Reducing Vertical Transmission of Hepatitis B in Africa (REVERT-B)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis B Infection
• Intervention / Treatment: Drug: Tenofovir Disoproxil Fumarate; Drug: Lamivudine Oral Solution

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.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jodie Dionne, MD, MSPH; Phone Number: 2059756530; Email: jdionne@uabmc.edu
• Study Contact Backup: Name: Jamie White; Phone Number: 2059348145; Email: jcarleen@uab.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama At Birmingham
      • Contact: Jodie Dionne-Odom; Phone Number: 205-975-6530; Email: jdionne@uabmc.edu
      • Principal Investigator: Jodie A Dionne-Odom, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pregnant Women - Tenofovir; 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.	Drug: Tenofovir Disoproxil Fumarate; oral TDF medication 300 mg daily; Other Names: TDF
Placebo Comparator: Newborn Infants - Lamivudine; 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.	Drug: Lamivudine Oral Solution; Oral lamivudine with weight-based dosing BID from birth until 6 months of age; Other Names: 3TC

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In utero HBV infection	HBV infection (SAg+, PCR positive)	at birth
Maternal Adherence to TDF	HPLC measurement of serum	8 weeks after starting medication
Maternal Adherence to TDF	HPLC measurement of serum	at delivery
Infant Adherence to 3TC	HPLC measurement of serum	12 weeks after starting 3TC
Infant Adherence to 3TC	HPLC measurement of serum	24 weeks after starting 3TC
Hepatitis B Flare	Increase in ALT (>2x ULN) after stopping TDF at delivery	12 weeks after delivery
Hepatitis B Flare	Increase in ALT (>2x ULN) after stopping TDF at delivery	24 weeks after delivery
Preterm delivery	Delivery <37 weeks gestational age	assessed at delivery
Composite Adverse Birth Outcomes	PTD, SAB, IUFD, neonatal death	during pregnancy or up to 28 days after delivery
Incident HIV infection during pregnancy	Maternal HIV infection with seroconversion to positive test	at delivery
Retention in Prenatal Care	at least 4 ANC visits after 28 weeks GA	assessed at time of delivery

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Jodie Dionne, MD, MSPH, University of Alabama At Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 7, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: perinatal infection, hepatitis B in pregnancy
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Lamivudine
• Other Study ID Numbers: IRB-300006586; 5R01HD101545 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No