Hepatitis B, ChronicPhase 4NCT03468907
The Safety of Anti-viral Therapy in Preventing HBV MTCT in Pregnant Women After Discontinuation
A Phase 4 study testing Telbivudine 600mg and Tenofovir disoproxil fumarate 300mg in people with Hepatitis B, Chronic, run by Third Affiliated Hospital, Sun Yat-Sen University.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Telbivudine 600mg and Tenofovir disoproxil fumarate 300mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 111 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2015to 31 Dec 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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)
Who cannot join
- 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.
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Hepatitis B, Chronic
- Being tested
- Telbivudine 600mg, Tenofovir disoproxil fumarate 300mg
- Keywords
- hepatitis B virus, exacerbation, antiviral agents, pregnancy, flare
- Medical subject headings
- Hepatitis B, Chronic, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Telbivudine 600mgDrug
Also called Sebivo
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
Tenofovir disoproxil fumarate 300mgDrug
Also called Viread
Pregnant mothers who opted for antiviral therapy would start on oral TDF 300 mg daily between gestational weeks 24 and 28.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to postpartum 12 months.
Secondary outcomes (14)
Time of flare onset
Time-to-event measures. Time of the onset of postpartum liver damage.
Measured: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
Proportion of severe flares
As per protocol, ALT flares (>5 times baseline level or >10 times ULN) were considered severe adverse events (SAEs).
Measured: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
Peak ALT during flare
Peak ALT during postpartum flare.
Measured: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
The rate of perinatal transmission
Perinatal transmission was established by detectable HBV DNA and HBsAg levels in the peripheral blood of infants at 7 months.
Measured: 7 months after birth.
HBV kinetics in patients
Changes of HBV viral load in patients treated and not treated with antiviral agents.
Measured: 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
Normal liver function was defined as the value of ALT level lower 40U/L.
Measured: 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
Measurement of the proportion of maternal hepatitis B surface antigen loss and seroconversion.
Measured: 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
Perinatal and partum complications included hypertensive disorders in pregnancy, gestational diabetes mellitus, fetal growth retardation, premature delivery, premature rupture of membrane, and postpartum hemorrhage.
Measured: 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
Measurement of infants' height at the time of delivery.
Measured: At the time of delivery.
Birth weight
Measurement of infants' weight at the time of delivery.
Measured: At the time of delivery.
Neonate apgar score at 1 minute
Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.
Measured: At 1 minute after birth.
Neonate apgar score at 5 minutes
Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.
Measured: At 5 minutes after birth.
Incidence of deformity
The incidence of baby deformity was recorded during the postpartum follow-up period.
Measured: At the time of delivery; at 1, 7, 12 month postpartum.
Breastfeeding rate
Breast feeding status was assessed in all infants during the postpartum follow-up period.
Measured: At birth, at 1 and 7 month follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2018
- Study start1 Jun 2015
- Primary completion31 Dec 2017
- Study completion31 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Lead sponsor
- Third Affiliated Hospital, Sun Yat-Sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chao-Shuang Lin, Third Affiliated Hospital, Sun Yat-Sen University
- Investigators
- Zhi-liang Gao, PhD, Study chair, Third Affiliated Hospital, Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03468907
- Sponsor's protocol ID
- Safety of anti-viral agents
- Status last verified
- Aug 2018
- First submitted
- 21 Jan 2018
- Last updated
- 29 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) is not available to other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety of Anti-viral Therapy in Preventing Mother-to-child Transmission of Hepatitis B Virus in Pregnant Women After Discontinuation
- ClinicalTrials.gov ID
- NCT03468907
- Acronym / sponsor ID
- Safety of anti-viral agents
- Conditions
- Hepatitis B, Chronic
- Keywords
- hepatitis B virus, exacerbation, antiviral agents, pregnancy, flare
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 111 participants (actual)
- Lead sponsor
- Third Affiliated Hospital, Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 1 Jun 2015 (actual)
- Primary completion
- 31 Dec 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 19 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Early cessation | Experimental | Drug: Telbivudine 600mg, Drug: Tenofovir disoproxil fumarate 300mgPregnant 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. |
| Late cessation | Experimental | Drug: Telbivudine 600mg, Drug: Tenofovir disoproxil fumarate 300mgPregnant 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. |
| Control | No intervention | –Eligible patients who refused antiviral therapy but consented to the study were assigned to the control arm. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Telbivudine 600mgAlso: SebivoPregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28. | Drug | Early cessation, Late cessation |
| Tenofovir disoproxil fumarate 300mgAlso: VireadPregnant mothers who opted for antiviral therapy would start on oral TDF 300 mg daily between gestational weeks 24 and 28. | Drug | Early cessation, Late cessation |
Primary outcome
Postpartum flare incidence
Time frame: 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.
14 secondary outcomes
Time of flare onset
Time frame: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
Proportion of severe flares
Time frame: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
Peak ALT during flare
Time frame: Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
The rate of perinatal transmission
Time frame: 7 months after birth.
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 1,2,3,6,12 month postpartum.
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 1,2,3,6,12 month postpartum.
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 1,2,3,6,12 month postpartum.
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 1,2,3,6,12 month postpartum.
Birth height
Time frame: At the time of delivery.
Birth weight
Time frame: At the time of delivery.
Neonate apgar score at 1 minute
Time frame: At 1 minute after birth.
Neonate apgar score at 5 minutes
Time frame: At 5 minutes after birth.
Incidence of deformity
Time frame: At the time of delivery; at 1, 7, 12 month postpartum.
Breastfeeding rate
Time frame: At birth, at 1 and 7 month follow-up.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2018.
- Individual participant dataSharing planned: No. Individual participant data (IPD) is not available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhi-liang Gao, PhD study chair
Third Affiliated Hospital, Sun Yat-Sen University
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Telbivudine 600mg and Tenofovir disoproxil fumarate 300mg in people with Hepatitis B, Chronic, run by Third Affiliated Hospital, Sun Yat-Sen University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postpartum flare incidence (time frame: From baseline to postpartum 12 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2018.