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NCT Number: NCT02995005

Tenofovir in Early Pregnancy to Prevent Mother-to-child Transmission of Hepatitis B Virus

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains the major mode of transmission in most high and intermediate HBV endemic areas, despite existing WHO immunoprophylaxis recommendations. This immunoprophylaxis regimen, if given optimally, can prevent 75-80% of HBV MTCT, but optimal implementation is difficult because it requires administering monovalent HBV vaccine and hepatitis B immunoglobulin (HBIg) within 24 hours of birth. Due to the barriers of giving HBIg, the World Health Organization (WHO) states, "…owing to concerns related to supply, safety and cost, the use of HBIg is not feasible in most settings." Clearly, global control of HBV transmission will require improved MTCT prevention. Therefore, the investigators hypothesize that treating HBV early in pregnancy will lead to undetectable HBV DNA levels at delivery and prevention of MTCT of HBV without HBIg; a concept that has already been proven with HIV. Tenofovir disoproxil fumarate (TDF), an approved anti-HBV drug, is promising to prevent MTCT of HBV due to its high potency against hepatitis B and its safety record in pregnant women. A randomized, controlled clinical trial (RCT) will be necessary to determine if TDF given to HBV-infected pregnant women early in pregnancy plus vaccine to the newborn can decrease MTCT of HBV without HBIg. However, before embarking on a RCT, several critical knowledge gaps need to be addressed including the ideal timing for TDF initiation. The purpose of this proposal is to address these knowledge gaps.

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Key information

Conditions

Hepatitis B Blood-Borne Infections Communicable Diseases DNA Virus Infections Digestive System Diseases Hepadnaviridae Infections Hepatitis Hepatitis, Viral, Human Infections Liver Diseases Virus Diseases

Age range

16 year–49 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Shoklo Malaria Research Unit

Mae Sot, Thailand

About this study

The investigators hypothesize that anti-HBV therapy given in the late first or early second trimester achieves undetectable HBV DNA at delivery in >=95% of pregnant women with chronic hepatitis B. The one-arm, open-label, interventional study aims: 1, To estimate the time to complete HBV DNA suppression (<100 IU/ml) in 170 HBV DNA positive women who start TDF in the late first or early second trimester; and to estimate the proportion of women with HBV DNA <100 IU/ml at delivery. 2, To address potential barriers to and the efficacy of implementing TDF in early pregnancy to prevent mother-to-child transmission of hepatitis B. The investigators will measure potential barriers to acceptability and effectiveness of this intervention: adherence, potential hepatitis B flares in mothers (safety), and the proportion of hepatitis B infections in the offspring at 1 year of age (efficacy).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Pregnant women aged 18 and over
  • HBsAg positive
  • In the 12th-20th week of pregnancy
  • Willing to take TDF daily during pregnancy
  • Providing written informed consent
  • Plans to deliver at Shoklo Malaria Research Unit (SMRU)
  • Able and willing to comply with study requirements

Exclusion criteria

  • Anti-HIV positive
  • Negative qualitative HBV DNA if HBeAg negative
  • On immunosuppressive therapy
  • Elevated creatinine
  • History of kidney disease
  • Short cervix
  • History of pregnancy complications or prior pre-term labor

Treatment and study plan

Tenofovir disoproxil fumarate

Drug

300 mg daily

Other names: Viread

Primary outcomes

  1. The time (from inclusion through delivery; up to 6 months) to HBV DNA suppression (<100 IU/ml)

    Time frame: Up to 9 months

    HBV DNA will be monitored every month

  2. The proportion of women with undetectable HBV DNA at delivery

    Time frame: At delivery

    HBV DNA will be monitored at delivery.

Secondary outcomes

  1. Proportion of hepatitis B flares in mothers postpartum

    Time frame: Monthly measured for 3 months after stopping TDF.

    All women will continue on study for 3 months after stopping TDF to measure their alanine aminotransferase (ALT) and aspartate aminotransferase (AST) monthly to detect a flare, which will be defined as >5x baseline or >10x the upper limit of normal. If at the end of the 3 months, there has been no change in ALT and AST, then the mothers will be discharged from the study. If there is an increase in liver enzymes but not a true flare, they will be followed for an additional 3 months with monthly ALT testing.

  2. The proportion of women who adhered to TDF treatment during the course of the study (from inclusion through 1 month after delivery; up to 7 months; drug levels)

    Time frame: Up to 9 months

    Measurement of tenofovir drug levels

  3. The proportion of women who adhered to TDF treatment during the course of the study (from inclusion through 1 month after delivery; up to 7 months; drug accountability)

    Time frame: Up to 9 months

    Drug accountability using standard methods (subtracting the number of tablets left from the number of tablets distributed).

  4. The proportion of women who adhered to TDF treatment during the course of the study (from inclusion through 1 month after delivery; up to 7 months; questionnaire)

    Time frame: Up to 9 months

    All women will be surveyed at monthly visits and at birth to measure adherence including actionable barriers.

  5. The proportion of hepatitis B infections in the offspring at 1 year of age

    Time frame: Between month 2 and 12 month

    Testing for HBsAg in children between 2 and 12 months of age.

Sponsors and collaborators

Lead sponsor

Johns Hopkins Bloomberg School of Public Health

Other

Collaborators

  • Chiang Mai University
  • Shoklo Malaria Research Unit
  • Thrasher Research Fund
  • University of Oxford

Registry information

Official study title

Prevention of Mother-to-child Transmission of Hepatitis B Virus: a One Arm, Open Label Intervention Study to Estimate the Optimal Timing of Tenofovir (TDF) in Pregnancy

Important dates

Study start
2018
Primary completion
2023
Study completion
2023
First posted
Dec 16, 2016
Registry last updated
Feb 6, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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