Clinical trial NCT04724785: Real World Study About Anti-viral Regimen Adjustment on Achieving Complete Response in CHB Patients
Official title: Real World Study on the Effect of HBV-DNA High-precision Detection Based Anti-viral Regimen Adjustment on Achieving Complete Virologic Response in Patients With Chronic Hepatitis B.(REACH)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sustained Virologic Response
Hepatitis B, Chronic
Lead sponsor: The Second Affiliated Hospital of Chongqing Medical University
Sponsor class: OTHER
First posted: 2021-01-26
Enrollment: 10000
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The research subjects were patients with CHB (chronic hepatitis B) receiving ETV or second-line NA(LAM/ADV/LdT) who were admitted to The Second Affiliated Hospital of Chongqing Medical University and other centers.

Brief summary: In the treatment of chronic hepatitis B (CHB), viral suppression is closely related to disease progression, and the lower the viral load, the lower the risk of progression to cirrhosis and hepatocellular carcinoma (HCC). In addition, a considerable number of patients in China are still using non-first-line antiviral therapy, such as adefovir dipivoxil, lamivudine, and telbivudine (ADV/LAM/LdT). About 25% of patients who received entecavir(ETV) treatment for more than half a year and confirmed that their DNA had turned negative by non-high-precision detection methods still had low viremia (LLV,DNA\>20 IU/ml,IU=international unit), and LLV patients were twice as likely to develop HCC as patients with complete viral response.Patients who have received ETV or second-line NA(LAM/ADV/LdT) treatment for more than half a year to 1 year and confirmed HBV-DNA\>10IU/ml by high-precision detection method are recommended to adjust the treatment plan in order to reduce the DNA load below 10IU/ml as soon as possible. It is up to the doctor, in consultation with the patient, to decide whether or not to make the adjustment.

Detailed description: In our hospital, about 150 patients are screened for HBV-DNA every day. Therefore, 54 million patients will be tested for HBV-DNA within one year, of which 30% are estimated to be HBV-DNA ≥10 IU. These patients will be informed to the Department of Infectious Diseases of the Second Affiliated Hospital of Chongqing Medical University for follow-up, and will be randomly divided into three groups according to 1:1. Patients in all three groups will be educated about hepatitis B virus infection and antiviral treatment, and the treatment regimen will be adjusted according to whether their HBV DNA is ≥10 IU/ml or not. Patients in group 1: patients with persistant low level HBV DNA (\<10 IU/ml). Patients in group 2: HBV-DNA≥10 IU/ml, receiving HBV-related education and being advised by the doctor to change or to add another NA. Patients in group 2: patients with persistant HBV DNA (\>10 IU/ml) but refuse to change the regimen. Patients in group 3: patients with persistant HBV DNA (\>10 IU/ml) and agree to change the regimen. Educational methods include videos, including an introduction to hepatitis B virus (disease profile, infection, outcome, HBV infection, vertical transmission and other risk factors) for 5 minutes, brochures with relevant information and consultations with physicians and nurses.

All patients with chronic hepatitis B(CHB) receiving ETV or second-line NA(LAM/ADV/LdT) treatment for more than six months to one year will receive HBV-DNA detection, and patients with HBV-DNA≥10 IU/ml will be informed and recommended to adjust the treatment regimen so that the actual prevalence of HBV-DNA load \< 10 IU/ml in Chongqing HBV cohort could be obtained . The investigators estimated that 30% of the patients had HBV-DNA≥ 10 IU/ml, so there were about 16,200 patients had HBV-DNA≥ 10 IU/ml among 54,000 patients a year. These patients will be diagnosed with LLV and will undergo a treatment regimen adjustment, with a recommendation to switch to or use a different type of nucleos(t)ide analogue (NA) for anti-viral treatment.

Eligibility criteria: Inclusion Criteria:

* any patients treated with ETV\\LAM\\ADF\\LDT\\TDF\\TAF.【ADV=adefovir dipivoxil, LAM=lamivudine, and LdT=telbivudine , TAF =Tenofovir alafenamide Fumarate, ETV=Entecavir and TDF=Tenofovir disoproxil fumarate 】

Exclusion Criteria:

* with a expected life span \<48 weeks

Primary outcomes:
measure: The proportion of patients who received a complete virologic response (HBV DNA<10IU/ml) at 24 weeks after therapy adjustment.
timeFrame: 24 weeks
Secondary outcomes:
measure: The proportion of patients with complete virologic response (HBV DNA<10IU/ml) at 12 weeks, 48 weeks and 96 weeks after therapy adjustment.
timeFrame: 12 weeks, 48 weeks ,96 weeks
measure: he proportion of patients with normal Alanine transaminase（ALT） at baseline and at each follow-up time point
timeFrame: baseline,12 weeks,48 weeks,96 weeks
measure: Changes of estimated glomerularfiltrationratee(GFR) compared with baseline at each follow-up time point.
timeFrame: baseline,12 weeks,48 weeks,96 weeks
measure: Changes of serum creatinine(SCr）compared with baseline at each follow-up time point.
timeFrame: baseline,12 weeks,48 weeks,96 weeks
measure: Changes of bone mass density（BMD) compared with baseline at each follow-up time point.
timeFrame: baseline,12 weeks,48 weeks,96 weeks
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The second affiliated Hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: The Second Affiliated Hospital of Chongqing Medical University
name: DACHUAN CAI, PhD
role: PRINCIPAL_INVESTIGATOR
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