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

This study is ongoing, but not recruiting participants.
Gilead Sciences
Information provided by (Responsible Party):
New Discovery LLC
ClinicalTrials.gov Identifier:
First received: November 30, 2011
Last updated: June 7, 2015
Last verified: June 2015

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.

Condition Intervention Phase
Hepatitis B Infection
Chronic Infection
Drug: TDF treatment
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Tenofovir Disoproxil Fumarate in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus in Highly Viremic Mothers

Resource links provided by NLM:

Further study details as provided by New Discovery LLC:

Primary Outcome Measures:
  • Measure the number of infants who have HBV infection at the age of 28 weeks [ Time Frame: From the date of birth to age of 28 weeks ] [ Designated as safety issue: No ]
  • Assessment of the safety and tolerability of TDF, measure the number of participants and paired infants with adverse events [ Time Frame: From the date of randomization until 28 weeks of postpartum. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Measure maternal HBV DNA reduction during the study period when compared to the baseline [ Time Frame: From the date of radomization until delivery ] [ Designated as safety issue: Yes ]
  • percentage of mothers with sero-negativity or sero-conversion of HBsAg and/or HBeAg in each group for comparison [ Time Frame: From the date of randomization until 28 weeks of postpartum. ] [ Designated as safety issue: Yes ]

Enrollment: 200
Study Start Date: December 2011
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Control arm: HBIG & vaccine for infants
Provide standard of care to mothers and standard immunoprophylaxis to their infants
Experimental: TDF treatment arm
tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum for mothers and standard immunoprophylaxis to their infants
Drug: 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.
Other Name: Viread, Tenofovir, TDF, Hepatitis B-IgG, Hepatitis B vaccine

Detailed Description:
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.

Ages Eligible for Study:   20 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Major 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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01488526

China, Chongqing
Southwest Hospital
Chongqing, Chongqing, China, 400038
China, Hebei
The Fifth Hospital of Shijiazhuang
Shijiazhuang, Hebei, China, 050021
China, Henan
Nanyang Central Hospital
Nanyang, Henan, China, 473000
China, Jiangsu
The Second Affiliated Hospital of the Southeast University
Nanjing, Jiangsu, China, 210003
China, Jilin
Hepatobiliary Disease Hospital of Jilin Province
Chang Chun, Jilin, China, 130062
Sponsors and Collaborators
New Discovery LLC
Gilead Sciences
Study Chair: Calvin Q Pan, MD Leading Principle Investigator, Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New York
Study Director: Zhongping Duan, MD Capital Medical University
Principal Investigator: Shuqin Zhang, MD Hepatobiliary Disease Hospital of Jilin Province, Jilin, China
Principal Investigator: Erhei Dai, MD The Fifth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China
Principal Investigator: Guorong Han, MD The Second Affiliated Hospital of the Southeast University, Nanjing, China
Principal Investigator: Huaihong Zhang, MD Nanyang Central Hospital, Nanyang, Henan, China
Principal Investigator: Yuming Wang, MD Southwest Hospital, Chongqing, Chongqing, China
  More Information

No publications provided

Responsible Party: New Discovery LLC
ClinicalTrials.gov Identifier: NCT01488526     History of Changes
Other Study ID Numbers: IN-US 174-0174
Study First Received: November 30, 2011
Last Updated: June 7, 2015
Health Authority: China: Ethics Committee

Keywords provided by New Discovery LLC:
Hepatitis B
Vertical transmission
Antiviral treatment

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

ClinicalTrials.gov processed this record on November 24, 2015