The Safety of Anti-viral Therapy in Preventing Mother-to-child Transmission of Hepatitis B Virus in Pregnant Women After Discontinuation
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 111
- Primary Endpoint
- Postpartum flare incidence
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Masking Description
The care provider, participant, investigator and outcomes assessor all konw the process.
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Early cessation
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg or TDF 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28. Antiviral therapy was discontinued in intrapartum.
Intervention: Telbivudine 600mg (Drug)
Early cessation
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg or TDF 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28. Antiviral therapy was discontinued in intrapartum.
Intervention: Tenofovir disoproxil fumarate 300mg (Drug)
Late cessation
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg or TDF 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28. After delivery, mothers ceased antiviral treatment at postpartum 6 weeks.
Intervention: Telbivudine 600mg (Drug)
Late cessation
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg or TDF 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28. After delivery, mothers ceased antiviral treatment at postpartum 6 weeks.
Intervention: Tenofovir disoproxil fumarate 300mg (Drug)
Outcomes
Primary Outcomes
Postpartum flare incidence
Time Frame: From baseline to postpartum 12 months.
Time-to-event measures. Postpartum flare was defined as an alanine aminotransferase (ALT) rise to three times baseline level or five times ULN (40U/L) within 12 months post-delivery. Maternal would be recorded if postpartum flare occured. At the end of postpartum 12-month follow-up period, postpartum flare incidence was measured.
Secondary Outcomes
- Peak ALT during flare(Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.)
- The rate of perinatal transmission(7 months after birth.)
- HBV kinetics in patients(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.)
- The liver function normalization rate(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.)
- Neonate apgar score at 1 minute(At 1 minute after birth.)
- Neonate apgar score at 5 minutes(At 5 minutes after birth.)
- Incidence of deformity(At the time of delivery; at 1, 7, 12 month postpartum.)
- Maternal HBsAg loss/seroconversion rate(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.)
- Incidence of perinatal and partum complications(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.)
- Breastfeeding rate(At birth, at 1 and 7 month follow-up.)
- Time of flare onset(Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.)
- Birth height(At the time of delivery.)
- Proportion of severe flares(Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.)
- Birth weight(At the time of delivery.)
Investigators
Chao-Shuang Lin
Professor
Third Affiliated Hospital, Sun Yat-Sen University