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

27 de agosto de 2018 atualizado por: Chao-Shuang Lin, Third Affiliated Hospital, Sun Yat-Sen University

The Safety of Anti-viral Therapy in Preventing Mother-to-child Transmission of Hepatitis B Virus 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.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Real)

111

Estágio

  • Fase 4

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 45 anos (Adulto)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Fêmea

Descrição

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.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Prevenção
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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.
Medicamento: Telbivudine 600mg
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
Outros nomes:
  • Sebivo
Medicamento: 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.
Outros nomes:
  • Viread
Experimental: 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.
Medicamento: Telbivudine 600mg
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
Outros nomes:
  • Sebivo
Medicamento: 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.
Outros nomes:
  • Viread
Sem intervenção: Control
Eligible patients who refused antiviral therapy but consented to the study were assigned to the control arm.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Postpartum flare incidence
Prazo: 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.
From baseline to postpartum 12 months.

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Time of flare onset
Prazo: 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.
Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
Proportion of severe flares
Prazo: 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).
Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
Peak ALT during flare
Prazo: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
Peak ALT during postpartum flare.
Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
The rate of perinatal transmission
Prazo: 7 months after birth.
Perinatal transmission was established by detectable HBV DNA and HBsAg levels in the peripheral blood of infants at 7 months.
7 months after birth.
HBV kinetics in patients
Prazo: 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.
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
Prazo: 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.
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.
Maternal HBsAg loss/seroconversion rate
Prazo: 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.
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
Prazo: 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.
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.
Birth height
Prazo: At the time of delivery.
Measurement of infants' height at the time of delivery.
At the time of delivery.
Birth weight
Prazo: At the time of delivery.
Measurement of infants' weight at the time of delivery.
At the time of delivery.
Neonate apgar score at 1 minute
Prazo: At 1 minute after birth.
Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.
At 1 minute after birth.
Neonate apgar score at 5 minutes
Prazo: At 5 minutes after birth.
Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.
At 5 minutes after birth.
Incidence of deformity
Prazo: At the time of delivery; at 1, 7, 12 month postpartum.
The incidence of baby deformity was recorded during the postpartum follow-up period.
At the time of delivery; at 1, 7, 12 month postpartum.
Breastfeeding rate
Prazo: At birth, at 1 and 7 month follow-up.
Breast feeding status was assessed in all infants during the postpartum follow-up period.
At birth, at 1 and 7 month follow-up.

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Third Affiliated Hospital, Sun Yat-Sen University

Investigadores

  • Cadeira de estudo: Zhi-liang Gao, PhD, Third Affiliated Hospital, Sun Yat-Sen University

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

1 de junho de 2015

Conclusão Primária (Real)

31 de dezembro de 2017

Conclusão do estudo (Real)

31 de dezembro de 2017

Datas de inscrição no estudo

Enviado pela primeira vez

21 de janeiro de 2018

Enviado pela primeira vez que atendeu aos critérios de CQ

12 de março de 2018

Primeira postagem (Real)

19 de março de 2018

Atualizações de registro de estudo

Última Atualização Postada (Real)

29 de agosto de 2018

Última atualização enviada que atendeu aos critérios de controle de qualidade

27 de agosto de 2018

Última verificação

1 de agosto de 2018

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • Safety of anti-viral agents

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Descrição do plano IPD

Individual participant data (IPD) is not available to other researchers.

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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