and a high genetic barrier to drug resistance. Furthermore, SOF can be used in combination with NS3/4A protease inhibitors (PIs), NS5A inhibitors, and/or ribavirin (RBV) to achieve high rates of sustained virologic response (SVR). Therefore, applying SOF-based DAAs for HCV is welcome to most treating physicians.
Following the widespread use of SOF-based DAAs for treating HCV in different populations, a large-scale real-world HCV-TARGET study enrolling 1,789 patients indicated that patients with a baseline eGFR ≤ 45 mL/min/1.73m2 were associated with a higher risk of worsening renal function than those with a baseline eGFR > 45 mL/min/1.73m2 following SOF-based DAAs. Moreover, three retrospective studies showed that SOF-based DAAs negatively affected the on-treatment and off-therapy eGFR. On the contrary, other studies showed that the use of SOF-based DAAs did not worsen the eGFR. Because most studies were retrospective in nature without protocol-defined time point for eGFR assessment or patient election, and did not enroll patients receiving SOF-free DAAs as the controls, the investigators thus conducted a prospective study to evaluate the evolution of eGFR in patients with chronic HCV infection receiving SOF-based or SOF-free DAAs.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SOF-based DAAs | – | Drug: Sofosbuvir / Velpatasvir Oral Tablet, Drug: Sofosbuvir and Ledipasvir, Drug: Sofosbuvir TabletsPatients receiving sofosbuvir (SOF)-based direct acting antiviral agents (DAAs) for 12 weeks |
| SOF-free DAAs | – | Drug: Ombitasvir/paritaprevir/ritonavir, Drug: Elbasvir / Grazoprevir Oral Tablet, Drug: Glecaprevir and PibrentasvirPatients receiving sofosbuvir (SOF)-free direct acting antiviral agents (DAAs) for 12 weeks |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Chronic hepatitis C virus-infected patients with compensated liver diseases and baseline eGFR of 30 mL/min/1.73m2 or more, who received SOF-based or SOF-free DAAs for 12 weeks, and who received off-therapy follow-up until week 24
Key inclusion criteria (1 listed)
- Chronic HCV patients receiving SOF-based or SOF-free DAAs for 12 weeks
Key exclusion criteria (7 listed)
- Decompensated cirrhosis (Child-Pugh B or C)
- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2
- Active hepatocellular carcinoma (HCC)
- Organ transplantation
- Hepatitis B virus (HBV) co-infection
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 |
|---|---|---|
| Sofosbuvir / Velpatasvir Oral TabletAlso: EpclusaSofosbuvir/velpatasvir for 12 weeks | Drug | SOF-based DAAs |
| Sofosbuvir and LedipasvirAlso: HarvoniSofosbuvir and ledipasvir for 12 weeks | Drug | SOF-based DAAs |
| Sofosbuvir TabletsAlso: SolvadiSofosbuvir plus ribavirin (RBV) or daclatasvir (DCV) for 12 weeks | Drug | SOF-based DAAs |
| Ombitasvir/paritaprevir/ritonavirAlso: Viekirax/exvieraOmbitasvir/paritaprevir/ritonavir for 12 weeks | Drug | SOF-free DAAs |
| Elbasvir / Grazoprevir Oral TabletAlso: ZepatierElbasvir/grazoprevir for 12 weeks | Drug | SOF-free DAAs |
| Glecaprevir and PibrentasvirAlso: MaviretGlecaprevir/pibrentasvir for 12 weeks | Drug | SOF-free DAAs |
Primary outcome
Slope differences of eGFR
Time frame: Baseline to off-therapy week 24
Slope differences of eGFR between SOF-based and SOF-free DAAs
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2019.
- Derived from this study: PubMed 31790766Liu CH, Lee MH, Lin JW, Liu CJ, Su TH, Tseng TC, Chen PJ, Chen DS, Kao JH. Evolution of eGFR in chronic HCV patients receiving sofosbuvir-based or sofosbuvir-free direct-acting antivirals. J Hepatol. 2020 May;72(5):839-846. doi: 10.1016/j.jhep.2019.11.014. Epub 2019 Nov 29.
- Individual participant dataSharing planned: No
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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.
Jia-Horng Kao, PhD study director
National Taiwan University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis C and Renal Disease, run by National Taiwan University Hospital at 2 sites in Taiwan.
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 7 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: finished, as of the sponsor's last update on 8 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Slope differences of eGFR (time frame: Baseline to off-therapy week 24). 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 NCT04047680, which also lists 1 linked publication.
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 8 Aug 2019.