The Safety of Anti-viral Therapy in Preventing HBV MTCT in Pregnant Women After Discontinuation

Hepatitis B, Chronic Clinical Trial

Official title:

The Safety of Anti-viral Therapy in Preventing Mother-to-child Transmission of Hepatitis B Virus in Pregnant Women After Discontinuation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03468907
• Other study ID #: Safety of anti-viral agents
• Status: Completed
• Phase: Phase 4
• Start date: June 1, 2015
• Est. completion date: December 31, 2017

Study information

• Verified date: August 2018
• Source: Third Affiliated Hospital, Sun Yat-Sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: December 31, 2017
• Est. primary completion date: December 31, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• Telbivudine 600mg
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
• Tenofovir disoproxil fumarate 300mg
Pregnant mothers who opted for antiviral therapy would start on oral TDF 300 mg daily between gestational weeks 24 and 28.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Third Affiliated Hospital, Sun Yat-Sen University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Postpartum flare incidence	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.	From baseline to postpartum 12 months.
Secondary	Time of flare onset	Time-to-event measures. Time of the onset of postpartum liver damage.	Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
Secondary	Proportion of severe flares	As per protocol, ALT flares (>5 times baseline level or >10 times ULN) were considered severe adverse events (SAEs).	Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
Secondary	Peak ALT during flare	Peak ALT during postpartum flare.	Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
Secondary	The rate of perinatal transmission	Perinatal transmission was established by detectable HBV DNA and HBsAg levels in the peripheral blood of infants at 7 months.	7 months after birth.
Secondary	HBV kinetics in patients	Changes of HBV viral load in patients treated and not treated with antiviral agents.	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.
Secondary	The liver function normalization rate	Normal liver function was defined as the value of ALT level lower 40U/L.	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.
Secondary	Maternal HBsAg loss/seroconversion rate	Measurement of the proportion of maternal hepatitis B surface antigen loss and seroconversion.	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.
Secondary	Incidence of perinatal and partum complications	Perinatal and partum complications included hypertensive disorders in pregnancy, gestational diabetes mellitus, fetal growth retardation, premature delivery, premature rupture of membrane, and postpartum hemorrhage.	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.
Secondary	Birth height	Measurement of infants' height at the time of delivery.	At the time of delivery.
Secondary	Birth weight	Measurement of infants' weight at the time of delivery.	At the time of delivery.
Secondary	Neonate apgar score at 1 minute	Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.	At 1 minute after birth.
Secondary	Neonate apgar score at 5 minutes	Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.	At 5 minutes after birth.
Secondary	Incidence of deformity	The incidence of baby deformity was recorded during the postpartum follow-up period.	At the time of delivery; at 1, 7, 12 month postpartum.
Secondary	Breastfeeding rate	Breast feeding status was assessed in all infants during the postpartum follow-up period.	At birth, at 1 and 7 month follow-up.