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Trial record 116 of 339 for:    hepatitis b | Recruiting, Not yet recruiting, Available Studies

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

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ClinicalTrials.gov Identifier: NCT03468907
Recruitment Status : Not yet recruiting
First Posted : March 19, 2018
Last Update Posted : March 19, 2018
Sponsor:
Information provided by (Responsible Party):
Chao-Shuang Lin, Third Affiliated Hospital, Sun Yat-Sen University

Brief Summary:
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 investigates the safety of antiviral therapy in preventing HBV mother-to-child transmission in pregnant women after discontinuation.

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: Telbivudine 600mg Drug: Tenofovir disoproxil fumarate 300mg Phase 4

Detailed Description:
This is a prospective, open-label, interventional trial, in which patients are to be recruited 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, between March 2018 and December 2020. Pregnant women fulfilling the inclusion and exclusion criteria will be offered participation in the study. All pregnant women who opt for AVT need to sign a consent form and start 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 are measured at baseline(i.e. at screening), every 4 weeks after treatment begins, at the time of delivery, and at 1, 2, 3, 7, 12 month postpartum. AVT is discontinued to the patients with ALT < 2 times ULN, while the other patients with abnormal serum ALT level (≥ 2 times ULN) continued to take antiviral agents and cease AVT at postpartum 6 weeks. Mothers can choose to breastfeed infants one week after the medicine withdrawal. All infants are 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 are tested at birth (before immunization) and again at 7 months. The investigators discuss the postpartum liver function after withdrawal and evaluate the impact of extending the postpartum duration of AVT administered for the prevention of perinatal transmission.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Pregnant mothers who opt for antiviral therapy will start on oral LDT 600 mg or TDF 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28. Antiviral therapy will be discontinued in intrapartum or at postpartum 6 weeks.
Masking: None (Open Label)
Masking Description: The care provider, participant, investigator and outcomes assessor all konw the process.
Primary Purpose: Prevention
Official Title: The Safety of Anti-viral Therapy in Preventing Mother-to-child Transmission of Hepatitis B Virus in Pregnant Women After Discontinuation
Estimated Study Start Date : April 1, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
Experimental: Early cessation
Pregnant mothers who opt for antiviral therapy will start on oral LDT 600 mg or TDF 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28. Antiviral therapy will be discontinued in intrapartum.
Drug: Telbivudine 600mg
Pregnant mothers who opt for antiviral therapy will start on oral LDT 600 mg daily between gestational weeks 24 and 28.
Other Name: Sebivo

Drug: Tenofovir disoproxil fumarate 300mg
Pregnant mothers who opt for antiviral therapy will start on oral TDF 300 mg daily between gestational weeks 24 and 28.
Other Name: Viread

Experimental: Late cessation
Pregnant mothers who opt for antiviral therapy will start on oral LDT 600 mg or TDF 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28. After delivery, mothers cease antiviral treatment at postpartum 6 weeks.
Drug: Telbivudine 600mg
Pregnant mothers who opt for antiviral therapy will start on oral LDT 600 mg daily between gestational weeks 24 and 28.
Other Name: Sebivo

Drug: Tenofovir disoproxil fumarate 300mg
Pregnant mothers who opt for antiviral therapy will start on oral TDF 300 mg daily between gestational weeks 24 and 28.
Other Name: Viread

No Intervention: Control
Eligible patients who refuse antiviral therapy but consent to the study are assigned to the control arm.



Primary Outcome Measures :
  1. Postpartum flare incidence [ Time Frame: From baseline to postpartum 12 months. ]
    Time-to-event measures. Postpartum flare is defined as an alanine aminotransferase (ALT) rise to three times baseline level or five times ULN (40U/L) within 12 months post-delivery. Maternal will be recorded if postpartum flare occurs. At the end of postpartum 12-month follow-up period, postpartum flare incidence will be measured.


Secondary Outcome Measures :
  1. Time of flare onset [ Time Frame: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,7,12 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 1,2,3,7,12 month postpartum. ]
    As per protocol, ALT flares (>5 times baseline level or >10 times ULN) are considered severe adverse events (SAEs).

  3. Peak ALT during flare [ Time Frame: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,7,12 month postpartum. ]
    Peak ALT during postpartum flare.

  4. The rate of perinatal transmission [ Time Frame: 7 months after birth. ]
    Perinatal transmission is 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 1,2,3,7,12 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 1,2,3,7,12 month postpartum. ]
    Normal liver function is 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 1,2,3,7,12 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 1,2,3,7,12 month postpartum. ]
    Perinatal and partum complications include 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 include activity, pulse, grimace, appearance and respiration.

  12. Neonate apgar score at 5 minutes [ Time Frame: At 5 minutes after birth. ]
    Apgar scores of neonates include 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 is recorded during the postpartum follow-up period.

  14. Breastfeeding rate [ Time Frame: At birth, at 1 and 7 month follow-up. ]
    Breast feeding status is assessed in all infants during the postpartum follow-up period.



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03468907


Contacts
Contact: Yiru Chen, MD 0086(020)85252110 chnyiru@126.com
Contact: Chao-shuang Lin, PhD 0086(020)85252110 shuangss@21cn.com

Sponsors and Collaborators
Third Affiliated Hospital, Sun Yat-Sen University
Investigators
Study Chair: Zhi-liang Gao, PhD Third Affiliated Hospital, Sun Yat-Sen University

Responsible Party: Chao-Shuang Lin, Professor, Third Affiliated Hospital, Sun Yat-Sen University
ClinicalTrials.gov Identifier: NCT03468907     History of Changes
Other Study ID Numbers: Safety of anti-viral agents
First Posted: March 19, 2018    Key Record Dates
Last Update Posted: March 19, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data (IPD) is not available to other researchers.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Chao-Shuang Lin, Third Affiliated Hospital, Sun Yat-Sen University:
hepatitis B virus
exacerbation
antiviral agents
pregnancy
flare

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Viral, Human
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Antiviral Agents
Telbivudine
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents