Tenofovir in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus

NCT ID: NCT01488526

Last Updated: 2019-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-03-01

Study Completion Date

2018-06-28

Brief Summary

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Immunoprophylaxis failure of hepatitis B virus (HBV) leading to vertical transmission remains a concern and has been reported in approximately 8-15% of infants born to hepatitis B e antigen (HBeAg) positive mothers with high levels of HBV DNA. Maternal HBV DNA \> 6log10 copies/mL (or \>200,000 IU/mL) is the major risk for the mother-to-child transmission. Prior observational studies have shown that antiviral therapy including lamivudine or telbivudine use during late pregnancy can safely reduce the rate of vertical transmission in this special population compared to untreated patients.

Tenofovir Disoproxil (TDF), a pregnancy category B medication, reduces HBV DNA and normalizes serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB) with few adverse effects. Two aspects on tenofovir use in pregnancy will be evaluated prospectively in this study:

1. The data on its tolerability and safety in HBeAg+ pregnant women with HBV DNA \> 6log10 copies/mL (or \> 200,000 IU/mL) during late pregnancy and infants.
2. Its efficacy in the reduction of HBV vertical transmission rate.

Detailed Description

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Eligible mothers will be randomized (1:1) to either TDF-treated group or untreated group with about 100 subjects in each arm. The treatment group will receive TDF starting at week 30-32 of gestation until week 4 postpartum; follow up will continue until post-partum week 28 and infants age of 28 weeks. Untreated group will receive the standard of care with similar follow-up schedule as the treatment group.

Conditions

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Hepatitis B Infection Chronic Infection Viremia

Keywords

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Hepatitis B Vertical transmission Pregnancy Antiviral treatment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Control arm: HBIG & vaccine for infants

Provide standard of care to mothers and standard immunoprophylaxis to their infants

Group Type NO_INTERVENTION

No interventions assigned to this group

TDF treatment arm

tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum for mothers and standard immunoprophylaxis to their infants

Group Type EXPERIMENTAL

TDF treatment

Intervention Type DRUG

About 100 mothers treated with tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum, then observed to the end of the study at post-partum week 28, paired infants received standard HBV prophylaxis.

Interventions

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TDF treatment

About 100 mothers treated with tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum, then observed to the end of the study at post-partum week 28, paired infants received standard HBV prophylaxis.

Intervention Type DRUG

Other Intervention Names

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Viread, Tenofovir, TDF, Hepatitis B-IgG, Hepatitis B vaccine

Eligibility Criteria

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Inclusion Criteria

* documented CHB infection with HBsAg positive \> 6 months
* HBeAg+ CHB pregnant women
* gestational age between 30-32 weeks
* HBV DNA \> 6 log10 copies/mL (or \>200,000 IU/mL)
* both mother and father of the child are willing to consent for the study

Exclusion Criteria

* co-infection with hepatitis A, C, D, E, HIV-1 or sexually transmitted disease (STD)
* decompensated liver disease or significant co-morbidity
* history of abortion, or diagnosis of fetal defect, or congenital malformation in prior pregnancy
* antiviral used within six months prior to this pregnancy, or history of renal or tubular function impairment due to adefovir.
* requirement for other medication during pregnancy to manage other chronic disease(s) or concurrent treatment with immune-modulators, cytotoxic drugs, or steroids
* the biological father of the child had CHB
* clinical signs of threatened miscarriage in early pregnancy
* evidence of hepatocellular carcinoma
* maternal alanine aminotransferase (ALT) \> or = 5 x upper limit of normal (U/mL), or Total Bilirubin \> or = 2, or glomerular filtration rate (GFR) \< 100, or Albumin \< 25 g/L
* evidence of fetal deformity by ultrasound examination
* patient is participating other clinical study
Minimum Eligible Age

20 Years

Maximum Eligible Age

35 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

New Discovery LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Calvin Q Pan, MD

Role: STUDY_CHAIR

Leading Principle Investigator, Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New York

Zhongping Duan, MD

Role: STUDY_DIRECTOR

Capital Medical University

Shuqin Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Hepatobiliary Disease Hospital of Jilin Province, Jilin, China

Erhei Dai, MD

Role: PRINCIPAL_INVESTIGATOR

The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China

Guorong Han, MD

Role: PRINCIPAL_INVESTIGATOR

The Second Affiliated Hospital of the Southeast University, Nanjing, China

Huaihong Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Nanyang Central Hospital, Nanyang, Henan, China

Yuming Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Southwest Hospital, Chongqing, Chongqing, China

Locations

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Southwest Hospital

Chongqing, Chongqing Municipality, China

Site Status

The Fifth Hospital of Shijiazhuang

Shijiazhuang, Hebei, China

Site Status

Nanyang Central Hospital

Nanyang, Henan, China

Site Status

The Second Affiliated Hospital of the Southeast University

Nanjing, Jiangsu, China

Site Status

Hepatobiliary Disease Hospital of Jilin Province

Changchun, Jilin, China

Site Status

Countries

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China

References

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Pan CQ, Dai E, Duan Z, Han G, Zhao W, Wang Y, Zhang H, Zhu B, Jiang H, Zhang S, Zhang X, Zou H, Chen X, Chen Y. Long-term safety of infants from mothers with chronic hepatitis B treated with tenofovir disoproxil in China. Gut. 2022 Apr;71(4):798-806. doi: 10.1136/gutjnl-2020-322719. Epub 2021 Mar 31.

Reference Type DERIVED
PMID: 33789963 (View on PubMed)

Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, Zhang H, Zou H, Zhu B, Zhao W, Jiang H; China Study Group for the Mother-to-Child Transmission of Hepatitis B. Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load. N Engl J Med. 2016 Jun 16;374(24):2324-34. doi: 10.1056/NEJMoa1508660.

Reference Type DERIVED
PMID: 27305192 (View on PubMed)

Other Identifiers

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IN-US 174-0174

Identifier Type: -

Identifier Source: org_study_id