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

27. srpna 2018 aktualizováno: 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.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis (Aktuální)

111

Fáze

  • Fáze 4

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let až 45 let (Dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Ženský

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Prevence
  • Přidělení: Nerandomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: 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.
Lék: Telbivudine 600mg
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
Ostatní jména:
  • Sebivo
Lék: 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.
Ostatní jména:
  • Viread
Experimentální: 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.
Lék: Telbivudine 600mg
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
Ostatní jména:
  • Sebivo
Lék: 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.
Ostatní jména:
  • Viread
Žádný zásah: Control
Eligible patients who refused antiviral therapy but consented to the study were assigned to the control arm.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Postpartum flare incidence
Časové okno: 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.

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Time of flare onset
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: At the time of delivery.
Measurement of infants' height at the time of delivery.
At the time of delivery.
Birth weight
Časové okno: 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
Časové okno: 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
Časové okno: At 5 minutes after birth.
Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.
At 5 minutes after birth.
Incidence of deformity
Časové okno: 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
Časové okno: 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.

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Third Affiliated Hospital, Sun Yat-Sen University

Vyšetřovatelé

  • Studijní židle: Zhi-liang Gao, PhD, Third Affiliated Hospital, Sun Yat-Sen University

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

1. června 2015

Primární dokončení (Aktuální)

31. prosince 2017

Dokončení studie (Aktuální)

31. prosince 2017

Termíny zápisu do studia

První předloženo

21. ledna 2018

První předloženo, které splnilo kritéria kontroly kvality

12. března 2018

První zveřejněno (Aktuální)

19. března 2018

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

29. srpna 2018

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

27. srpna 2018

Naposledy ověřeno

1. srpna 2018

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • Safety of anti-viral agents

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

NE

Popis plánu IPD

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

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

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