Clinical trial NCT01726439: Effectiveness of Nucleos(t)Ide Analogs (NUC) Therapy Among Naive CHB Patients in China
Official title: A 5-year Prospective and Observational Study to Evaluate the Effectiveness of Nucleos(t)Ide Analogs (NUC) Therapy Among Chronic Hepatitis B (CHB) Patients Naive to NUC in Real World Practice at Hospitals in Tier 2 Cities in China (the EVOLVE Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Hepatitis B
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-11-15
Enrollment: 3434
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hospitals in Chinese tier 2 cities. The definition of these hospitals is the following:

* Hospitals where 300 or more CHB patients are treated monthly
* Hospitals where PCR can be performed in the hospital's laboratory to measure HBV DNA serum levels

Brief summary: To compare the effectiveness, in a real world practice setting in tier 2 cities of China, of Entecavir (ETV) monotherapy and Lamivudine (LAM) based therapies (including LAM monotherapy, de novo LAM + Adefovir \[ADV\] combination, and early add-on of ADV) among chronic hepatitis B (CHB) patients who are naive to NUC at enrollment to this study

Detailed description: Sampling Method: Consecutive patient sampling

Biospecimen Retention: Blood samples for HBV viral load testing along the treatment period of this study

Eligibility criteria: Inclusion Criteria:

* CHB patients, or CHB patients with compensated cirrhosis, as defined by the current Chinese guidelines
* Male or female
* ≥ 18 years of age
* Either Hepatitis B e antigen (HBeAg) positive or negative
* Naïve to NUC (defined as no previous exposure to NUC treatment as based on patient self-report)
* Has compensated liver disease
* Patients with compensated cirrhosis
* Patients who consent to participate in this study
* Local residents with medical reimbursement coverage preferred

Exclusion Criteria:

* Co-infected with hepatitis C virus (HCV)
* CHB patients with decompensated cirrhosis, liver failure, hepatocellular carcinoma, or any other types of malignancy at the screening phase
* CHB patients who are being treated by interferon therapy within 6 months immediately prior to the screening phase of this study
* CHB patients with a confirmed pregnancy

Primary outcomes:
measure: Proportion of patients who achieve virology response (defined as HBV DNA < 300 copies/mL) by ETV monotherapy in comparison with LAM-based therapy
timeFrame: 48 weeks after initial NUC antiviral therapy
Secondary outcomes:
measure: Mean HBV DNA reductions after 48 weeks of treatment from baseline for ETV and LAM-based therapy patients (stratifying by the 3 LAM-based subgroups)
timeFrame: Baseline (Day 1) and 48 weeks
measure: Proportion of patients who achieve virology response by ETV in comparison with LAM-based therapy after 24 weeks and 96 weeks of treatment (stratifying by the 3 LAM based subgroups)
timeFrame: 24 weeks and 96 weeks
measure: Proportion of patients who modify their initial treatment options to manage suboptimal response or resistance after 24 weeks, 48 weeks, and 96 weeks of treatment among all treatment options
timeFrame: 24 weeks, 48 weeks and 96 weeks
measure: Proportion of patients who achieve virology response among other treatment options, including ADV, LdT, and combinations of NUCs, after 24 weeks, 48 weeks, 72 weeks, 96 weeks, 144 weeks, 192 weeks and 240 weeks of treatment
timeFrame: 24 weeks, 48 weeks, 72 weeks, 96 weeks, 144 weeks, 192 weeks and 240 weeks
measure: Cumulative incidence of patients who develop viral breakthrough and/or genotypic resistance
timeFrame: 24 weeks, 48 weeks, 72 weeks, 96 weeks, 144 weeks, 192 weeks and 240 weeks
measure: Cumulative incidence of clinical outcome (eg, HCC, death, decompensated cirrhosis) in ETV arm versus LAM-based and other treatment arms
timeFrame: 48 weeks, 96 weeks, 144 weeks, 192 weeks and 240 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Chongqing
country: China
facility: Local Institution
state: Chongqing
city: Chongqing
country: China
facility: Local Institution
state: Chongqing
city: Fuzhou
country: China
facility: Local Institution
state: Fujian
city: Quanzhou
country: China
facility: Local Institution
state: Fujian
city: Xiamen
country: China
facility: Local Institution
state: Fujian
city: Foshan
country: China
facility: Local Institution
state: Guangdong
city: Shenzhen
country: China
facility: Local Institution
state: Guangdong
city: Nanning
country: China
facility: Local Institution
state: Guangxi
city: Guiyang
country: China
facility: Local institution
state: Guizhou
city: Guiyang
country: China
facility: Local Institution
state: Guizhou
city: Haikou
country: China
facility: Local Institution
state: Hainan
city: Baoding
country: China
facility: Local Institution
state: Hebei
city: Shijiazhuang
country: China
facility: Local Institution
state: Hebei
city: Daqing
country: China
facility: Local Institution
state: Heilongjiang
city: Haerbin
country: China
facility: Local Institution
state: Heilongjiang
city: Zhengzhou
country: China
facility: Local Institution
state: Henan
city: Zhengzhou
country: China
facility: Local Institution
state: Henan
city: Shiyan
country: China
facility: Local Institution
state: Hubei
city: Wuhan
country: China
facility: Local Institution
state: Hubei
city: Wuhan
country: China
facility: Local Institution
state: Hubei
city: Changsha
country: China
facility: Local Institution
state: Hunan
city: Changsha
country: China
facility: Local Institution
state: Hunan
city: Changsha
country: China
facility: Local Institution
state: Hunan
city: Erdos
country: China
facility: Local Institution
state: Inner Mongolia
city: Changshu
country: China
facility: Local Institution
state: Jiangsu
city: Changzhou
country: China
facility: Local Institution
state: Jiangsu
city: Nanjing
country: China
facility: Local Institution
state: Jiangsu
city: Suzhou
country: China
facility: Local Institution
state: Jiangsu
city: Nangchang
country: China
facility: Local Institution
state: Jiangxi
city: Changchun
country: China
facility: Local Institution
state: Jilin
city: Yanji
country: China
facility: Local institution
state: Jilin
city: Dalian
country: China
facility: Local Institution
state: Liaoning
city: Fushun
country: China
facility: Local Instution
state: Liaoning
city: Shengyang
country: China
facility: Local Institution
state: Liaoning
city: Shenyang
country: China
facility: Local Institution
state: Liaoning
city: Yinchuan
country: China
facility: Local Institution
state: Ningxia
city: Jinan
country: China
facility: Local Institution
state: Shandong
city: Qingdao
country: China
facility: Local Institution
state: Shandong
city: Yantai
country: China
facility: Local Institution
state: Shandong
city: Taiyuan
country: China
facility: Local Institution
state: Shanxi
city: Taiyuan
country: China
facility: Local Institution
state: Shanxi
city: Xi'an
country: China
facility: Local Institution
state: Shanxi
city: Xi'an
country: China
facility: Local Institution
state: Shanxi
city: Chengdu
country: China
facility: Local Institution
state: Sichuan
city: Chengdu
country: China
facility: Local Institution
state: Sichuan
city: Tianjin
country: China
facility: Local Institution
state: Tianjin
city: Urumqi
country: China
facility: Local Institution
state: Xinjiang
city: Wulumuqi
country: China
facility: Local Institution
state: Xinjiang
city: Wulumuqi
country: China
facility: Local Institution
state: Xinjiang
city: Hangzhou
country: China
facility: Local institution
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution
state: Zhejiang
city: Jinghua
country: China
facility: Local Institution
state: Zhejiang
city: Ningbo
country: China
facility: Local Institution
state: Zhejiang
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Jia J, Shang J, Tang H, Jiang J, Ning Q, Dou X, Zhang S, Zhang M, Han T, Tan D, Zhou X, Chen G, Sheng J, Su Z, Chen H, Dai E, Ye Y, Guo Y, Shen Y, Yuan J, Wei Z, Zhu S; EVOLVE Study Group. Long-term outcomes in Chinese patients with chronic hepatitis B receiving nucleoside/nucleotide analogue therapy in real-world clinical practice: 5-year results from the EVOLVE study. Antivir Ther. 2020;25(6):293-304. doi: 10.3851/IMP3372.
citation: Jia J, Tang H, Ning Q, Jiang J, Dou X, Zhang M, Zhang S, Shang J, Lu W, Ye Y, Wang X, Li M, Liu J, Bo Q, Tan W; EVOLVE Study Group. Real-world evidence for nucleoside/nucleotide analogues in a 5-year multicentre study of antiviral-naive chronic hepatitis B patients in China: 52-week results. Antivir Ther. 2018;23(3):201-209. doi: 10.3851/IMP3205.