- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT03468907
The Safety of Anti-viral Therapy in Preventing HBV MTCT in Pregnant Women After Discontinuation
27. August 2018 aktualisiert von: 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.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Interventionell
Einschreibung (Tatsächlich)
111
Phase
- Phase 4
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre bis 45 Jahre (Erwachsene)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Weiblich
Beschreibung
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.
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Verhütung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
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.
|
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
Andere Namen:
Pregnant mothers who opted for antiviral therapy would start on oral TDF 300 mg daily between gestational weeks 24 and 28.
Andere Namen:
|
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.
|
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
Andere Namen:
Pregnant mothers who opted for antiviral therapy would start on oral TDF 300 mg daily between gestational weeks 24 and 28.
Andere Namen:
|
Kein Eingriff: Control
Eligible patients who refused antiviral therapy but consented to the study were assigned to the control arm.
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Postpartum flare incidence
Zeitfenster: 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.
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Time of flare onset
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: At the time of delivery.
|
Measurement of infants' height at the time of delivery.
|
At the time of delivery.
|
Birth weight
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: At 5 minutes after birth.
|
Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.
|
At 5 minutes after birth.
|
Incidence of deformity
Zeitfenster: 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
Zeitfenster: 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.
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Ermittler
- Studienstuhl: Zhi-liang Gao, PhD, Third Affiliated Hospital, Sun Yat-Sen University
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
1. Juni 2015
Primärer Abschluss (Tatsächlich)
31. Dezember 2017
Studienabschluss (Tatsächlich)
31. Dezember 2017
Studienanmeldedaten
Zuerst eingereicht
21. Januar 2018
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
12. März 2018
Zuerst gepostet (Tatsächlich)
19. März 2018
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
29. August 2018
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
27. August 2018
Zuletzt verifiziert
1. August 2018
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Verdauungssystems
- RNA-Virusinfektionen
- Viruserkrankungen
- Infektionen
- Durch Blut übertragene Infektionen
- Übertragbare Krankheiten
- Leberkrankheiten
- Hepatitis, viral, menschlich
- Hepadnaviridae-Infektionen
- DNA-Virusinfektionen
- Enterovirus-Infektionen
- Picornaviridae-Infektionen
- Hepatitis, chronisch
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, chronisch
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antiinfektiva
- Antivirale Mittel
- Reverse-Transkriptase-Inhibitoren
- Inhibitoren der Nukleinsäuresynthese
- Enzym-Inhibitoren
- Anti-HIV-Agenten
- Antiretrovirale Mittel
- Tenofovir
- Telbivudin
Andere Studien-ID-Nummern
- Safety of anti-viral agents
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
NEIN
Beschreibung des IPD-Plans
Individual participant data (IPD) is not available to other researchers.
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Nein
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Nein
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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