Reducing Vertical Transmission of Hepatitis B in Africa

Phase 3

Recruiting

Interventions: Drug: Lamivudine Oral Solution
Drug: Tenofovir Disoproxil Fumarate

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.

Recruitment & Eligibility

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 HBeAg+ or HBV DNA >1000 IU/ML),
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 >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.

Arm && Interventions

Group	Intervention	Description
Newborn Infants - Lamivudine	Lamivudine Oral Solution	Infants exposed to HBV at birth will be randomized to receive oral lamivudine post-exposure prophylaxis or matching placebo. Medication will be administered twice daily for 6 months.
Pregnant Women - Tenofovir	Tenofovir Disoproxil Fumarate	Women will be randomized to early initiation (enrollment at 14-28 weeks pregnant) vs standard initiation (at 28 weeks pregnant) of tenofovir disoproxil fumarate (TDF) 300 mg daily oral medication until delivery.

Primary Outcome Measures

Name	Time	Method
Virologic Suppression	at delivery	The proportion of women with a suppressed HBV DNA viral load (\<10 IU/mL).
Vertical Transmission of hepatitis B Infection	6-9 months of age	The proportion of infants with Hepatitis B surface antigen positivity (SAg+)

Secondary Outcome Measures

Name	Time	Method
Incident HIV infection during pregnancy	at delivery	Maternal HIV infection with seroconversion to positive test
Retention in Prenatal Care	assessed at time of delivery	at least 4 ANC visits after 28 weeks GA
Infant Adherence to 3TC	24 weeks after starting 3TC	HPLC measurement of serum
Hepatitis B Flare	24 weeks after delivery	Increase in ALT (\>2x ULN) after stopping TDF at delivery
Preterm delivery	assessed at delivery	Delivery \<37 weeks gestational age
In utero HBV infection	at birth	HBV infection (SAg+, PCR positive)
Maternal Adherence to TDF	at delivery	HPLC measurement of serum
Composite Adverse Birth Outcomes	during pregnancy or up to 28 days after delivery	PTD, SAB, IUFD, neonatal death

Locations (1): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States