A Real-World Study of Pegylated Interferon In Nucleoside-treated Patients With Chronic Hepatitis B
- Conditions
- Chronic Hepatitis B
- Interventions
- Registration Number
- NCT03357822
- Lead Sponsor
- Tongji Hospital
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 2000
- Male and female patients from 18 to 65 years of age;
- HBsAg positive, entecavir and or adefovir dipivoxil are used at least 1 year including patients with nucleotides or nucleoside resistance history;
- Before nucleotides or nucleosides treatment, ALT > 2 upper limit of normal value (ULN), HBV DNA >10000 copies/ml, HBsAg positive;
- Serum HBV DNA ≤ 500 copies/ml;
- HBsAg<3000 IU/ml;
- HBsAg positive;
- 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;
- Absence of cirrhosis confirmed by ultrasonic test;
- Agree to participate in the study and sign the patient informed consent.
- HBV DNA > 500 copies/ml;
- 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;
- Women with ongoing pregnancy or breast-feeding;
- 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);
- ALT >10 ULN;
- 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:
- one of the following 5 conditions are met, the patient has to be excluded:
- Serum albumin < 3.5 g/L;
- Prothrombin time > 3 seconds prolonged;
- Serum bilirubin > 34 µ mol/L;
- History of encephalopathy;
- History of variceal bleeding;
- Ascites;
- 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);
- 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;
- Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening;
- Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men;
- Serum creatinine level > 1.5 ULN in screening period.
- Phosphorus < 0.65 mmol/L;
- antinuclear antibody (ANA) > 1:100;
- 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;
- History of a severe seizure disorder or current anticonvulsant use;
- History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.);
- History of chronic pulmonary disease associated with functional limitation;
- Diseases that interferon and nucleotides or nucleosides are not suitable.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sequential combination therapy group Tenofovir disoproxil fumarate 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 Nucleoside therapy group Entecavir Patients are treated with entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 96 weeks Sequential combination therapy group Pegylated interferon 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 Sequential combination therapy group Entecavir 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 Nucleoside therapy group Tenofovir disoproxil fumarate Patients are treated with entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 96 weeks
- Primary Outcome Measures
Name Time Method HBsAg loss rate at week 48 Percentages of patients who achieve HBsAg loss at week 48
- Secondary Outcome Measures
Name Time Method sustained HBsAg loss rate at week 120 Percentages of patients who achieve HBsAg loss at week 120
decline in HBsAg level at week 96 Decline in HBsAg level from baseline to week 96
HBsAb appearance rate at week 96 Percentages of HBsAb appearance at week 96
Rate of alanine aminotransferase (ALT) normalization at week 96 Percentages of ALT normalization at week 96
The rate of progression to cirrhosis at week 120 The rate of progression to cirrhosis at week 120
The incidence rate of hepatocarcinoma at week 120 The incidence rate of hepatocarcinoma at week 120
HBsAb seroconversion rate at week 96 Percentages of HBsAb seroconversion at week 96
HBeAg loss rate at week 96 Percentages of HBeAg loss in the HBeAg-positive patients at week 96
HBeAg seroconversion rate at week 96 Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 96
Rate of HBV DNA level <1000 copies/mL at week 96 Percentages of HBV DNA level \<1000 copies/mL at week 96
HBsAg level at week 96 Dynamic change in HBsAg level from baseline to week 96
HBsAg loss rate at week 96 Percentages of patients who achieve HBsAg loss at week 96
Trial Locations
- Locations (12)
BeiJing YouAn Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
The First Hospital Affiliated to AMU
🇨🇳Chongqing, Chongqing, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Departmen of infectious disease, Xiangya Hospital, Central-south Universit
🇨🇳Changsha, Hunan, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Traditional Chinese Medicine,Xiamen Hospital
🇨🇳Shantou, Xiamen, China
The First Affiliated Hospital with Nanjing Medical University
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of College of Medicine, Zhejiang University
🇨🇳Zhejiang, Hangzhou, China
The first affiliated hospital of Wenzhou medical universtiy
🇨🇳Wenzhou, Zhejiang, China
302 Military Hospital of China
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
The Second Hospital of Nanjing
🇨🇳Nanjing, Jiangsu, China