Regression of Liver Fibrosis After Daclatasvir and Asunaprevir Treatment

Chronic Hepatitis C Clinical Trial

— RELIF-C  

Official title:

Regression of Liver Fibrosis Assessed by Transient Elastography After Daclatasvir and Asunaprevir Combined Treatment in Advanced Fibrotic/Cirrhotic Patients With Chronic Hepatitis C Genotype 1b Infection

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02865369
• Other study ID #: AI444-392
• Status: Not yet recruiting
• Phase: N/A
• First received: August 3, 2016
• Last updated: March 4, 2017
• Start date: September 2016
• Est. completion date: December 2022

Study information

• Verified date: March 2017
• Source: Soonchunhyang University Hospital
• Contact: Sang Gyune Kim, Professor
• Phone: 82-32-621-5071
• Email: mcnulty[@]schmc.ac.kr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

A study on regression of liver fibrosis assessed by transient elastography after Daclatasvir and Asunaprevir combined treatment in advanced fibrotic/cirrhotic patients with chronic hepatitis C genotype 1b Infection

Description:

The measurement of liver stiffness by transient elastography (TE) has been shown to correlate with the hepatic fibrosis stage and to have considerable accuracy for the diagnosis of cirrhosis in patients with chronic hepatitis C. Previous studied reported that liver stiffness is significantly reduced in SVR patients with pegylated interferon (IFN) and ribavirin treatment. Once a patient achieve sustained virological response (SVR), and resultingly lower liver stiffness score than baseline value, it is believed that he will have a better long-term outcome due to the improvement of liver fibrosis.

Daclatasvir(DCV) and Asunaprevir(ASV) combined treatment showed a greater SVR rate in CHC compared to IFN based therapy. The investigators hypothesize that DCV and ASV combined treatment may achieve the improvement of liver stiffness measured by TE and a more favorable clinical outcomes in patients with advanced liver fibrosis. The investigators will also compare the change of fibrosis stage assessed by TE between this study subjects and those treated with other DAA agents during same observational period.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 103
• Est. completion date: December 2022
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• Chronically infected with Hepatitis C virus genotype 1b

• HCV RNA = 10^4 IU/mL (10,000 IU/mL)

• Chronic Hepatitis C with advanced fibrosis or cirrhosis (defined as =F3, =8 kilopascals)

• Treatment-naïve or those who previously failed to treatment with peg-interferon alfa and ribavirin

• Women of childbearing potential (WOCBP) and men, who use effective methods of birth control

Exclusion Criteria:

• Patients with baseline key NS5A RAVs (Y93 and/or L31)

• Estimated GFR < 30mL/min without hemodialysis

• Alanine aminotransferase (ALT) > 100 IU/L

• Coinfection with other hepatitis virus or human immunodeficiency virus

• A daily alcohol intake >30 g

• Decompensated liver disease or hepatocellular carcinoma, liver or any other organ transplantation

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Fibrosis
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Liver Cirrhosis

Intervention

Drug:
• Daclatasvir and Asunaprevir
Daclatasvir and Asunaprevir combined treatment will not be assigned to the enrolled patients, but the patients who are treated with Daclatasvir and Asunaprevir will be included in this observational study.

Locations

Country	Name	City	State
Korea, Republic of	Korea University Ansan Hospital	Ansan	Gyeonggi-do
Korea, Republic of	Soon Chun Hyang University Bucheon Hospital	Bucheon	Gyeonggi do
Korea, Republic of	Soonchunhyang University Cheonan Hospital	Cheonan	Chungcheongnam-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Inha University Hospital	Jung-gu	Incheon
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Hanyang university hospital	Seoul
Korea, Republic of	Severance hospital	Seoul
Korea, Republic of	Soonchunhyang University Hospital	Seoul
Korea, Republic of	Wonju severance christian hospital	Wonju

Sponsors (9)

Lead Sponsor	Collaborator
Sang Gyune Kim	Bristol-Myers Squibb, Ewha Womans University Mokdong Hospital, Gachon University Gil Medical Center, Hanyang University Seoul Hospital, Inha University Hospital, Korea University, Seoul National University Boramae Hospital, Severance Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (6)

Arima Y, Kawabe N, Hashimoto S, Harata M, Nitta Y, Murao M, Nakano T, Shimazaki H, Kobayashi K, Ichino N, Osakabe K, Nishikawa T, Okumura A, Ishikawa T, Yoshioka K. Reduction of liver stiffness by interferon treatment in the patients with chronic hepatitis C. Hepatol Res. 2010 Apr;40(4):383-92. doi: 10.1111/j.1872-034X.2009.00618.x. — View Citation

Bourliere, Marc, et al.

Crisan D, Radu C, Grigorescu MD, Lupsor M, Feier D, Grigorescu M. Prospective non-invasive follow-up of liver fibrosis in patients with chronic hepatitis C. J Gastrointestin Liver Dis. 2012 Dec;21(4):375-82. — View Citation

Hézode C, Castéra L, Roudot-Thoraval F, Bouvier-Alias M, Rosa I, Roulot D, Leroy V, Mallat A, Pawlotsky JM. Liver stiffness diminishes with antiviral response in chronic hepatitis C. Aliment Pharmacol Ther. 2011 Sep;34(6):656-63. doi: 10.1111/j.1365-2036.2011.04765.x. — View Citation

Wang JH, Changchien CS, Hung CH, Tung WC, Kee KM, Chen CH, Hu TH, Lee CM, Lu SN. Liver stiffness decrease after effective antiviral therapy in patients with chronic hepatitis C: Longitudinal study using FibroScan. J Gastroenterol Hepatol. 2010 May;25(5):964-9. doi: 10.1111/j.1440-1746.2009.06194.x. — View Citation

Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Lédinghen V, Marcellin P, Dhumeaux D, Trinchet JC, Beaugrand M. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005 Jan;41(1):48-54. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change of liver fibrosis stage at 48 weeks assessed by transient elastography in patients treated with Daclatasvir and Asunaprevir	To compare the change of liver fibrosis stage (defined as F3, =8; F4, =12) assessed by transient elastography between baseline and 48 weeks in advanced fibrotic/cirrhotic Chronic Hepatitis C patients who achieved sustained virological response with Daclatasvir and Asunaprevir combined treatment	baseline to 48weeks
Secondary	Proportion of patients who were treated with Daclatasvir and Asunaprevir achieved SVR12 assessed by HCV RNA		baseline to 36 weeks
Secondary	Proportion of patients who maintained sustained virologic response at SVR24, SVR72, SVR120, SVR168, and SVR216.		baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
Secondary	The change of liver fibrosis stage assessed by transient elastography at 96weeks, 144weeks, 192weeks, 240weeks in patients treated with Daclatasvir and Asunaprevir		baseline to 96weeks, 144weeks, 192weeks, 240weeks
Secondary	The change of AST to Platelet Ratio Index	APRI = [(AST/upper limit of normal)/platelet count]x100	baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
Secondary	The change of Fibrosis 4 (Fib-4) index	FIB-4 = age (years) × AST [IU/L] / [platelet count × sqr(ALT [IU/L])]	baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
Secondary	Comparison of change of liver fibrosis stage assessed by transient elastography between Daclatasvir and Asunaprevir combined treatment versus other DAA treatment	Comparison of change of liver fibrosis stage assessed by transient elastography at 48weeks, 96weeks, 144weeks, 192weeks, 240weeks between Daclatasvir and Asunaprevir combined treatment versus other DAA treatment during same observational period	baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
Secondary	Comparison of the incidence of hepatocellular carcinoma or liver cirrhosis complications between Daclatasvir and Asunaprevir combined treatment versus other DAA treatment	Compare the incidence of hepatocellular carcinoma or liver cirrhosis complications at 48weeks, 96weeks, 144weeks, 192weeks, 240weeks between Daclatasvir and Asunaprevir combined treatment versus other Direct antiviral agents during same observational period	baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
Secondary	The change of Fibrometer score	alpha2 macroglobulin, GGT, AST, ALT, prothrombin index, urea, platelet count	baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks