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

NCT03468907 | Completed Phase 4 DMC

• 1 other identifier: Safety of anti-viral agents
• Study Type: interventional
• Target: 111
• Locations: 0 countries
• Sites: N/A

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 investigated the safety of antiviral therapy in preventing HBV mother-to-child transmission in pregnant women after discontinuation.

Conditions

Hepatitis B, Chronic

Keywords

hepatitis B virus; exacerbation; antiviral agents; pregnancy; flare

Outcome Measures

Primary Outcomes (1)

• Postpartum flare incidence

  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.

Secondary Outcomes (14)

• Time of flare onset

  Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.

• Proportion of severe flares

  Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.

• Peak ALT during flare

  Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.

• The rate of perinatal transmission

  7 months after birth.

• HBV kinetics in patients

  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.

Study Arms (3)

Early cessation

EXPERIMENTAL

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.

Drug: Telbivudine 600mg; Drug: Tenofovir disoproxil fumarate 300mg

Late cessation

EXPERIMENTAL

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.

Drug: Telbivudine 600mg; Drug: Tenofovir disoproxil fumarate 300mg

Control

NO INTERVENTION

Eligible patients who refused antiviral therapy but consented to the study were assigned to the control arm.

Interventions

Telbivudine 600mg DRUG

Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.

Also known as: Sebivo

Early cessation; Late cessation

Tenofovir disoproxil fumarate 300mg DRUG

Pregnant mothers who opted for antiviral therapy would start on oral TDF 300 mg daily between gestational weeks 24 and 28.

Also known as: Viread

Early cessation; Late cessation

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Third Affiliated Hospital, Sun Yat-Sen University: lead

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

Telbivudine; Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Zhi-liang Gao, PhD

  Third Affiliated Hospital, Sun Yat-Sen University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: The care provider, participant, investigator and outcomes assessor all konw the process.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: January 21, 2018
• First Posted: March 19, 2018
• Study Start: June 1, 2015
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2017
• Last Updated: August 29, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share