Clinical trial NCT03042520: Long-term Outcomes of Chronic Hepatitis C Patients Post Sofosbuvir-based Treatment
Official title: Long-term Hepatic and Extra-hepatic Outcomes of Chronic Hepatitis C Patients Post Sofosbuvir-based Interferon-free Treatment (LONGHEAD Study)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Liver Fibroses
HepatoCellular Carcinoma
Cryoglobulinemia
Metabolic Disease
Diabetes Mellitus
Lead sponsor: Kaohsiung Medical University Chung-Ho Memorial Hospital
Sponsor class: OTHER
Collaborators: name: Chang Gung Memorial Hospital
name: National Taiwan University Hospital
name: National Cheng-Kung University Hospital
name: Chi Mei Medical Hospital
name: China Medical University, China
name: Mackay Memorial Hospital
name: Taipei Veterans General Hospital, Taiwan
name: Changhua Christian Hospital
name: Pusan National University Hospital
name: Asan Medical Center
name: Korea University
name: Inje University
name: Korea University Guro Hospital
name: Kyungpook National University Hospital
name: Seoul National University Hospital
name: Severance Hospital
name: Samsung Medical Center
name: Seoul National University Bundang Hospital
name: Soon Chun Hyang University
name: Seoul St. Mary's Hospital
name: Gachon University Gil Medical Center
name: Dong-A University Hospital
name: Gangnam Severance Hospital
First posted: 2017-02-03
Enrollment: 200
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with liver-related morbidity development during 5-year follow-up period after sofosbuvir-based treatment
timeFrame: 6 years
measure: Number of participants with liver-related mortality development during 5-year follow-up period after sofosbuvir-based treatment
timeFrame: 6 years
measure: Number of participants with hepatocellular carcinoma (HCC) development during 5-year follow-up period after sofosbuvir-based treatment
timeFrame: 6 years
Secondary outcomes:
measure: Life quality
timeFrame: 6 years
measure: Cryoglobulinemia
timeFrame: 6 years
measure: Diabetes mellitus (DM)
timeFrame: 6 years
measure: Insulin resistance
timeFrame: 6 years
measure: Lipid profiles
timeFrame: 6 years
measure: Renal disease
timeFrame: 6 years
Other outcomes:
Locations:
city: Ansan
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Asan
country: Korea, Republic of
facility: Asan Medical Center
city: Bucheon
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon.
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Hospital
city: Pusan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hosptial
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung City
country: Taiwan
facility: Kaoshiung Medical University Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Keelung
country: Taiwan
facility: Keelung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University
city: Tainan
country: Taiwan
facility: Chi Mei Liouying Hospital
city: Taipei
country: Taiwan
facility: MacKay Memorial Hospital
city: Taipei
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: Kaoshiung Medical University Hospital
name: Ming-Lung Yu
role: STUDY_DIRECTOR
affiliation: Kaoshiung Medical University Hospital
name: Chia-Yen Dai
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaoshiung Medical University Hospital
name: Jee-Fu Huang
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaoshiung Medical University Hospital
name: Chung-Feng Huang
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaoshiung Medical University Hospital
name: Ming-Lun Yeh
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaoshiung Medical University Hospital
name: Ching-I Huang
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaoshiung Medical University Hospital
name: Ta-Wei Liu
role: PRINCIPAL_INVESTIGATOR
References: