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

NCT ID: NCT04047680

Last Updated: 2019-08-08

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 441 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2019-06-30

Brief 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).

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

SOF-based DAAs

Patients receiving sofosbuvir (SOF)-based direct acting antiviral agents (DAAs) for 12 weeks

Sofosbuvir / Velpatasvir Oral Tablet

Intervention Type: DRUG

Sofosbuvir/velpatasvir for 12 weeks

Sofosbuvir and Ledipasvir

Intervention Type: DRUG

Sofosbuvir and ledipasvir for 12 weeks

Sofosbuvir Tablets

Intervention Type: DRUG

Sofosbuvir plus ribavirin (RBV) or daclatasvir (DCV) for 12 weeks

SOF-free DAAs

Patients receiving sofosbuvir (SOF)-free direct acting antiviral agents (DAAs) for 12 weeks

Ombitasvir/paritaprevir/ritonavir

Intervention Type: DRUG

Ombitasvir/paritaprevir/ritonavir for 12 weeks

Elbasvir / Grazoprevir Oral Tablet

Intervention Type: DRUG

Elbasvir/grazoprevir for 12 weeks

Glecaprevir and Pibrentasvir

Intervention Type: DRUG

Glecaprevir/pibrentasvir for 12 weeks

Interventions

Sofosbuvir / Velpatasvir Oral Tablet

Sofosbuvir/velpatasvir for 12 weeks

Intervention Type: DRUG

Sofosbuvir and Ledipasvir

Sofosbuvir and ledipasvir for 12 weeks

Intervention Type: DRUG

Sofosbuvir Tablets

Sofosbuvir plus ribavirin (RBV) or daclatasvir (DCV) for 12 weeks

Intervention Type: DRUG

Ombitasvir/paritaprevir/ritonavir

Ombitasvir/paritaprevir/ritonavir for 12 weeks

Intervention Type: DRUG

Elbasvir / Grazoprevir Oral Tablet

Elbasvir/grazoprevir for 12 weeks

Intervention Type: DRUG

Glecaprevir and Pibrentasvir

Glecaprevir/pibrentasvir for 12 weeks

Intervention Type: DRUG

Other Intervention Names

Epclusa; Harvoni; Solvadi; Viekirax/exviera; Zepatier; Maviret

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jia-Horng Kao, PhD

Role: STUDY_DIRECTOR

National Taiwan University Hospital

Locations

National Taiwan University Hospital, Yun-Lin Branch

Douliu, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Countries

Taiwan

References

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.

Reference Type: DERIVED

PMID: 31790766 (View on PubMed)

Other Identifiers

201509009RINB

Identifier Type: -

Identifier Source: org_study_id