Clinical trial NCT03144635: A Study for G1b CHC Patients With CKD-3 Treated With Grazoprevir Plus Elbasvir
Official title: A Prospective Multicenter Observational Study for Characterization of Renal Function G1b CHC Patients With CKD-3 Treated With Grazoprevir Plus Elbasvir
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C Viral
Chronic Kidney Disease stage3
Keywords: Direct Acting Antivirals
Grazoprevir
Elbasvir
Lead sponsor: Kyushu University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-05-09
Enrollment: 80
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change of Serum Endostatin Level (ng/mL) From Baseline to 3 Months
timeFrame: 3 months
measure: Change of eGFR Level (mL/Min/1.73m^2) From Baseline to 3 Months
timeFrame: 3 months
Secondary outcomes:
measure: Sustained Virological Response-12 (SVR12)
timeFrame: 3 months
measure: Change of Serum Alanine Aminotransferase (ALT) Level (U/L) From Baseline to 3 Months
timeFrame: 3 months
measure: Change of Serum Alpha-fetoprotein Level (ng/mL) From Baseline to 3 Months
timeFrame: 3 months
measure: Count of Participants With NS3/4A or NS5A Muttations Who Achieved SVR12
timeFrame: 3 months
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
Study officials:
affiliation: Kyushu University Hospital
name: Norihiro Furusyo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.