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Trial record 77 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

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

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ClinicalTrials.gov Identifier: NCT04047680
Recruitment Status : Completed
First Posted : August 7, 2019
Last Update Posted : August 8, 2019
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

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).

Condition or disease Intervention/treatment
Hepatitis C Renal Disease Viral Hepatitis C Drug: Sofosbuvir / Velpatasvir Oral Tablet Drug: Sofosbuvir and Ledipasvir Drug: Sofosbuvir Tablets Drug: Ombitasvir/paritaprevir/ritonavir Drug: Elbasvir / Grazoprevir Oral Tablet Drug: Glecaprevir and Pibrentasvir

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.


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Study Type : Observational
Actual Enrollment : 441 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Evolution of Estimated Glomerular Filtration Rate in Chronic Hepatitis C Patients Receiving Sofosbuvir-based or Sofosbuvir-free Direct Acting Antivirals
Actual Study Start Date : February 2015
Actual Primary Completion Date : December 2018
Actual Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir

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 Name: Epclusa

Drug: Sofosbuvir and Ledipasvir
Sofosbuvir and ledipasvir for 12 weeks
Other Name: Harvoni

Drug: Sofosbuvir Tablets
Sofosbuvir plus ribavirin (RBV) or daclatasvir (DCV) for 12 weeks
Other Name: 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 Name: Viekirax/exviera

Drug: Elbasvir / Grazoprevir Oral Tablet
Elbasvir/grazoprevir for 12 weeks
Other Name: Zepatier

Drug: Glecaprevir and Pibrentasvir
Glecaprevir/pibrentasvir for 12 weeks
Other Name: Maviret




Primary Outcome Measures :
  1. Slope differences of eGFR [ Time Frame: Baseline to off-therapy week 24 ]
    Slope differences of eGFR between SOF-based and SOF-free DAAs



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04047680


Locations
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Taiwan
National Taiwan University Hospital, Yun-Lin Branch
Douliu, Taiwan, 10002
National Taiwan University Hospital
Taipei, Taiwan, 10002
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
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Study Director: Jia-Horng Kao, PhD National Taiwan University Hospital

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Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT04047680     History of Changes
Other Study ID Numbers: 201509009RINB
First Posted: August 7, 2019    Key Record Dates
Last Update Posted: August 8, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Taiwan University Hospital:
Viral hepatitis C
Glomerular filtration rate
Direct acting antiviral agent
Sofosbuvir
Additional relevant MeSH terms:
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MK-5172
Hepatitis A
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ritonavir
Sofosbuvir
Ledipasvir
Velpatasvir
Ledipasvir, sofosbuvir drug combination
Antiviral Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors