Clinical trial NCT02995005: Tenofovir in Early Pregnancy to Prevent Mother-to-child Transmission of Hepatitis B Virus
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatitis B
Keywords: mother to child transmission
hepatitis B
tenofovir
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
name: Shoklo Malaria Research Unit
name: Chiang Mai University
name: University of Oxford
First posted: 2016-12-16
Enrollment: 98
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single group study.
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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

Primary outcomes:
measure: The time (from inclusion through delivery; up to 6 months) to HBV DNA suppression (<100 IU/ml)
timeFrame: Up to 9 months
measure: The proportion of women with undetectable HBV DNA at delivery
timeFrame: At delivery
Secondary outcomes:
measure: Proportion of hepatitis B flares in mothers postpartum
timeFrame: Monthly measured for 3 months after stopping TDF.
measure: 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)
timeFrame: Up to 9 months
measure: 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)
timeFrame: Up to 9 months
measure: 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)
timeFrame: Up to 9 months
measure: The proportion of hepatitis B infections in the offspring at 1 year of age
timeFrame: Between month 2 and 12 month
Other outcomes:
Locations:
city: Mae Sot
country: Thailand
facility: Shoklo Malaria Research Unit
Study officials:
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Stephan Ehrhardt, MD
role: PRINCIPAL_INVESTIGATOR
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