eGFR Evolution in HCV Patients Receiving SOF-based or SOF-free DAAs

August 6, 2019 updated by: National Taiwan University Hospital

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

441

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Douliu, Taiwan, 10002
        • National Taiwan University Hospital, Yun-Lin Branch
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

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

Description

Inclusion Criteria:

  • Chronic HCV patients receiving SOF-based or SOF-free DAAs for 12 weeks

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
SOF-based DAAs
Patients receiving sofosbuvir (SOF)-based direct acting antiviral agents (DAAs) for 12 weeks
Drug: Sofosbuvir / Velpatasvir Oral Tablet
Sofosbuvir/velpatasvir for 12 weeks
Other Names:
  • Epclusa
Drug: Sofosbuvir and Ledipasvir
Sofosbuvir and ledipasvir for 12 weeks
Other Names:
  • Harvoni
Drug: Sofosbuvir Tablets
Sofosbuvir plus ribavirin (RBV) or daclatasvir (DCV) for 12 weeks
Other Names:
  • Solvadi
SOF-free DAAs
Patients receiving sofosbuvir (SOF)-free direct acting antiviral agents (DAAs) for 12 weeks
Drug: Ombitasvir/paritaprevir/ritonavir
Ombitasvir/paritaprevir/ritonavir for 12 weeks
Other Names:
  • Viekirax/exviera
Drug: Elbasvir / Grazoprevir Oral Tablet
Elbasvir/grazoprevir for 12 weeks
Other Names:
  • Zepatier
Drug: Glecaprevir and Pibrentasvir
Glecaprevir/pibrentasvir for 12 weeks
Other Names:
  • Maviret

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Slope differences of eGFR
Time Frame: Baseline to off-therapy week 24
Slope differences of eGFR between SOF-based and SOF-free DAAs
Baseline to off-therapy week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Investigators

  • Study Director: Jia-Horng Kao, PhD, National Taiwan University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 1, 2015

Primary Completion (ACTUAL)

December 1, 2018

Study Completion (ACTUAL)

June 1, 2019

Study Registration Dates

First Submitted

August 5, 2019

First Submitted That Met QC Criteria

August 5, 2019

First Posted (ACTUAL)

August 7, 2019

Study Record Updates

Last Update Posted (ACTUAL)

August 8, 2019

Last Update Submitted That Met QC Criteria

August 6, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201509009RINB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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