NCT04047680

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

Evolution of Estimated Glomerular Filtration Rate in Chronic Hepatitis C Patients Receiving Sofosbuvir-based or Sofosbuvir-free Direct Acting Antivirals

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 441 (actual)
• Sponsor: National Taiwan University Hospital · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	Sofosbuvir / Velpatasvir Oral Tablet	Sofosbuvir/velpatasvir for 12 weeks
DRUG	Sofosbuvir and Ledipasvir	Sofosbuvir and ledipasvir for 12 weeks
DRUG	Sofosbuvir Tablets	Sofosbuvir plus ribavirin (RBV) or daclatasvir (DCV) for 12 weeks
DRUG	Ombitasvir/paritaprevir/ritonavir	Ombitasvir/paritaprevir/ritonavir for 12 weeks
DRUG	Elbasvir / Grazoprevir Oral Tablet	Elbasvir/grazoprevir for 12 weeks
DRUG	Glecaprevir and Pibrentasvir	Glecaprevir/pibrentasvir for 12 weeks

Timeline

• Start date: 2015-02-01
• Primary completion: 2018-12-01
• Completion: 2019-06-01
• First posted: 2019-08-07
• Last updated: 2019-08-08

Locations

2 sites across 1 country: Taiwan