Comparison of TAF and TDF in Preventing Mother-to-Child Transmission of HBV in Pregnancies With High Viral Loads

Official title

A Multicenter, Prospective, Open-label, Non-inferiority Randomized Controlled Study on the Efficacy of Tenofovir Alafenamide Fumarate vs. Tenofovir Disoproxil Fumarate in Preventing Mother-to-Child Transmission of Hepatitis B Virus in Pregnant Women With High Viral Loads

Overview

The main objective of this study is to compare the mother-to-infant transmission rates of hepatitis B between pregnant women receiving treatment with tenofovir alafenamide and those receiving treatment with tenofovir disoproxil fumarate, after administering the hepatitis B vaccine and hepatitis B immunoglobulin to their infants at birth. Investigators define the mother-to-infant transmission rate of hepatitis B as the proportion of infants who are HBsAg positive and have serum HBV DNA \>20 IU/mL at 28 weeks of age among all live births in the experimental group. Additionally, this study will also compare the incidence of congenital defects/malformations in infants born to mothers treated with tenofovir alafenamide and tenofovir disoproxil fumarate during the perinatal period to assess drug safety.

Detailed description

see summary

Interventions

• Drug TAF group
  Pregnant women will start TAF treatment (25 mg tablet taken orally once daily) from 28 weeks of gestation until delivery. After that, they will be randomly assigned to two subgroups among postpartum mothers without treatment indications: one subgroup will stop treatment, while the other subgroup will continue with an additional 12 weeks of TAF treatment. The mothers and their infants will be followed up at 28 weeks postpartum. Infants will receive the hepatitis B vaccine and HBIG within 12 hours
• Drug TDF group
  The mother will start receiving TDF treatment (300 mg tablet taken orally once daily) at 28 weeks of pregnancy until delivery. After that, mothers without treatment indications will be randomly assigned to two subgroups: one subgroup will stop treatment, while the other subgroup will receive an additional 12 weeks of TDF treatment. Infants will be vaccinated with the hepatitis B vaccine and HBIG within 12 hours after birth, as well as receive booster doses of the hepatitis B vaccine at 4 weeks a

Primary outcome measures

• The mother-to-child transmission rate of HBV [Time frame: 28 weeks]

Secondary outcome measures (10)

• Congenital defects/malformations in infants [Time frame: 28 weeks]
• The percentage of mothers in each group of pregnant women with HBV DNA below 200,000 IU/mL [Time frame: 12 weeks]
• The percentage of mothers who experienced HBeAg/HBsAg clearance or seroconversion [Time frame: 36 weeks]
• ALT levels during or after TDF/TAF treatment [Time frame: 36 weeks]
• Renal function parameters of pregnant women [Time frame: 36 weeks]
• Adverse events (including obstetric complications and laboratory abnormalities) [Time frame: 36 weeks]
• Proportion of two groups that discontinued treatment due to adverse events [Time frame: 36 weeks]
• Health-related quality of life (HRQoL) indicators of pregnant women [Time frame: 36 weeks]
• Health-related quality of life (HRQoL) indicators of pregnant women [Time frame: 36 weeks]
• Health-related quality of life (HRQoL) indicators of pregnant women [Time frame: 36 weeks]

Eligibility criteria

Inclusion criteria

• Pregnant women aged between 20 and 40 years old
• Pregnancy duration between 20 to 28 weeks (screening for eligible patients can start from the 20th week of gestation)
• Clinically diagnosed with compensated chronic hepatitis B, HBsAg positive for more than 6 months, with clinical history, signs, and test results consistent with compensated chronic hepatitis B
• HBsAg and HBeAg positive in maternal serum during screening
• PCR testing shows maternal serum HBV DNA levels exceeding 200,000 IU/mL
• Subjects voluntarily agree to undergo treatment according to the study design's drug treatment plan and all other research requirements, and patients consent to strictly avoid pregnancy within 28 weeks postpartum
• Patients and their husbands (the biological parents of the child) understand the risks and voluntarily participate in the study. The mother must participate voluntarily and sign a written informed consent document before participating in the study.

Exclusion criteria

• Creatinine clearance < 100 mL/min (calculated using the Cockcroft-Gault method based on serum creatinine and ideal body weight), or hypophosphatemia (below normal range).
• History of adverse renal reactions induced by Adefovir or history of Adefovir resistance.
• Meeting one of the following criteria: hemoglobin < 80 g/L, neutrophil count < 1000/μL, ALT > 5 times the upper limit of normal, total bilirubin > 20 mg/L, albumin < 25 g/L, abnormal levels of creatinine or urea nitrogen.
• Pregnant women with a history of miscarriage, history of giving birth to a child with congenital malformations, or history of fetal infection with hepatitis B virus.
• The biological father of the current pregnancy has chronic hepatitis B.
• The investigator assesses that the subject has significant kidney, cardiovascular, pulmonary, or neurological diseases that affect their participation in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

China · 10 centers

• Guangzhou Eighth People's Hospital, Guangzhou Medical University — Guangzhou
• Guangzhou Women and Children's Medical Center — Guangzhou
• The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou — Guangzhou
• The Third Affiliated Hospital of Guangzhou Medical University — Guangzhou
• Shenzhen Baoan Women's and Children's Hospital — Shenzhen
• Shijiazhuang Maternity & Child Healthcare Hospital — Shijiazhuang
• The Fifth Hospital of Shijiazhuang — Shijiazhuang
• Xiangya Hospital, Central South University — Changsha
• … and 2 more centers

Identifiers

NCT: NCT06947356 · US-CN-P818

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗