Hepatitis B
Conditions
Keywords
mother to child transmission, hepatitis B, tenofovir
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).
Interventions
DRUGTenofovir Disoproxil Fumarate
300 mg daily
Sponsors
Thrasher Research Fund
Shoklo Malaria Research Unit
Chiang Mai University
University of Oxford
Johns Hopkins Bloomberg School of Public Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Masking description
No masking, just one interventional group.
Intervention model description
Single group study.
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 49 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The time (from inclusion through delivery; up to 6 months) to HBV DNA suppression (<100 IU/ml) | Up to 9 months | HBV DNA will be monitored every month |
| The proportion of women with undetectable HBV DNA at delivery | At delivery | HBV DNA will be monitored at delivery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to 9 months | Drug accountability using standard methods (subtracting the number of tablets left from the number of tablets distributed). |
| Proportion of hepatitis B flares in mothers postpartum | 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. |
| The proportion of hepatitis B infections in the offspring at 1 year of age | Between month 2 and 12 month | Testing for HBsAg in children between 2 and 12 months of age. |
| 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) | Up to 9 months | All women will be surveyed at monthly visits and at birth to measure adherence including actionable barriers. |
| 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) | Up to 9 months | Measurement of tenofovir drug levels |
Countries
Thailand
Outcome results
None listed