The COMBAT HBV Feasibility Trial (COMBAT-HBV)

Simplifying Hepatitis B Care in Pregnancy by Combining Birth-dose Vaccine and Tenofovir: The COMBAT HBV Feasibility Trial

This is a double-blind, randomized placebo-controlled trial (RCT) of a prophylaxis-for-all approach to prevention of mother-to-child transmission (PMTCT) of hepatitis B virus (HBV) in the Democratic Republic of Congo (DRC). HBV-infected pregnant women will be randomized to either receive tenofovir or placebo beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum. Women will be followed every 4-6 weeks throughout the prenatal and postpartum period to evaluate for side effects related to the medication. Infants will receive a birth-dose of HBV vaccine, ideally within 24 hours. Participants will be followed longitudinally through 6 months' postpartum.

Study Overview

• Status: Completed
• Conditions: Hepatitis B; Vertical Transmission of Infectious Disease
• Intervention / Treatment: Biological: Hepatitis B monovalent vaccine; Drug: Tenofovir Disoproxil Fumarate 300 MG; Drug: Placebo

Detailed Description

The overall study design is a randomized, double-blind, placebo-controlled trial among two groups of mother-infant dyads: women who receive TDF vs placebo in late pregnancy and the postpartum period (beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum). While official World Health Organization (WHO) recommendations are to continue TDF at least through delivery, a range from delivery through 12 weeks' postpartum is possible; the investigators will continue therapy through 4 weeks' postpartum in this study. This feasibility trial will evaluate the acceptability, safety and preliminary effectiveness of a TDF-for-all approach to prevent MTCT of HBV in low-resource settings. HBsAg-positive pregnant women will be enrolled at 28-32 weeks' gestation, and will present for regular medication checks, with a study closeout visit at 24 weeks' postpartum. Study activities at monthly medication checks will include medication refills, assessment of adherence (via pill counts and verbal surveys), and evaluation for side effects. All infants will receive a birth-dose of HBV vaccine within 24 hours of life. MTCT of HBV will be defined as the proportion of infants with positive HBsAg testing at 6 months. This pilot study will provide preliminary data for sample size calculations, including safety and effectiveness data, to prepare for larger RCTs to determine the effectiveness of a tenofovir-for-all approach, as well as the added benefit of tenofovir over birth-dose vaccination.

• Study Type: Interventional
• Enrollment (Actual): 317
• Phase: Phase 4

Contacts and Locations

Study Locations

• Democratic Republic of the Congo
  • Kinshasa, Democratic Republic of the Congo
    • Université Protestant au Congo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant women ≥18 years of age who present for routine prenatal care between 28-32 weeks' gestation and who test HBV-positive by point-of-care hepatitis B surface antigen test. Women must intend to seek maternity and postpartum care exclusively at one of the Kinshasa-based study maternity centers.
• Infants born to enrolled women will be included in the study

Exclusion Criteria:

• Individuals with abnormal creatinine by point-of-care testing
• Any woman who plans to move outside of Kinshasa Province during the study period.
• Any HIV-positive individual, determined by routine point-of-care screening at antenatal care visits

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tenofovir disoproxil fumarate (TDF) arm; 140 pregnant women in the experimental arm will receive tenofovir disoproxil fumarate (TDF) 300 milligrams (mg) daily, beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum. Infants born to these women will be included in this arm and will receive a birth-dose of hepatitis B vaccine.	Biological: Hepatitis B monovalent vaccine; All infants born to women in the study will receive a birth-dose hepatitis B vaccine.; Other Names: Engerix-B; Hepatitis B birth-dose vaccine; Drug: Tenofovir Disoproxil Fumarate 300 MG; Pregnant women in the experimental arm will receive TDF daily beginning in the 3rd trimester of pregnancy and continuing through 1 month postpartum.; Other Names: Viread
Placebo Comparator: Placebo arm; 140 pregnant women in the placebo arm will receive a placebo pill daily, beginning at 28-32 weeks' gestation and continuing through 4 weeks' postpartum. Infants born to these women will be included in this arm and will receive a birth-dose of hepatitis B vaccine.	Biological: Hepatitis B monovalent vaccine; All infants born to women in the study will receive a birth-dose hepatitis B vaccine.; Other Names: Engerix-B; Hepatitis B birth-dose vaccine; Drug: Placebo; Pregnant women in the placebo arm will receive a placebo pill daily beginning in the 3rd trimester of pregnancy and continuing through 1 month postpartum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (Pregnant Women): Number of Pregnant Women With Adverse Effects Related to Study Medications	Safety of TDF prophylaxis in pregnant women, defined as a composite of adverse events (# mild adverse events [AEs], # moderate-to-severe AEs), presence of side effects and alanine aminotransferase elevations ≥ 5x upper limit of normal	Up to study close-out visit, or up to 12 months
Safety (Infants): Number of Infants with Adverse Effects Related to Study Medications	Safety of maternal TDF for infants, defined as a composite of: Birth weight (grams), mid-upper arm circumference (centimeters), gestational age at delivery (weeks and days), delivery mode (vaginal vs C-section), APGAR scores (0-10), # of adverse events	At delivery
Feasibility (Recruitment): Number of Eligible Participants Who Were Enrolled in the Study	Recruitment is indicative of the number of pregnant women who are screened versus those actually enrolled in the study.	Up to study close-out visit, or up to 12 months
Feasibility (Refusal): Number of Eligible Participants Who Refused to Enroll in the Study	Refusal will be defined as the number of individuals who refuse enrollment upon initial recruitment.	Up to study close-out visit, or up to 12 months
Feasibility (Withdrawal): Number of Enrolled Participants Who Withdraw from the Study	Withdrawal is indicative of the number of enrolled participants who choose not to continue study activities after having been enrolled.	Up to study close-out visit, or up to 12 months
Feasibility (Retention): Number of Enrolled Participants Who Remain in the Study Through 6 Months Postpartum	Retention is defined as the number of participants who remain in the study through the 6-month postpartum visit.	Up to study close-out visit, or up to 12 months
Feasibility (Maintenance): Proportion of Study Visits Completed Per Participant	Adherence to study visits and procedures, defined as proportion of the actual number of visits attended divided by the expected study visits (8) and multiplied by 100.	Up to study close-out visit (12 months)
Acceptability (Lab Testing): Number of Mothers With Lab Testing Acceptability Scores >80%	Number of mothers who report the process of undergoing lab draws as "acceptable" in the exit survey. Range 0-100%, with 0% being unacceptable and 100% being acceptable.	Upon study close-out visit, or up to 12 months
Acceptability (Medication): Number of Mothers With Medication Acceptability Scores >80%	Number of mothers who report the process of taking the study medication as "acceptable" in the exit survey. Range 0-100%, with 0% being unacceptable and 100% being acceptable.	Upon study close-out visit, or up to 12 months
Preliminary Effectiveness: Number of Infants With HBV Positivity by Rapid Diagnostic Testing at 6 Months of Life to Indicate Mother-to-Child Transmission of HBV	Mother-to-child transmission of HBV is defined as HBsAg positivity in the infant at 6 months of life.	Measured at 6 months after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of the Hepatitis B Core-Related Antigen Test	Sensitivity will be defined as the number of true positive tests divided by the sum of the true positives and false negatives.	Measured at Enrollment
Specificity of the Hepatitis B Core-Related Antigen Test	Specificity will be defined as the number of true negative tests divided by the sum of the true negatives and the false positives.	Measured at Enrollment

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Albert Einstein College of Medicine; Abbott; Doris Duke Charitable Foundation; Université Protestant au Congo
• Investigators: Principal Investigator: Peyton Thompson, MD, MSCR, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2023
• Primary Completion (Actual): November 25, 2025
• Study Completion (Actual): November 25, 2025

Study Registration Dates

• First Submitted: January 20, 2023
• First Submitted That Met QC Criteria: January 20, 2023
• First Posted (Actual): January 30, 2023

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Tenofovir disoproxil fumarate; Prevention of mother-to-child transmission; Hepatitis B birth-dose vaccine
• Additional Relevant MeSH Terms: Blood-Borne Infections; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis; Hepatitis B; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Purines; Organophosphorus Compounds; Organophosphonates; Adenine; Tenofovir; Engerix-B
• Other Study ID Numbers: 22-1492

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Datasets will not be made publicly available because they contain protected health information. However, the authors will share de-identified participant data, alongside the study protocol, statistical analysis plan, and analytic code, upon reasonable request and with approval by an independent review committee (ie, learned intermediary). An executed Data Use/Sharing agreement with the University of North Carolina at Chapel Hill (UNC-CH) is required before data will be shared
• IPD Sharing Time Frame: Data will be available from 9 to 36 months after publication.
• IPD Sharing Access Criteria: Interested individuals can request de-identified data with approval from an independent review committee, which will be shared upon execution of a Data Use/Sharing Agreement with UNC-CH.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes