Clinical trial NCT03181607: Efficacy and Adverse Effects of Nucleoside Analogues (TDF/LDT) in Preventing Mother-to-child Transmission of HBV
Official title: The 3rd Affiliated Hospital, Guangzhou Medical University
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Hepatitis b
Women
Lead sponsor: The Third Affiliated Hospital of Guangzhou Medical University
Sponsor class: OTHER
First posted: 2017-06-09
Enrollment: 300
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Child-bearing age women with chronic HBV infection, who already become pregnant or plan to become pregnant recently,and visit in our hospital, are enrolled.

Brief summary: Mother-to-Child-Transmission (MTCT) of HBV is the most important route in high endemic countries. Although active-passive immune prophylaxis is generally administrated to infants delivered by HBsAg positive women, there are a lot of people infected with HBV in China. High HBV DNA load (\>10\^5IU/ml) is the vital cause of MTCT. So some researchers used TDF （tenofovir） or LDT（telbivudine） to treat patients with high HBV DNA load during middle, late pregnancy, in order to decrease MTCT. As a result, some data about it were gradually reported in late years. Recently, American Association for the Study of Liver Diseases, European Association for the Study of Liver Diseases and China guidelines for CHB (chronic hepatitis B) suggest that pregnant women with high HBV DNA load be treated with TDF or LDT at 24-28 weeks of gestation to lower MTCT of HBV.

Although TDF or LDT is classified as pregnancy B drugs by FDA, and many studies report that MTCT rate of HBV decreases after women with high HBV DNA load are administrated with TDF or LDT at 24-28 weeks of gestation, a few birth defects are reported. Furthermore, the long-effect of TDF or LDT on infants remains unclear thoroughly.

Some CHB women had severe liver dysfunction before pregnancy or during pregnancy, and routine liver protection therapy could not effect. Some of them could develop into liver failure, fibrosis, cirrhosis, and even died. Moreover, severe liver dysfunction often leads to adverse effects to pregnant women and fetuses, such as pregnancy failure, lower weight, premature birth, etc. As a result, these women have to accept TDF or LDT before pregnancy, or during early pregnancy. So the long-effect of TDF or LDT on infants needs thoroughly investigating.

Taken together, the investigators will enroll women with chronic HBV infection and evaluate their state of illness. Then the investigators treat participants with TDF or LDT or routine liver protection therapy, and follow up the participants for a long period. The investigators' objectives are as follows:

A, To clarify efficacy and adverse effects of TDF/LDT in preventing MTCT between immune-tolerant and immune-active CHB patients.

B, To clarify efficacy and adverse effects of TDF/LDT in preventing MTCT during different trimesters of pregnancy.

C, To compare MTCT rate between patients received TDF/LDT therapy and patients without TDF/LDT therapy.

D, To compare MTCT rate and adverse effects between LDT and TDF.


Eligibility criteria: Inclusion Criteria:

* Age of 20-40 years.
* The history of HBV infection ≥6 months.
* Positive for HBsAg.
* For immune-tolerant patients, HBV DNA load of ≥ 10\^6IU/ml at 24-28 weeks of gestation.
* For patients already administrated with nucleoside analogues (NA) treatment, the therapy could be not discontinued and TDF or LDT should be used to treat these patients.
* For patients never administrated with NA treatment, ALT ≥2 times of the upper limit of normal (ULN), HBV DNA load of ≥ 10\^4IU/ml (positive for HBeAg) or HBV DNA load of ≥ 10\^3IU/ml (negative for HBeAg), traditional protecting liver and reducing enzyme treatment was failed.
* The good compliance of patients.

Exclusion Criteria:

* Patients with antibodies against HIV, HCV, HDV, or other forms of chronic liver disease.
* Evidence of hepatocellular carcinoma, decompensated liver disease, auto-immune hepatitis, or significant renal, cardiovascular, respiratory or neurological comorbidity.
* Concurrent treatment with nephrotoxic drugs, glucocorticoids, cytotoxic drugs, nonsteroidal anti-inflammatory drugs, or immune modulators.
* Ultra-sonographic evidence of fetal deformity, abnormal fetal development or placental abnormality.
* Clinical signs of threatened miscarriage.
* History of complication of pregnancy.
* Presence of chronic HBV infection in the biologic father.

Primary outcomes:
measure: The proportion of hepatitis B infections in the infants at 1 year of age
timeFrame: Between 7-12 months after birth
Secondary outcomes:
measure: The proportion of birth defects in the infants at 1 month age
timeFrame: From birth to 1 month age
measure: Growth parameters of the infants
timeFrame: From birth to 5 years age
measure: HBV DNA quantification of mothers
timeFrame: From time of the inclusion to 5 years.
measure: ALT levels of mothers
timeFrame: From time of the inclusion to 5 years.
measure: HBeAg conversion rate of mothers
timeFrame: From time of the inclusion to 5 years.
Other outcomes:
Locations:
city: Guanzhou
country: China
facility: The 3rd Affiliated Hospital, Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: The 3rd Affiliated Hospital, Guangzhou Medical University
name: Xingfei Pan, Dr.
role: STUDY_DIRECTOR
References: