Long-term Outcomes of Chronic Hepatitis C Patients Post Sofosbuvir-based Treatment (LONGHEAD)

Long-term Hepatic and Extra-hepatic Outcomes of Chronic Hepatitis C Patients Post Sofosbuvir-based Interferon-free Treatment (LONGHEAD Study)

Primary Objective:

To evaluate the long-term outcomes including liver related morbidity, mortality and hepatocellular carcinoma (HCC) development as compared to those of historical control with interferon(IFN)-based treatment.

Secondary Objective:

1. To access liver fibrosis progression/regression in CHC patients after sofosbuvir-based treatment.
2. To investigate the long-term outcomes of extrahepatic manifestations of the sofosbuvir-based treated cohort as compared to their pretreatment status.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus; Metabolic Disease; Cryoglobulinemia; HepatoCellular Carcinoma; Liver Fibroses
• Intervention / Treatment: Other: Observation only

Detailed Description

Primary Endpoint:

To evaluate the long-term event-free effect after sofosbuvir-based therapy, in terms of free of major liver events (including HCC, decompensation with ascites, variceal bleeding, hepatic encephalopathy, and liver-related mortality) in CHC patients.

Secondary Endpoints:

1. To evaluate hepatic fibrosis progression or regression in CHC patients after sofosbuvir-based therapy.
2. To evaluate the durability of sustained viral response (SVR) in patients achieving SVR after sofosbuvir-based therapy.
3. To evaluate long-term effect of sofosbuvir-based therapy on the extra-hepatic manifestations of the cohort. The items include mixed cryoglobulinemia, chronic kidney diseases, insulin resistance, diabetic status, cardiovascular events and dyslipidemia.
4. To evaluate long-term effect of sofosbuvir-based therapy on quality of life on the cohort.

Study Design Prospective, longitudinal observational study

Study procedure A total of 200 patients receiving sofosbuvir based direct antiviral agents (DAAs) in the parent studies will be included for following up to 5 years. Their serological, image study and disease status description will be prospectively documented to present the long term effects of sofosbuvir-based therapy.

The presentation of illness will be specified as:

1. Main hepatic complications as liver fibrosis, hepatic malignancy, liver decompensation with ascites, hepatic encephalopathy and variceal bleeding, and liver-related mortality.
2. Life quality, extrahepatic symptoms as cryoglobulinemia, diabetes mellitus, insulin resistance, lipid profiles, renal insufficiency and other non-liver morbidities and malignancy.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Wan-Long Chuang; Phone Number: 0975-356064; Email: waloch@kmu.edu.tw

Study Locations

• Korea, Republic of
  • Ansan, Korea, Republic of
    • Recruiting
    • Korea University Ansan Hospital
    • Contact: Hyung Joon Yim
  • Asan, Korea, Republic of
    • Recruiting
    • Asan Medical Center
    • Contact: Young-Suk Lim
  • Bucheon, Korea, Republic of
    • Recruiting
    • Soon Chun Hyang University Hospital Bucheon.
    • Contact: Young Seok Kim
  • Busan, Korea, Republic of
    • Recruiting
    • Inje University Busan Paik Hospital
    • Contact: Youn-Jae Lee
  • Busan, Korea, Republic of
    • Recruiting
    • Dong-A University Hospital
    • Contact: Sang-Young Han
  • Daegu, Korea, Republic of
    • Recruiting
    • Kyungpook National University Hospital
    • Contact: Won Young Tak
  • Incheon, Korea, Republic of
    • Recruiting
    • Gachon University Gil Hospital
    • Contact: Ju-Hyun Kim
  • Pusan, Korea, Republic of
    • Recruiting
    • Pusan National University Hospital
    • Contact: Heo Jeong
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: Kwan Soo Byun
  • Seoul, Korea, Republic of
    • Recruiting
    • Gangnam Severance Hospital
    • Contact: Kwan Sik Lee
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital
    • Contact: Sang Hoon Ahn
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
    • Contact: Seung Woon Paik
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul st. mary's hospital
    • Contact: Seung-Kew Yoon
  • Seoul, Korea, Republic of
    • Recruiting
    • Korea University Guro Hospital
    • Contact: Yoon Jun Kim
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Bundang Hosptial
    • Contact: Sook-Hyang Jeong
• Taiwan
  • Changhua, Taiwan
    • Recruiting
    • Changhua Christian Hospital
    • Contact: Yu-Chun Hsu
  • Kaohsiung, Taiwan
    • Recruiting
    • Kaohsiung Chang Gung Memorial Hospital
    • Contact: Tsung-Hui Hu
  • Kaohsiung City, Taiwan
    • Recruiting
    • Kaoshiung Medical University Hospital
    • Contact: Wan-Long Chuang; Phone Number: 0975-356064; Email: waloch@kmu.edu.tw
  • Keelung, Taiwan
    • Recruiting
    • Keelung Chang Gung Memorial Hospital
    • Contact: Rong-Nan Chien
  • Taichung, Taiwan
    • Recruiting
    • China Medical University
    • Contact: Cheng-Yuan Peng
  • Tainan, Taiwan
    • Recruiting
    • Chi Mei Liouying Hospital
    • Contact: Chih-Chou Chen
  • Taipei, Taiwan
    • Recruiting
    • Mackay Memorial Hospital
    • Contact: Horng-Yuan Wang
  • Taipei, Taiwan
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: Chi-Jen Chu
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Jia-Horng Kao
  • Taipei, Taiwan
    • Recruiting
    • National Cheng Kung University Hospital
    • Contact: Ting-Tsung Chang
  • Taoyuan, Taiwan
    • Recruiting
    • Linkou Chang Gung Memorial Hospital
    • Contact: I-Shyan Sheen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who had ever participated the parent studies, GS-US-334-0115 or GS-US-337-0131, will be invited to participate the current study in outpatient clinic. For the patients who have participated study will be invited to participate the current study as matched historical control n our outpatient clinic, Written informed consent will be obtained after full explanation to the patients who had ever participated in parent studies, GS-US-337-0131 (NCT02021656) or GS-US-334-0115 (NCT02021643) and had received at least one dose of sofosbuvir-based therapy in the parent studies.

Description

Main inclusion criteria:

For Sofosbuvir-based therapy observational group:

• Patients ≥ 20 of years who had ever participated in parent studies, GS-US-337-0131 (NCT02021656) or GS-US-334-0115 (NCT02021643)
• Patients who had received at least one dose of sofosbuvir-based therapy in the parent studies.

Who IFN-based therapy historical controls, matched with sex, age, level of liver fibrosis and virological response:

• Patients ≥ 20 of years who had received pegylated interferon plus ribavirin therapy with match of sex, age, level of liver fibrosis and virological response
• Patients who have ever participated study will be collected as historical control.

Main exclusion criteria:

• Patients not qualified by the main inclusion criteria were excluded.

For Sofosbuvir-based therapy observational group:

• Patients < 20 of years
• Patients who are unwilling to participate the current study
• Patients who had never participated in parent studies, GS-US-337-0131 (NCT02021656) nor GS-US-334-0115 (NCT02021643)
• Patients who had never received at least one dose of sofosbuvir-based therapy in the parent studies.

Who IFN-based therapy historical controls:

• Patients < 20 of years
• Patients who are unwilling to participate the current study
• Patients who had never received pegylated interferon plus ribavirin therapy
• Patients who did not participate study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
IFN-based therapy historical controls; Patients who had ever participated the parent studies, GS-US-334-0115 or GS-US-337-0131, will be invited to participate the current study in outpatient clinic. For the patients who have participated study will be invited to participate the current study as matched historical control n our outpatient clinic,	Other: Observation only
Sofosbuvir-based therapy observational group; Patients ≥ 20 of years who had ever participated in parent studies, GS-US-337-0131 (NCT02021656) or GS-US-334-0115 (NCT02021643); Patients who had received at least one dose of sofosbuvir-based therapy in the parent studies. Who IFN-based therapy historical controls, matched with sex, age, level of liver fibrosis and virological response: Patients ≥ 20 of years who had received peginterferon plus ribavirin therapy with match of sex, age, level of liver fibrosis and virological response; Patients who have ever participated study will be collected as historical control.	Other: Observation only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with liver-related morbidity development during 5-year follow-up period after sofosbuvir-based treatment	Number of participants with liver-related morbidity during 5-year follow-up period after sofosbuvir-based treatment, including liver fibrosis progression and decompensation	6 years
Number of participants with liver-related mortality development during 5-year follow-up period after sofosbuvir-based treatment	Number of participants with liver-related mortality assessed by death due to HCC and/or liver decompensation	6 years
Number of participants with hepatocellular carcinoma (HCC) development during 5-year follow-up period after sofosbuvir-based treatment	Number of participants with HCC assessed by histocytology or positive dynamic image plus alpha fetoprotein (AFP) > 400 ng/ml	6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Life quality	The change of short form(SF)-36 from baseline	6 years
Cryoglobulinemia	Change of proportion of participants with cryoglobulinemia from baseline cryoglobulinemia from baseline)	6 years
Diabetes mellitus (DM)	Number of participants without DM develop DM assessed by Ac sugar > 126 g/ml	6 years
Insulin resistance	Change of homeostatic model assessment (HOMA-IR), assessed by Glucose x insulin/22.5 from baseline	6 years
Lipid profiles	Change of the serum profile of lipids including triglyceride(TG), cholesterol(Chol), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) from baseline	6 years
Renal disease	the change of the estimated glomerular filtration rate (eGFR) from baseline	6 years

Collaborators and Investigators

• Sponsor: Kaohsiung Medical University Chung-Ho Memorial Hospital
• Collaborators: National Taiwan University Hospital; China Medical University, China; Mackay Memorial Hospital; Samsung Medical Center; Seoul St. Mary's Hospital; Pusan National University Hospital; Asan Medical Center; Chang Gung Memorial Hospital; Seoul National University Hospital; Taipei Veterans General Hospital, Taiwan; Seoul National University Bundang Hospital; Korea University Guro Hospital; Korea University; National Cheng-Kung University Hospital; Gachon University Gil Medical Center; Kyungpook National University Hospital; Inje University; Gangnam Severance Hospital; Severance Hospital; Changhua Christian Hospital; Chi Mei Medical Hospital; Dong-A University Hospital; Soon Chun Hyang University
• Investigators: Study Director: Ming-Lung Yu, Kaoshiung Medical University Hospital; Principal Investigator: Chia-Yen Dai, Kaoshiung Medical University Hospital; Principal Investigator: Jee-Fu Huang, Kaoshiung Medical University Hospital; Principal Investigator: Chung-Feng Huang, Kaoshiung Medical University Hospital; Principal Investigator: Ming-Lun Yeh, Kaoshiung Medical University Hospital; Principal Investigator: Ching-I Huang, Kaoshiung Medical University Hospital; Principal Investigator: Ta-Wei Liu, Kaoshiung Medical University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: December 21, 2016
• First Submitted That Met QC Criteria: February 1, 2017
• First Posted (Estimate): February 3, 2017

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 10, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Immune System Diseases; Immunoproliferative Disorders; Hematologic Diseases; Liver Diseases; Hemorrhagic Disorders; Flaviviridae Infections; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hepatitis, Viral, Human; Hepatitis, Chronic; Fibrosis; Hepatitis; Hepatitis C; Liver Cirrhosis; Hepatitis C, Chronic; Metabolic Diseases; Cryoglobulinemia
• Other Study ID Numbers: irb20160082

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No