Reducing Vertical Transmission of Hepatitis B in Africa

Hepatitis B Infection Clinical Trial

— REVERT-B  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04704024
• Other study ID #: IRB-300006586
• Secondary ID: 5R01HD101545
• Status: Recruiting
• Phase: Phase 3
• Start date: September 3, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: University of Alabama at Birmingham
• Contact: Jodie Dionne, MD, MSPH
• Phone: 2059756530
• Email: jdionne[@]uabmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years to 50 Years

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B Infection

Intervention

Drug:
• Tenofovir Disoproxil Fumarate
oral TDF medication 300 mg daily
• Lamivudine Oral Solution
Oral lamivudine with weight-based dosing BID from birth until 6 months of age

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vertical Transmission of hepatitis B Infection	The proportion of infants with Hepatitis B surface antigen positivity (SAg+)	6-9 months of age
Primary	Virologic Suppression	The proportion of women with a suppressed HBV DNA viral load (<10 IU/mL).	at delivery
Secondary	In utero HBV infection	HBV infection (SAg+, PCR positive)	at birth
Secondary	Maternal Adherence to TDF	HPLC measurement of serum	8 weeks after starting medication
Secondary	Maternal Adherence to TDF	HPLC measurement of serum	at delivery
Secondary	Infant Adherence to 3TC	HPLC measurement of serum	12 weeks after starting 3TC
Secondary	Infant Adherence to 3TC	HPLC measurement of serum	24 weeks after starting 3TC
Secondary	Hepatitis B Flare	Increase in ALT (>2x ULN) after stopping TDF at delivery	12 weeks after delivery
Secondary	Hepatitis B Flare	Increase in ALT (>2x ULN) after stopping TDF at delivery	24 weeks after delivery
Secondary	Preterm delivery	Delivery <37 weeks gestational age	assessed at delivery
Secondary	Composite Adverse Birth Outcomes	PTD, SAB, IUFD, neonatal death	during pregnancy or up to 28 days after delivery
Secondary	Incident HIV infection during pregnancy	Maternal HIV infection with seroconversion to positive test	at delivery
Secondary	Retention in Prenatal Care	at least 4 ANC visits after 28 weeks GA	assessed at time of delivery