Clinical trial NCT02589652: Switch or Sequential Combination Therapy of Peginterferon in Hepatitis B Patients With Longterm Entecavir Therapy
Official title: Efficacy of Switch or Sequential Combination Therapy of Pegylated Interferon Alfa-2a in Chronic Hepatitis B Patients With Low HBsAg and HBeAg Titers After Long-term Entecavir Therapy: A Multicenter, Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Hepatitis B
Keywords: Pegylated interferon
Entecavir
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2015-10-28
Enrollment: 294
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Chronic Hepatitis B Patients with Low HBsAg and HBeAg Titers after Long-term Entecavir Therapy

Brief summary: This is a multicenter, prospective cohort study to evaluate the efficacy and safety of sequential combination or switch therapy of pegylated interferon alfa-2a in chronic hepatitis B patients with low HBsAg and HBeAg titers after long-term entecavir therapy, and compared to those who continued on ETV therapy.

Detailed description: Chronic hepatitis B (CHB) infection remains a global health treat. The ideal end point of therapy is HBsAg loss or HBsAg seroconversion, indicating a complete remission of CHB. In patients with HBeAg-positive CHB, sustained HBeAg seroconversion is also a desirable end point. Current therapies include pegylated interferon (PegIFN) finite and nucleos(t)ide analogues (NUCs) longterm therapy. However, only 30-40% of patients may achieve HBeAg seroconversion on PegIFN monotherapy, whereas 15-20% of patients on entecavir (ETV). Recently, accumulating evidence had shown that optimization of switching or combining PegIFN in patients on long-term ETV therapy may increase rate of HBeAg seroconversion and even lead to the complete eradication of HBV. However, these two regimens has not been tested adequately in patients with low HBsAg/HBeAg titers on long-term ETV therapy.

This is a multicenter, prospective cohort study to evaluate the efficacy and safety of sequential combination or switch therapy of pegylated interferon alfa-2a in chronic hepatitis B patients with low HBsAg and HBeAg titers after long-term entecavir therapy, and compared to those who continued on ETV therapy.

Eligibility criteria: Inclusion Criteria:

* Male and female patients \> 18 and ≤ 60 years of age;
* Positive HBsAg for more than 6 months;
* Patients receiving previous ETV therapy ≥2 years;
* Patients who have achieved undetectable HBV DNA, HBsAg \<1500IU/mL and HBeAg \<200S/CO prior to switch or S-C therapy;
* ALT\<=10\*ULN and TB\<2\*ULN;
* Patients who have been assigned to treatment with PegIFN (S-C or switch) or continuous ETV after previous ETV therapy

Exclusion Criteria:

* Evidence of decompensated cirrhosis or hepatocellular carcinoma;
* Serological evidence of co-infection with HCV, HDV or HIV;
* Pregnant or breast-feeding women;
* Patients with diseases that might contraindicate to PegIFN therapy including severe psychiatric diseases, immunological diseases, severe retinopathy, thyroid dysfunction, leukocytopenia, thrombopenia, etc
* Patients receiving concomitant therapy with telbivudine;
* A history of drug or alcohol abuse;
* Other conditions that investigates consider not suitable for participate

Primary outcomes:
measure: Rate of HBeAg seroconversion
timeFrame: week 72 (24 weeks after 48 weeks of treatment)
Secondary outcomes:
measure: Rate of HBsAg loss
timeFrame: week 72 (24 weeks after 48 weeks of treatment)
measure: Rate of HBV DNA <20IU/mL
timeFrame: week 72 (24 weeks after 48 weeks of treatment)
measure: Rate of HBsAg seroconversion
timeFrame: week 72 (24 weeks after 48 weeks of treatment)
measure: Percentage of patients reaching a ≥ 1log10 decline of quantitative HBsAg
timeFrame: week 72 (24 weeks after 48 weeks of treatment)
measure: Decline of quantitative HBsAg from baseline
timeFrame: week 72 (24 weeks after 48 weeks of treatment
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital, Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The Second Affiliated Hospital, Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Ditan Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fuzhou Municipal Infectious Disease Hospital
state: Fujian
city: Guangzhou
country: China
facility: Zhongshan No.2 People's Hospital, Zhongshan, Guangdong
state: Guangdong
city: Shenzhen
country: China
facility: The third People's Hospital of Shenzhen
state: Guangdong
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Suzhou
country: China
facility: Fifth People's Hospital of Suzhou
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical College
state: Jiangsu
city: Shenyang
country: China
facility: Shenyang Municipal Infectious Disease Hospital
state: Liaoning
city: Jinan
country: China
facility: Shandong Provincial Hospital of Shandong University
state: Shandong
city: Xi'an
country: China
facility: The First Affiliated Hospital Medical School of Xi'an Jiaotong University
state: Shanxi
city: Luzhou
country: China
facility: The Affiliated Hospital of Luzhou Medical College
state: Sichuan
city: Sichuan
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
city: Ningbo
country: China
facility: The Second Hospital of Yinzhou of Ningbo
state: Zhejiang
city: Rui'an
country: China
facility: Rui'an People's Hospital
state: Zhejiang
Study officials:
affiliation: Huashan Hospital
name: Wenhong Zhang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: