Hepatitis B Infection
Conditions
Keywords
perinatal infection, hepatitis B in pregnancy
Brief summary
Hepatitis B virus is an infection that can be easily transmitted from women to newborns at the time of delivery. Our objective is to identify novel options that are effective and safe in preventing perinatal transmission of hepatitis B in Africa. The REVERT-B study (Reducing Vertical Transmission of Hepatitis B in Africa) is a clinical trial designed to test a new strategy of using antiviral medication in high-risk pregnant women and newborns to reduce the risk of hepatitis B transmission. The study will measure efficacy, safety, tolerability and adherence to medication.
Detailed description
The REVERT-B trial is a multi-center, phase III, randomized 2x2 factorial study designed to test the efficacy of early maternal TDF vs standard duration and neonatal 3TC prophylaxis compared to matching placebo in preventing HBV MTCT. Eligible pregnant women with HBV in prenatal care (n=450) will be randomized 1:1:1:1 to one of four maternal and neonatal prophylaxis combinations (shown as A-D in the figure below). Women will initiate daily oral TDF early (2nd trimester) or at the standard time per WHO guidelines (3rd trimester) and will continue TDF until delivery. The current WHO standard of care in pregnant women with HBV (EAg+) in Cameroon is TDF prophylaxis from 28 weeks until delivery. Newborns will receive liquid 3TC or matching placebo for the first six months of life to provide coverage until the vaccine series is complete. All infants in the study will be offered the 4-dose HBV vaccine series starting at birth. The 2x2 factorial design allows for two simultaneous studies where we first assess efficacy of early maternal prophylaxis (Aim 1) and secondarily assess efficacy of neonatal prophylaxis (Aim 2). The study endpoint for both aims is the MTCT rate (proportion of infants HBsAg+) at 6-9 months of age. Women and infants will be followed until 6-9 months after delivery and subaims will assess safety and adherence to maternal TDF and neonatal 3TC. Plasma testing will be used to measure medication adherence.
Interventions
DRUGTenofovir Disoproxil Fumarate
oral TDF medication 300 mg daily
Oral lamivudine with weight-based dosing BID from birth until 6 months of age
Sponsors
University of Alabama at Birmingham
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Pregnant women will be randomized in open label fashion to early or late initiation of TDF. Infants will be randomized to receive lamivudine or matching placebo.
Intervention model description
2x2 factorial
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* prenatal clinic patient, * age ≥16 years, * 14-32 weeks gestational age according to clinic dating based on LMP or ultrasound, * active hepatitis B with risk of vertical transmission (HBsAg+ AND HBV DNA \>1000 IU/ML or HbEAg+), * plan to receive follow up care and deliver at study facility, * capable of providing informed consent.
Exclusion criteria
* HIV positive (according to HIV antibody testing performed at the initial prenatal visit) * known liver cirrhosis or end-stage liver disease, * elevated liver enzymes (ALT \>150 \[5x upper limit of normal\]), * elevated serum creatinine (\>1.4 mg/dl) * currently taking tenofovir medication * allergy or intolerance to tenofovir study medication, * known fetal anomaly in the current pregnancy, * clinical illness requiring hospitalization at the time of enrollment * evidence of early labor at the time of enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vertical Transmission of hepatitis B Infection | 6-9 months of age | The proportion of infants with Hepatitis B surface antigen positivity (SAg+) |
| Virologic Suppression | at/near delivery | The proportion of women with a suppressed HBV DNA viral load (\<10 IU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hepatitis B Flare | Within 12-24 weeks after delivery | Increase in ALT (\>2x ULN) after stopping TDF at delivery |
| Incident HIV infection during pregnancy | at delivery | Maternal HIV infection with seroconversion to positive test |
| Vertical Transmission and Mode of Delivery | infant testing at 6-9 months of age | compare rate of HBV vertical transmission between cesarean and vaginal delivery |
| Time to Virologic Suppression on TDF | at/near delivery | Assess number of weeks to HBV DNA \< 10 IU/ML |
| Neonatal HBV Viremia | within 30 days of birth | Detection of HBV DNA in plasma |
| Maternal Adherence to TDF | within one month of initiation of therapy through time of delivery | HPLC measurement of serum and/or self-report |
| Infant Adherence to Lamivudine | 12-24 weeks after starting Lamivudine | HPLC measurement of serum and/or maternal report |
| Preterm delivery | assessed at delivery | Delivery \<37 weeks gestational age |
| Low Birth Weight | at birth | Infant birth weight \<2500 grams |
| spontaneous abortion | between enrollment and 28 weeks gestational age | unanticipated loss of pregnancy |
| intrauterine fetal demise | at/after 28 weeks gestational age | unanticipated loss of pregnancy |
| Neonatal Death | within 28 days of birth | Mortality after Live Birth |
| TDF Tolerability | from enrollment through delivery | Self-reported TDF tolerability and observed first dose during pregnancy |
| Composite Adverse Birth Outcomes | during pregnancy or up to 28 days after delivery | PTD, SAB, IUFD, neonatal death |
| Lamivudine Tolerability | birth through 24 weeks of age | Maternal reported infant lamivudine tolerability |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJodie Dionne, MD, MSPH
University of Alabama at Birmingham
Outcome results
None listed