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

• Sponsor: Kaohsiung Medical University Chung-Ho Memorial Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03042520
• Collaborator: Chang Gung Memorial Hospital (Other), National Taiwan University Hospital (Other), National Cheng-Kung University Hospital (Other), Chi Mei Medical Hospital (Other), China Medical University, China (Other), Mackay Memorial Hospital (Other), Taipei Veterans General Hospital, Taiwan (Other), Changhua Christian Hospital (Other), Pusan National University Hospital (Other), Asan Medical Center (Other), Korea University (Other), Inje University (Other), Korea University Guro Hospital (Other), Kyungpook National University Hospital (Other), Seoul National University Hospital (Other), Severance Hospital (Other), Samsung Medical Center (Other), Seoul National University Bundang Hospital (Other), Soon Chun Hyang University (Other), Seoul St. Mary's Hospital (Other), Gachon University Gil Medical Center (Other), Dong-A University Hospital (Other), Gangnam Severance Hospital (Other)
• Enrollment: 200
• Locations: 26
• Anticipated Duration (Months): 73
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Fibroses; HepatoCellular Carcinoma; Cryoglobulinemia; Metabolic Disease; Diabetes Mellitus	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 Design

• Study Type: Observational
• Anticipated Enrollment: 200 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Long-term Hepatic and Extra-hepatic Outcomes of Chronic Hepatitis C Patients Post Sofosbuvir-based Interferon-free Treatment (LONGHEAD Study)
• Actual Study Start Date: Aug 1, 2016
• Anticipated Primary Completion Date: Sep 1, 2022
• Anticipated Study Completion Date: Sep 1, 2022

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. Number of participants with liver-related morbidity development during 5-year follow-up period after sofosbuvir-based treatment [6 years]

   Number of participants with liver-related morbidity during 5-year follow-up period after sofosbuvir-based treatment, including liver fibrosis progression and decompensation

2. Number of participants with liver-related mortality development during 5-year follow-up period after sofosbuvir-based treatment [6 years]

   Number of participants with liver-related mortality assessed by death due to HCC and/or liver decompensation

3. Number of participants with hepatocellular carcinoma (HCC) development during 5-year follow-up period after sofosbuvir-based treatment [6 years]

   Number of participants with HCC assessed by histocytology or positive dynamic image plus alpha fetoprotein (AFP) > 400 ng/ml

Secondary Outcome Measures

1. Life quality [6 years]

   The change of short form(SF)-36 from baseline

2. Cryoglobulinemia [6 years]

   Change of proportion of participants with cryoglobulinemia from baseline cryoglobulinemia from baseline)

3. Diabetes mellitus (DM) [6 years]

   Number of participants without DM develop DM assessed by Ac sugar > 126 g/ml

4. Insulin resistance [6 years]

   Change of homeostatic model assessment (HOMA-IR), assessed by Glucose x insulin/22.5 from baseline

5. Lipid profiles [6 years]

   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. Renal disease [6 years]

   the change of the estimated glomerular filtration rate (eGFR) from baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Korea University Ansan Hospital	Ansan		Korea, Republic of
2	Asan Medical Center	Asan		Korea, Republic of
3	Soon Chun Hyang University Hospital Bucheon.	Bucheon		Korea, Republic of
4	Dong-A University Hospital	Busan		Korea, Republic of
5	Inje University Busan Paik Hospital	Busan		Korea, Republic of
6	Kyungpook National University Hospital	Daegu		Korea, Republic of
7	Gachon University Gil Hospital	Incheon		Korea, Republic of
8	Pusan National University Hospital	Pusan		Korea, Republic of
9	Gangnam Severance Hospital	Seoul		Korea, Republic of
10	Korea University Guro Hospital	Seoul		Korea, Republic of
11	Samsung Medical Center	Seoul		Korea, Republic of
12	Seoul National University Bundang Hosptial	Seoul		Korea, Republic of
13	Seoul National University Hospital	Seoul		Korea, Republic of
14	Seoul St. Mary's Hospital	Seoul		Korea, Republic of
15	Severance Hospital	Seoul		Korea, Republic of
16	Changhua Christian Hospital	Changhua		Taiwan
17	Kaoshiung Medical University Hospital	Kaohsiung City		Taiwan
18	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan
19	Keelung Chang Gung Memorial Hospital	Keelung		Taiwan
20	China Medical University	Taichung		Taiwan
21	Chi Mei Liouying Hospital	Tainan		Taiwan
22	MacKay Memorial Hospital	Taipei		Taiwan
23	National Cheng Kung University Hospital	Taipei		Taiwan
24	National Taiwan University Hospital	Taipei		Taiwan
25	Taipei Veterans General Hospital	Taipei		Taiwan
26	Linkou Chang Gung Memorial Hospital	Taoyuan		Taiwan

Sponsors and Collaborators

• Kaohsiung Medical University Chung-Ho Memorial Hospital
• Chang Gung Memorial Hospital
• National Taiwan University Hospital
• National Cheng-Kung University Hospital
• Chi Mei Medical Hospital
• China Medical University, China
• Mackay Memorial Hospital
• Taipei Veterans General Hospital, Taiwan
• Changhua Christian Hospital
• Pusan National University Hospital
• Asan Medical Center
• Korea University
• Inje University
• Korea University Guro Hospital
• Kyungpook National University Hospital
• Seoul National University Hospital
• Severance Hospital
• Samsung Medical Center
• Seoul National University Bundang Hospital
• Soon Chun Hyang University
• Seoul St. Mary's Hospital
• Gachon University Gil Medical Center
• Dong-A University Hospital
• Gangnam Severance Hospital

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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kaohsiung Medical University Chung-Ho Memorial Hospital
• ClinicalTrials.gov Identifier: NCT03042520
• Other Study ID Numbers: irb20160082
• First Posted: Feb 3, 2017
• Last Update Posted: Oct 12, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Hepatitis C; Hepatitis C, Chronic; Liver Cirrhosis; Cryoglobulinemia; Metabolic Diseases

Study Results

No Results Posted as of Oct 12, 2021