Reducing Vertical Transmission of Hepatitis B in Africa

Phase 3Active Not RecruitingNCT04704024

University of Alabama at Birmingham334 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Conditions

Hepatitis B Infection

Interventions

Tenofovir Disoproxil FumarateDRUG

oral TDF medication 300 mg daily

Lamivudine Oral SolutionDRUG

Oral lamivudine with weight-based dosing BID from birth until 6 months of age

Eligibility

Sex: FEMALEMin age: 16 YearsMax age: 50 Years

Medical Language ↔ Plain English

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.

Locations (1)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Outcomes

Primary Outcomes

Vertical Transmission of hepatitis B Infection

The proportion of infants with Hepatitis B surface antigen positivity (SAg+)

Time frame: 6-9 months of age

Virologic Suppression

The proportion of women with a suppressed HBV DNA viral load (\<10 IU/mL).

Time frame: at/near delivery

Secondary Outcomes

Preterm delivery

Delivery \<37 weeks gestational age

Time frame: assessed at delivery

Low Birth Weight

Infant birth weight \<2500 grams

Time frame: at birth

spontaneous abortion

unanticipated loss of pregnancy

Time frame: between enrollment and 28 weeks gestational age

intrauterine fetal demise

unanticipated loss of pregnancy

Time frame: at/after 28 weeks gestational age

Neonatal Death

Mortality after Live Birth

Time frame: within 28 days of birth

Composite Adverse Birth Outcomes

PTD, SAB, IUFD, neonatal death

Time frame: during pregnancy or up to 28 days after delivery

Maternal Adherence to TDF

HPLC measurement of serum and/or self-report

Data from ClinicalTrials.gov

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