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

Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04047680
• Other study ID #: 201509009RINB
• Status: Completed
• Start date: February 2015
• Est. completion date: June 2019

Study information

• Verified date: August 2019
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 441
• Est. completion date: June 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Renal Disease
• Viral Hepatitis C

Intervention

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

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital, Yun-Lin Branch	Douliu
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Slope differences of eGFR	Slope differences of eGFR between SOF-based and SOF-free DAAs	Baseline to off-therapy week 24