Efficacy and Adverse Effects of Nucleoside Analogues (TDF/LDT) in Preventing Mother-to-child Transmission of HBV

Chronic Hepatitis b Clinical Trial

Official title:

The 3rd Affiliated Hospital, Guangzhou Medical University

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03181607
• Other study ID #: [2017] No.157
• Status: Enrolling by invitation
• Start date: January 1, 2017
• Est. completion date: December 31, 2021

Study information

• Verified date: November 2021
• Source: The Third Affiliated Hospital of Guangzhou Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 300
• Est. completion date: December 31, 2021
• Est. primary completion date: May 26, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis b
• Hepatitis B
• Hepatitis B, Chronic
• Women

Locations

Country	Name	City	State
China	The 3rd Affiliated Hospital, Guangzhou Medical University	Guanzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Xingfei Pan

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of hepatitis B infections in the infants at 1 year of age	Testing for HBsAg in the infants between 7 and 12 months of age	Between 7-12 months after birth
Secondary	The proportion of birth defects in the infants at 1 month age	Measuring the number of infants with congenital abnormality	From birth to 1 month age
Secondary	Growth parameters of the infants	The infants'physical development status (head circumference, weight, and height) is measured and analyzed, respectively. Denver Developmental Screening Test is also analyzed.	From birth to 5 years age
Secondary	HBV DNA quantification of mothers	HBV DNA quantification is detected at 24-28 weeks of gestation, at birth, every 6 month after postpartum.	From time of the inclusion to 5 years.
Secondary	ALT levels of mothers	ALT levels are measured every month during pregnancy and the first 3 months postpartum, and every 6 month from the fourth month of postpartum.	From time of the inclusion to 5 years.
Secondary	HBeAg conversion rate of mothers	HBeAg quantification is measured every 6 month.	From time of the inclusion to 5 years.