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

27 augustus 2018 bijgewerkt door: 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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

111

Fase

  • Fase 4

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 45 jaar (Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Vrouw

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Preventie
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Geneesmiddel: Telbivudine 600mg
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
Andere namen:
  • Sebivo
Geneesmiddel: 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.
Andere namen:
  • Viread
Experimenteel: 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.
Geneesmiddel: Telbivudine 600mg
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
Andere namen:
  • Sebivo
Geneesmiddel: 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.
Andere namen:
  • Viread
Geen tussenkomst: Control
Eligible patients who refused antiviral therapy but consented to the study were assigned to the control arm.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Postpartum flare incidence
Tijdsspanne: 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.

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Time of flare onset
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: At the time of delivery.
Measurement of infants' height at the time of delivery.
At the time of delivery.
Birth weight
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: At 5 minutes after birth.
Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.
At 5 minutes after birth.
Incidence of deformity
Tijdsspanne: 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
Tijdsspanne: 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.

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Third Affiliated Hospital, Sun Yat-Sen University

Onderzoekers

  • Studie stoel: Zhi-liang Gao, PhD, Third Affiliated Hospital, Sun Yat-Sen University

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 juni 2015

Primaire voltooiing (Werkelijk)

31 december 2017

Studie voltooiing (Werkelijk)

31 december 2017

Studieregistratiedata

Eerst ingediend

21 januari 2018

Eerst ingediend dat voldeed aan de QC-criteria

12 maart 2018

Eerst geplaatst (Werkelijk)

19 maart 2018

Updates van studierecords

Laatste update geplaatst (Werkelijk)

29 augustus 2018

Laatste update ingediend die voldeed aan QC-criteria

27 augustus 2018

Laatst geverifieerd

1 augustus 2018

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • Safety of anti-viral agents

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Beschrijving IPD-plan

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

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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