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Completed

NCT Number: NCT03468907

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

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.

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Key information

Conditions

Hepatitis B, Chronic Blood-Borne Infections Chronic Disease Communicable Diseases DNA Virus Infections Digestive System Diseases Disease Attributes Hepadnaviridae Infections Hepatitis Hepatitis B Hepatitis, Chronic Hepatitis, Viral, Human Infections Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Virus Diseases

Age range

18 year–45 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Telbivudine 600mg

Drug

Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.

Other names: Sebivo

Tenofovir disoproxil fumarate 300mg

Drug

Pregnant mothers who opted for antiviral therapy would start on oral TDF 300 mg daily between gestational weeks 24 and 28.

Other names: Viread

Primary outcomes

  1. 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

  1. Time of flare onset

    Time frame: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.

    Time-to-event measures. Time of the onset of postpartum liver damage.

  2. Proportion of severe flares

    Time frame: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.

    As per protocol, ALT flares (>5 times baseline level or >10 times ULN) were considered severe adverse events (SAEs).

  3. Peak ALT during flare

    Time frame: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.

    Peak ALT during postpartum flare.

  4. The rate of perinatal transmission

    Time frame: 7 months after birth.

    Perinatal transmission was established by detectable HBV DNA and HBsAg levels in the peripheral blood of infants at 7 months.

  5. HBV kinetics in patients

    Time frame: 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.

    Changes of HBV viral load in patients treated and not treated with antiviral agents.

  6. The liver function normalization rate

    Time frame: 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.

    Normal liver function was defined as the value of ALT level lower 40U/L.

  7. Maternal HBsAg loss/seroconversion rate

    Time frame: 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.

    Measurement of the proportion of maternal hepatitis B surface antigen loss and seroconversion.

  8. Incidence of perinatal and partum complications

    Time frame: 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.

    Perinatal and partum complications included hypertensive disorders in pregnancy, gestational diabetes mellitus, fetal growth retardation, premature delivery, premature rupture of membrane, and postpartum hemorrhage.

  9. Birth height

    Time frame: At the time of delivery.

    Measurement of infants' height at the time of delivery.

  10. Birth weight

    Time frame: At the time of delivery.

    Measurement of infants' weight at the time of delivery.

  11. Neonate apgar score at 1 minute

    Time frame: At 1 minute after birth.

    Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.

  12. Neonate apgar score at 5 minutes

    Time frame: At 5 minutes after birth.

    Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.

  13. Incidence of deformity

    Time frame: At the time of delivery; at 1, 7, 12 month postpartum.

    The incidence of baby deformity was recorded during the postpartum follow-up period.

  14. Breastfeeding rate

    Time frame: At birth, at 1 and 7 month follow-up.

    Breast feeding status was assessed in all infants during the postpartum follow-up period.

Sponsors and collaborators

Lead sponsor

Third Affiliated Hospital, Sun Yat-Sen University

Other

Registry information

Official study title

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

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Mar 19, 2018
Registry last updated
Aug 29, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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