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

Sun Yat-sen University

Status and phase: Completed; Phase 4

Conditions: Hepatitis B, Chronic

Treatments: Drug: Telbivudine 600mg; Drug: Tenofovir disoproxil fumarate 300mg

Study type: Interventional

Funder types: Other

Identifiers

NCT03468907

Safety of anti-viral agents

Details and patient eligibility

About

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.

Full 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.

Enrollment: 111 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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111 participants in 3 patient groups

Early cessation

Experimental group

Description:

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.

Treatment:

Drug: Tenofovir disoproxil fumarate 300mg

Drug: Telbivudine 600mg

Late cessation

Experimental group

Description:

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.

Treatment:

Drug: Tenofovir disoproxil fumarate 300mg

Drug: Telbivudine 600mg

Control

No Intervention group

Description:

Eligible patients who refused antiviral therapy but consented to the study were assigned to the control arm.