Clinical trial NCT04704024: Reducing Vertical Transmission of Hepatitis B in Africa
Official title: A Phase III, Randomized, 2x2 Factorial Trial to Assess the Efficacy of Antiviral Therapy in Women and Infants in Reducing Vertical Transmission of Hepatitis B in Africa
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hepatitis B Infection
Keywords: perinatal infection, hepatitis B in pregnancy
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2021-01-11
Enrollment: 450
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 2x2 factorial
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Vertical Transmission of hepatitis B Infection
timeFrame: 6-9 months of age
measure: Virologic Suppression
timeFrame: at delivery
Secondary outcomes:
measure: In utero HBV infection
timeFrame: at birth
measure: Maternal Adherence to TDF
timeFrame: 8 weeks after starting medication
measure: Maternal Adherence to TDF
timeFrame: at delivery
measure: Infant Adherence to 3TC
timeFrame: 12 weeks after starting 3TC
measure: Infant Adherence to 3TC
timeFrame: 24 weeks after starting 3TC
measure: Hepatitis B Flare
timeFrame: 12 weeks after delivery
measure: Hepatitis B Flare
timeFrame: 24 weeks after delivery
measure: Preterm delivery
timeFrame: assessed at delivery
measure: Composite Adverse Birth Outcomes
timeFrame: during pregnancy or up to 28 days after delivery
measure: Incident HIV infection during pregnancy
timeFrame: at delivery
measure: Retention in Prenatal Care
timeFrame: assessed at time of delivery
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Jodie Dionne, MD, MSPH
role: PRINCIPAL_INVESTIGATOR
References: