Chronic Hepatitis CRELIF-CNCT02865369

Regression of Liver Fibrosis After Daclatasvir and Asunaprevir Treatment

An observational study of Chronic Hepatitis C, run by Sang Gyune Kim at 10 sites in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

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 Read more about this study

Who is it for?: Ages 19 years and older
Conditions the study is for: Chronic Hepatitis C
What is being tested?: Daclatasvir and Asunaprevir
How many people: 103 participants
Where: 10 sitesSouth Korea
Study dates: Sep 2016to Dec 2022
How long will I take part?: 5 Years
Phase: Observational
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 19 years and older
All sexes
No healthy volunteers
Adult, Older adult

Study population: Genotype 1b, advanced fibrotic/cirrhotic Korean patients with chronic hepatitis C aged over 18, without baseline NS5A RAVs (Y93 and/or L31)

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

10 sites in 1 country.

Sang Gyune Kim, Professor contact

82-32-621-5071

mcnulty@schmc.ac.kr

City, postcode or hospital

10 sites in 1 country

South Korea10 sites

Korea University Ansan Hospital
Ansan, Gyeonggi-do, 15355
Young Kul Jung, Professor
Young Kul Jung, Professor
Soon Chun Hyang University Bucheon Hospital
Bucheon-si, Gyeonggi-do, 14584
Sang Gyune Kim, Professor, 82-32-621-5079, mcnulty@schmc.ac.kr
Sang Gyune Kim
Soonchunhyang University Cheonan Hospital
Cheonan, Chungcheongnam-do, 31151
SaeHwan Lee, Professor
SaeHwan Lee, Professor
Gachon University Gil Medical Center
Incheon, 21565
Oh Sang Kwon, Professor
Oh Sang Kwon, Professor
Inha University Hospital
Jung-gu, Incheon, 22332
Jin-Woo Lee, Professor
Jin-Woo Lee, Professor
Severance hospital
Seoul, 03722
Jun Yong Park, Professor
Jun Yong Park, Professor
Soonchunhyang University Hospital
Seoul, 04401
Jae Young Jang, Professor
Jae Young Jang, Professor
Hanyang university hospital
Seoul, 04763
Dae Won Jun, Professor
Dae Won Jun, Professor
Ewha Womans University Mokdong Hospital
Seoul, 07985
Tae Hun Kim, Professor
Tae Hun Kim, Professor
Wonju severance christian hospital
Wŏnju, 26426
Moon young Kim, Professor
Moon young Kim, Professor

Other trials in South Korea

About this study

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

Read the detailed 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.

Conditions: Chronic Hepatitis C
Being tested: Daclatasvir and Asunaprevir
Keywords: chronic hepatitis C, Daclatasvir, Asunaprevir, fibrosis, transient elastography
Medical subject headings: Hepatitis C, Chronic, Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Daclatasvir and AsunaprevirDrug
Also called Daclatasvir and Asunaprevir combined treatment for 24 weeks
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.

Study groups in NCT02865369
Study group	Role	What they receive
Daclatasvir plus Asunaprevir treatment		Among patients taking Daclatasvir and Asunaprevir combined treatment and having advanced liver fibrosis assessed by transient elastography Receives: Drug: Daclatasvir and Asunaprevir

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: baseline to 48weeks

Secondary outcomes (8)

Proportion of patients who were treated with Daclatasvir and Asunaprevir achieved SVR12 assessed by HCV RNA
Measured: baseline to 36 weeks
Proportion of patients who maintained sustained virologic response at SVR24, SVR72, SVR120, SVR168, and SVR216.
Measured: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
The change of liver fibrosis stage assessed by transient elastography at 96weeks, 144weeks, 192weeks, 240weeks in patients treated with Daclatasvir and Asunaprevir
Measured: baseline to 96weeks, 144weeks, 192weeks, 240weeks
The change of AST to Platelet Ratio Index
APRI = [(AST/upper limit of normal)/platelet count]x100
Measured: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
The change of Fibrosis 4 (Fib-4) index
FIB-4 = age (years) × AST [IU/L] / [platelet count × sqr(ALT [IU/L])]
Measured: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
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
Measured: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
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
Measured: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
The change of Fibrometer score
alpha2 macroglobulin, GGT, AST, ALT, prothrombin index, urea, platelet count
Measured: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2016Dec 2022

First posted12 Aug 2016 (estimated)
Study startSep 2016
Primary completionDec 2018 (estimated)
Study completionDec 2022 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (7)Papers the sponsor has linked to this study.
Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 103 participants (estimated)
Target duration: 5 Years

IDs, dates and publications

ClinicalTrials.gov ID: NCT02865369
Sponsor's protocol ID: AI444-392
Acronym: RELIF-C
Status last verified: Mar 2017
First submitted: 3 Aug 2016
Last updated: 7 Mar 2017
Results posted: No
Data monitoring committee: No
Individual data sharing: No

Publications

Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Ledinghen 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. doi: 10.1002/hep.20506.
PubMed 15690481
Hezode C, Castera 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. Epub 2011 Jul 13.
PubMed 21752038
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. Epub 2010 Mar 4.
PubMed 20236358
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.
PubMed 20546451
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.
PubMed 23256120
Bourliere, Marc, et al.
Yoo HW, Park JY, Kim SG, Jung YK, Lee SH, Kim MY, Jun DW, Jang JY, Lee JW, Kwon OS. Regression of liver fibrosis and hepatocellular carcinoma development after HCV eradication with oral antiviral agents. Sci Rep. 2022 Jan 7;12(1):193. doi: 10.1038/s41598-021-03272-1.
PubMed 34996920

Want to know more?

Sang Gyune Kim, Professor

82-32-621-5071

mcnulty@schmc.ac.kr

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic

All Chronic Hepatitis C trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02865369
Acronym / sponsor ID: RELIF-C / AI444-392
Conditions: Chronic Hepatitis C
Keywords: chronic hepatitis C, Daclatasvir, Asunaprevir, fibrosis, transient elastography
Study type: Observational
Recruitment status: Unknown status
Enrolment: 103 participants (estimated)
Lead sponsor: Sang Gyune KimUniversity, hospital or other
Collaborators: Seoul National University Boramae Hospital, Severance Hospital, Inha University Hospital, Korea University, Gachon University Gil Medical Center, Hanyang University Seoul Hospital, Ewha Womans University Mokdong Hospital, Bristol-Myers Squibb
Study start: Sep 2016
Primary completion: Dec 2018 (estimated)
Study completion: Dec 2022 (estimated)
First posted: 12 Aug 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Target follow-up: 5 Years
Number of arms: 1

Arm	Type	Receives
Daclatasvir plus Asunaprevir treatment	–	Drug: Daclatasvir and AsunaprevirAmong patients taking Daclatasvir and Asunaprevir combined treatment and having advanced liver fibrosis assessed by transient elastography

Who may qualify

Ages: 19 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Genotype 1b, advanced fibrotic/cirrhotic Korean patients with chronic hepatitis C aged over 18, without baseline NS5A RAVs (Y93 and/or L31)

Key inclusion criteria (5 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Daclatasvir and AsunaprevirAlso: Daclatasvir and Asunaprevir combined treatment for 24 weeksDaclatasvir 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.	Drug	Daclatasvir plus Asunaprevir treatment

Primary outcome

The change of liver fibrosis stage at 48 weeks assessed by transient elastography in patients treated with Daclatasvir and Asunaprevir
Time frame: baseline to 48weeks
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

8 secondary outcomes

Proportion of patients who were treated with Daclatasvir and Asunaprevir achieved SVR12 assessed by HCV RNA
Time frame: baseline to 36 weeks
Proportion of patients who maintained sustained virologic response at SVR24, SVR72, SVR120, SVR168, and SVR216.
Time frame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
The change of liver fibrosis stage assessed by transient elastography at 96weeks, 144weeks, 192weeks, 240weeks in patients treated with Daclatasvir and Asunaprevir
Time frame: baseline to 96weeks, 144weeks, 192weeks, 240weeks
The change of AST to Platelet Ratio Index
Time frame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
The change of Fibrosis 4 (Fib-4) index
Time frame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
Comparison of change of liver fibrosis stage assessed by transient elastography between Daclatasvir and Asunaprevir combined treatment versus other DAA treatment
Time frame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
Comparison of the incidence of hepatocellular carcinoma or liver cirrhosis complications between Daclatasvir and Asunaprevir combined treatment versus other DAA treatment
Time frame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
The change of Fibrometer score
Time frame: baseline to 48weeks, 96weeks, 144weeks, 192weeks, 240weeks

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
Background: PubMed 15690481Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Ledinghen 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. doi: 10.1002/hep.20506.
Background: PubMed 21752038Hezode C, Castera 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. Epub 2011 Jul 13.
Background: PubMed 20236358Arima 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. Epub 2010 Mar 4.
Background: PubMed 20546451Wang 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.
Background: PubMed 23256120Crisan 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.
BackgroundBourliere, Marc, et al.
Derived from this study: PubMed 34996920Yoo HW, Park JY, Kim SG, Jung YK, Lee SH, Kim MY, Jun DW, Jang JY, Lee JW, Kwon OS. Regression of liver fibrosis and hepatocellular carcinoma development after HCV eradication with oral antiviral agents. Sci Rep. 2022 Jan 7;12(1):193. doi: 10.1038/s41598-021-03272-1.
Individual participant dataSharing planned: No

Related trials for Chronic Hepatitis C

RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sang Gyune Kim, Professor contact

82-32-621-5071

mcnulty@schmc.ac.kr

Sang Gyune Kim, Professor principal investigator

Soonchunhyang University Hospital

10 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Chronic Hepatitis C, run by Sang Gyune Kim at 10 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 7 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Sang Gyune Kim, Professor (82-32-621-5071, mcnulty@schmc.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The change of liver fibrosis stage at 48 weeks assessed by transient elastography in patients treated with Daclatasvir and Asunaprevir (time frame: baseline to 48weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02865369, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2017.