A Real-World Study of Pegylated Interferon In Nucleoside-treated Patients With Chronic Hepatitis B (COST)

April 23, 2018 updated by: Qin Ning, Tongji Hospital

A Real-World Study of Sequential Combination Therapy With Pegylated Interferon In Nucleoside-treated Patients With Chronic Hepatitis B

The aim of the prospective real-world study is to evaluate whether sequential combination therapy with pegylated interferon plus entecavir/tenofovir could induce higher rates of HBsAg loss in nucleoside-treated patients with chronic hepatitis B compared to continuous nucleoside treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Patents who were treated with NA at least one year and achieved hepatitis B virus (HBV) DNA suppression and HBsAg level<3000 international unit (IU) /mL are enrolled in this study, they are assigned into two groups, in group I, patients will receive pegylated interferon plus entecavir/tenofovir for 48/72/96 weeks, in group II, patients will receive entecavir/tenofovir for 96 weeks. HBsAg loss rates at the end of treatment and sustained response at the end of follow up will be evaluated.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2000

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • Not yet recruiting
        • Beijing Youan Hospital, Capital Medical University
        • Contact:
          • Xinyue Chen, Doctor
      • Beijing, Beijing, China
        • Recruiting
        • 302 Military Hospital of China
        • Contact:
          • Junliang Fu
    • Chongqing
      • Chongqing, Chongqing, China
        • Not yet recruiting
        • The First Hospital Affiliated To AMU
        • Contact:
          • Xuqing Zhang
    • Fujian
      • Fuzhou, Fujian, China
        • Not yet recruiting
        • The First Affiliated Hospital of Fujian Medical University
        • Contact:
          • Jiaji Jiang, Doctor
    • Guangxi
      • Nanning, Guangxi, China
        • Not yet recruiting
        • The First Affiliated Hospital of Guangxi Medical University
    • Hangzhou
      • Zhejiang, Hangzhou, China, Doctor
        • Not yet recruiting
        • The First Affiliated Hospital of College of Medicine, Zhejiang University
        • Contact:
          • Qi Xia
    • Hunan
      • Changsha, Hunan, China
        • Not yet recruiting
        • The Second Xiangya Hospital of Central South University
        • Contact:
          • Guozhong Gong
      • Changsha, Hunan, China
        • Not yet recruiting
        • Departmen of infectious disease, Xiangya Hospital, Central-south Universit
        • Contact:
          • Deming Tan, Doctor
    • Jiangsu
      • Nanjing, Jiangsu, China
        • Not yet recruiting
        • The First Affiliated Hospital with Nanjing Medical University
        • Contact:
          • Chuanlong zhu
      • Nanjing, Jiangsu, China
        • Not yet recruiting
        • The Second Hospital of Nanjing
        • Contact:
          • Wei Zhao
    • Xiamen
      • Shantou, Xiamen, China
        • Not yet recruiting
        • Traditional Chinese Medicine,Xiamen Hospital
        • Contact:
          • Qianguo Mao
    • Zhejiang
      • Wenzhou, Zhejiang, China
        • Not yet recruiting
        • The first affiliated hospital of Wenzhou medical universtiy
        • Contact:
          • Yongping Chen, Doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male and female patients from 18 to 65 years of age;
  2. HBsAg positive, entecavir and or adefovir dipivoxil are used at least 1 year including patients with nucleotides or nucleoside resistance history;
  3. Before nucleotides or nucleosides treatment, ALT > 2 upper limit of normal value (ULN), HBV DNA >10000 copies/ml, HBsAg positive;
  4. Serum HBV DNA ≤ 500 copies/ml;
  5. HBsAg<3000 IU/ml;
  6. HBsAg positive;
  7. Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug;
  8. Absence of cirrhosis confirmed by ultrasonic test;
  9. Agree to participate in the study and sign the patient informed consent.

Exclusion Criteria:

  1. HBV DNA > 500 copies/ml;
  2. Other antiviral, anti-neoplastic or immunomodulatory treatment (including supra physiologic doses of steroids and radiation) 6 months prior to the first dose of randomized treatment (except for 7 days of acyclovir for herpetic lesions more than 1 month prior to first administration of randomized treatment). Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation are also excluded;
  3. Women with ongoing pregnancy or breast-feeding;
  4. Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals which have the ability to do the test will do) and/or human immunodeficiency virus (HIV);
  5. ALT >10 ULN;
  6. Evidence of decompensated liver disease (Child-Pugh score > 5). Child-Pugh > 5 means, if one of the following 5 conditions are met, the patient has to be excluded:
  7. one of the following 5 conditions are met, the patient has to be excluded:
  8. Serum albumin < 3.5 g/L;
  9. Prothrombin time > 3 seconds prolonged;
  10. Serum bilirubin > 34 µ mol/L;
  11. History of encephalopathy;
  12. History of variceal bleeding;
  13. Ascites;
  14. History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia);
  15. Signs or symptoms of hepatocellular carcinoma, patients with a value of alpha-fetoprotein > 100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months. Patients with values < 20 ng/mL but > 100 ng/mL may be enrolled, if hepatic neoplasia has been excluded by liver imaging;
  16. Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening;
  17. Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men;
  18. Serum creatinine level > 1.5 ULN in screening period.
  19. Phosphorus < 0.65 mmol/L;
  20. antinuclear antibody (ANA) > 1:100;
  21. History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease;
  22. History of a severe seizure disorder or current anticonvulsant use;
  23. History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.);
  24. History of chronic pulmonary disease associated with functional limitation;
  25. Diseases that interferon and nucleotides or nucleosides are not suitable.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sequential combination therapy group
Patients are treated with pegylated Interferon (180ug, subcutaneously, once a week) plus entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 48/72/96 weeks
Drug: Pegylated interferon
180ug Pegylated interferon is injected subcutaneously once a week
Other Names:
  • Pegylated interferon (PegIFN)
Drug: Entecavir
0.5mg entecavir is orally taken every day
Other Names:
  • Entecavir (ETV)
Drug: Tenofovir disoproxil fumarate
300mg tenofovir is orally taken every day
Other Names:
  • Tenofovir disoproxil fumarate (TDF)
Active Comparator: Nucleoside therapy group
Patients are treated with entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 96 weeks
Drug: Entecavir
0.5mg entecavir is orally taken every day
Other Names:
  • Entecavir (ETV)
Drug: Tenofovir disoproxil fumarate
300mg tenofovir is orally taken every day
Other Names:
  • Tenofovir disoproxil fumarate (TDF)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
HBsAg loss rate
Time Frame: at week 48
Percentages of patients who achieve HBsAg loss at week 48
at week 48

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
HBsAg loss rate
Time Frame: at week 72
Percentages of patients who achieve HBsAg loss at week 72
at week 72
HBsAg loss rate
Time Frame: at week 96
Percentages of patients who achieve HBsAg loss at week 96
at week 96
HBsAg level
Time Frame: at week 48
Dynamic change in HBsAg level from baseline to week 48
at week 48
HBsAg level
Time Frame: at week 72
Dynamic change in HBsAg level from baseline to week 72
at week 72
HBsAg level
Time Frame: at week 96
Dynamic change in HBsAg level from baseline to week 96
at week 96
sustained HBsAg loss rate
Time Frame: at week 120
Percentages of patients who achieve HBsAg loss at week 120
at week 120
decline in HBsAg level
Time Frame: at week 48
Decline in HBsAg level from baseline to week 48
at week 48
decline in HBsAg level
Time Frame: at week 72
Decline in HBsAg level from baseline to week 72
at week 72
decline in HBsAg level
Time Frame: at week 96
Decline in HBsAg level from baseline to week 96
at week 96
HBsAb appearance rate
Time Frame: at week 48
Percentages of HBsAb appearance at week 48
at week 48
HBsAb appearance rate
Time Frame: at week 72
Percentages of HBsAb appearance at week 72
at week 72
HBsAb appearance rate
Time Frame: at week 96
Percentages of HBsAb appearance at week 96
at week 96
HBsAb seroconversion rate
Time Frame: at week 48
Percentages of HBsAb seroconversion at week 48
at week 48
HBsAb seroconversion rate
Time Frame: at week 72
Percentages of HBsAb seroconversion at week 72
at week 72
HBsAb seroconversion rate
Time Frame: at week 96
Percentages of HBsAb seroconversion at week 96
at week 96
HBeAg loss rate
Time Frame: at week 48
Percentages of HBeAg loss in the HBeAg-positive patients at week 48
at week 48
HBeAg loss rate
Time Frame: at week 72
Percentages of HBeAg loss in the HBeAg-positive patients at week 72
at week 72
HBeAg loss rate
Time Frame: at week 96
Percentages of HBeAg loss in the HBeAg-positive patients at week 96
at week 96
HBeAg seroconversion rate
Time Frame: at week 48
Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 48
at week 48
HBeAg seroconversion rate
Time Frame: at week 72
Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 72
at week 72
HBeAg seroconversion rate
Time Frame: at week 96
Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 96
at week 96
Rate of HBV DNA level <1000 copies/mL
Time Frame: at week 96
Percentages of HBV DNA level <1000 copies/mL at week 96
at week 96
Rate of alanine aminotransferase (ALT) normalization
Time Frame: at week 96
Percentages of ALT normalization at week 96
at week 96
The rate of progression to cirrhosis
Time Frame: at week 120
The rate of progression to cirrhosis at week 120
at week 120
The incidence rate of hepatocarcinoma
Time Frame: at week 120
The incidence rate of hepatocarcinoma at week 120
at week 120

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tongji Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Qin Ning, Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 25, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 25, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 25, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 20, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 24, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 30, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 25, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • COST study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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