A Study for G1b CHC Patients With CKD-3 Treated With Grazoprevir Plus Elbasvir

Chronic Kidney Disease stage3 Clinical Trial

Official title:

A Prospective Multicenter Observational Study for Characterization of Renal Function G1b CHC Patients With CKD-3 Treated With Grazoprevir Plus Elbasvir

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03144635
• Other study ID #: KULDS-001
• Status: Completed
• Phase: Phase 4
• Start date: April 1, 2017
• Est. completion date: September 20, 2018

Study information

• Verified date: February 2019
• Source: Kyushu University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The regimen using grazoprevir plus elbasvir treatment is promising in Japan, because it may safely be used for the elderly patients with renal dysfunction. Grazoprevir and elbasvir are metabolized in the liver and do not require dose-adjustment for patients with renal dysfunction. However, no data related to efficacy and safety of the grazoprevir plus elbasvir treatment for Japanese elderly patients with renal dysfunction (eGFR<60 mL/min/1.73m2) have been reported. Therefore, physicians are at a loss whether or not to treat the patients with renal dysfunction due to no evidence.

The aim of this study is to investigate the improvement of serum endostatin level of Japanese patients with CKD stage 3 after grazoprevir (NS3/4A protease inhibitor) plus elbasvir (NS5A replication complex inhibitor) treatment by a prospective, multicenter cohort study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: September 20, 2018
• Est. primary completion date: December 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

1. Subjects aged 20 years or older.

2. Patients positive for HCV RNA for over 6 months and infected with genotype 1b chronic hepatitis C, including compensated cirrhosis.

3. Patients without co-infection of hepatitis B virus.

4. Patients without co-infection of human immunodeficiency virus

5. Patients with moderate chronic kidney disease (CKD stage 3) (eGFR: 30-59 mL/min/1.73m2). A diagnosis of CKD is only confirmed if repeated eGFR tests for at least 90 days.

Exclusion Criteria:

1. Patients with decompensated cirrhosis (Child Pugh B and C)

2. Patients with albumin <3.0 g/dL and platelets <75,000 /µL

3. Patients with autoimmune hepatitis

4. Constant heavy alcohol drinkers (converted to ethanol =60 g/day)

5. Patients who have a history of hypersensitivity to grazoprevir and elbasvir

6. Patients who are pregnant females, or females who may become pregnant, or females who are breastfeeding

7. Patients with heart disease that is hard to control (e.g., very recent cardiac infarction, severe heart failure, unstable arrhythmia)

8. Patients who are under medication with drugs listed as contraindication in a package insert of grazoprevir plus elbasvir treatment

9. Patients judged (by the physician in charge of research) to be inappropriate as subjects for the study for any other reasons.

Related Conditions & MeSH terms

• Chronic Kidney Disease stage3
• Hepatitis C
• Hepatitis C Viral
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Grazoprevir plus Elbasvir
An oral dose of 100 mg/day of grazoprevir as well as an oral dose of 50 mg/day of elbasvir for 12 weeks.

Locations

Country	Name	City	State
Japan	Kyushu University Hospital	Fukuoka

Sponsors (2)

Lead Sponsor	Collaborator
Kyushu University	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Japan, 

References & Publications (3)

Furusyo N, Ogawa E, Nakamuta M, Kajiwara E, Nomura H, Dohmen K, Takahashi K, Satoh T, Azuma K, Kawano A, Tanabe Y, Kotoh K, Shimoda S, Hayashi J; Kyushu University Liver Disease Study (KULDS) Group. Telaprevir can be successfully and safely used to treat older patients with genotype 1b chronic hepatitis C. J Hepatol. 2013 Aug;59(2):205-12. doi: 10.1016/j.jhep.2013.03.020. Epub 2013 Mar 28. — View Citation

Ogawa E, Furusyo N, Kajiwara E, Nomura H, Kawano A, Takahashi K, Dohmen K, Satoh T, Azuma K, Nakamuta M, Koyanagi T, Kotoh K, Shimoda S, Hayashi J. Comparative effectiveness and safety study of triple therapy with simeprevir or telaprevir for non-cirrhotic patients with chronic hepatitis C virus genotype 1b infection. J Gastroenterol Hepatol. 2015 Dec;30(12):1759-67. doi: 10.1111/jgh.13016. — View Citation

Ogawa E, Furusyo N, Yamashita N, Kawano A, Takahashi K, Dohmen K, Nakamuta M, Satoh T, Nomura H, Azuma K, Koyanagi T, Kotoh K, Shimoda S, Kajiwara E, Hayashi J; Kyushu University Liver Disease Study(KULDS) Group. Effectiveness and safety of daclatasvir plus asunaprevir for patients with hepatitis C virus genotype 1b aged 75 years and over with or without cirrhosis. Hepatol Res. 2017 Mar;47(3):E120-E131. doi: 10.1111/hepr.12738. Epub 2016 Jun 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of Serum Endostatin Level (ng/mL) From Baseline to 3 Months	We evaluated the serum endostatin at baseline and 3 months after the treatment initiation.	3 months
Primary	Change of eGFR Level (mL/Min/1.73m^2) From Baseline to 3 Months	We evaluated eGFR level at baseline and 3 months after the treatment initiation.	3 months
Secondary	Sustained Virological Response-12 (SVR12)	SVR12 was defined as undetectable HCV RNA at week 12 after the end of treatment.	3 months
Secondary	Change of Serum Alanine Aminotransferase (ALT) Level (U/L) From Baseline to 3 Months	We evaluated the serum ALT levels at baseline and 3 months after the treatment initiation.	3 months
Secondary	Change of Serum Alpha-fetoprotein Level (ng/mL) From Baseline to 3 Months	We evaluated the serum alpha-fetoprotein levels at baseline and 3 months after the treatment initiation.	3 months
Secondary	Count of Participants With NS3/4A or NS5A Muttations Who Achieved SVR12	We identified the NS3/4A or NS5A muttations by direct sequencing at baseline. Among participants who had mutations, we calcualted the rate of SVR12.	3 months