Clinical trial NCT03468907: The Safety of Anti-viral Therapy in Preventing HBV MTCT in Pregnant Women After Discontinuation
Official title: The Safety of Anti-viral Therapy in Preventing Mother-to-child Transmission of Hepatitis B Virus in Pregnant Women After Discontinuation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis B, Chronic
Keywords: hepatitis B virus
exacerbation
antiviral agents
pregnancy
flare
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2018-03-19
Enrollment: 111
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pregnant mothers who opt for antiviral therapy will start on oral LDT 600 mg or TDF 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28. Antiviral therapy will be discontinued in intrapartum or at postpartum 6 weeks.
Primary purpose: PREVENTION

Brief summary: Mother-to-child transmission (MTCT) is the most common mode of perpetuating chronic hepatitis B virus (HBV) infection in endemic countries. Many studies have demonstrated antepartum anti-viral therapy (AVT) is a advisable option to reduce mother-to-child transmission and the risk of vaccination breakthrough in infants who received passive-active immunoprophylaxis. However, several controversies over antiviral treatment have not been resolved, that is, optimal duration, effect of postpartum therapy, and risk of postpartum alanine aminotransferase (ALT) flare after withdrawal. Will the risk of postpartum hepatitis flares increase after short-term AVT in late pregnancy for maternal HBV infection is discontinued? Is there any correlation between postpartum hepatitis flares and withdrawal time? Will the proportion of postpartum flares be reduced if extending the duration of AVT after delivery? There is an urgent need in this area. This study mainly investigated the safety of antiviral therapy in preventing HBV mother-to-child transmission in pregnant women after discontinuation.

Detailed description: Between June 2015 and December 2017, 111 mothers were enrolled during their visit to the Department of Gynecology and Obstetrics or the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-Sen University in Guangzhou, Guangdong province, China. Pregnant women fulfilling the inclusion and exclusion criteria were offered participation in the study. All pregnant women who opted for AVT need to sign a consent form and started on oral telbivudine (LDT) 600 mg or tenofovir disoproxil fumarate (TDF) 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28. Serum levels of HBV DNA, HBsAg, HBsAb, HBeAg, HBeAb, liver function tests, haematology and renal biochemistry were measured at baseline(i.e. at screening), every 4 weeks after treatment begins, at the time of delivery, and at 1, 2, 3, 6, 12 month postpartum. After delivery, treatment with LDT or TDF was immediately withdrew to the patients with an intention of breastfeeding, while the other patients, without desire of breastfeeding, would subsequently extend antiviral treatment duration to postpartum 6 weeks. All infants were vaccinated with genetically engineered HBV vaccine 20 ug according to a standard vaccination regimen (i.e. within 12h of birth, at week 4 and at week 24) and 200 IU doses of hepatitis B immunoglobulin immediately (within 2h) after birth and at day 15. The infant's HBV serologic status and HBV DNA were tested at birth (before immunization) and again at 7 months. The investigators discussed the postpartum liver function after withdrawal and evaluated the impact of extending the postpartum duration of AVT administered for the prevention of perinatal transmission.

Eligibility criteria: Inclusion Criteria:

* Gestational age between 24 and 28 weeks
* Detectable serum HBsAg at the Screening visit and at least 6 months prior
* Serum HBV DNA level \>1,000,000 IU/mL at Screening visit
* Alanine aminotransferase (ALT) below the upper limit of normal (ULN; 40 IU/mL)

Exclusion Criteria:

* Patient is co-infected with hepatitis A virus, hepatitis C virus, hepatitis delta virus, hepatitis E virus or HIV.
* Patient has a history of antiviral treatment or concurrent treatment with immunomodulators, cytotoxic drugs, or steroids.
* Patient has clinical signs of threatened miscarriage in early pregnancy.
* Patient has evidence of hepatocellular carcinoma or cirrhosis.
* Patient has evidence of fetal deformity by 3-dimensional ultrasound examination.
* Patient has a husband infected with HBV.

Primary outcomes:
measure: Postpartum flare incidence
timeFrame: From baseline to postpartum 12 months.
Secondary outcomes:
measure: Time of flare onset
timeFrame: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
measure: Proportion of severe flares
timeFrame: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
measure: Peak ALT during flare
timeFrame: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
measure: The rate of perinatal transmission
timeFrame: 7 months after birth.
measure: HBV kinetics in patients
timeFrame: Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
measure: The liver function normalization rate
timeFrame: Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
measure: Maternal HBsAg loss/seroconversion rate
timeFrame: Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
measure: Incidence of perinatal and partum complications
timeFrame: Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
measure: Birth height
timeFrame: At the time of delivery.
measure: Birth weight
timeFrame: At the time of delivery.
measure: Neonate apgar score at 1 minute
timeFrame: At 1 minute after birth.
measure: Neonate apgar score at 5 minutes
timeFrame: At 5 minutes after birth.
measure: Incidence of deformity
timeFrame: At the time of delivery; at 1, 7, 12 month postpartum.
measure: Breastfeeding rate
timeFrame: At birth, at 1 and 7 month follow-up.
Other outcomes:
Locations:
Study officials:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Zhi-liang Gao, PhD
role: STUDY_CHAIR
References: