Clinical trial NCT05705427: The COMBAT HBV Feasibility Trial
Official title: Simplifying Hepatitis B Care in Pregnancy by Combining Birth-dose Vaccine and Tenofovir: The COMBAT HBV Feasibility Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hepatitis B
Vertical Transmission of Infectious Disease
Keywords: Prevention of mother-to-child transmission
Hepatitis B birth-dose vaccine
Tenofovir disoproxil fumarate
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Doris Duke Charitable Foundation
name: Université Protestant au Congo
name: Abbott
name: Albert Einstein College of Medicine
First posted: 2023-01-30
Enrollment: 560
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pregnant women will be randomized at the time of enrollment (at 28-32 weeks' gestation) in a 1:1 ratio to receive tenofovir disoproxil fumarate (TDF) vs placebo, with an expected 140 women in the TDF arm and 140 in the placebo arm. A permuted block randomization technique will be employed to ensure equal distribution between the two arms at the two maternity centers. A biostatistician from the University of North Carolina (UNC) will design the randomization scheme, which will utilize the randomization-and-concealment feature within the REDCap database; the biostatistician will not be directly involved in study enrollment activities. REDCap personnel at UNC will ensure proper design and use of the randomization-and-concealment feature, and study personnel will receive training on the randomization process prior to study roll-out.
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety (Pregnant Women): Number of Pregnant Women With Adverse Effects Related to Study Medications
timeFrame: Up to study close-out visit, or up to 12 months
measure: Safety (Infants): Number of Infants with Adverse Effects Related to Study Medications
timeFrame: At delivery
measure: Feasibility (Recruitment): Number of Eligible Participants Who Were Enrolled in the Study
timeFrame: Up to study close-out visit, or up to 12 months
measure: Feasibility (Refusal): Number of Eligible Participants Who Refused to Enroll in the Study
timeFrame: Up to study close-out visit, or up to 12 months
measure: Feasibility (Withdrawal): Number of Enrolled Participants Who Withdraw from the Study
timeFrame: Up to study close-out visit, or up to 12 months
measure: Feasibility (Retention): Number of Enrolled Participants Who Remain in the Study Through 6 Months Postpartum
timeFrame: Up to study close-out visit, or up to 12 months
measure: Feasibility (Maintenance): Proportion of Study Visits Completed Per Participant
timeFrame: Up to study close-out visit (12 months)
measure: Acceptability (Lab Testing): Number of Mothers With Lab Testing Acceptability Scores >80%
timeFrame: Upon study close-out visit, or up to 12 months
measure: Acceptability (Medication): Number of Mothers With Medication Acceptability Scores >80%
timeFrame: Upon study close-out visit, or up to 12 months
measure: 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
timeFrame: Measured at 6 months after birth
Secondary outcomes:
measure: Sensitivity of the Hepatitis B Core-Related Antigen Test
timeFrame: Measured at Enrollment
measure: Specificity of the Hepatitis B Core-Related Antigen Test
timeFrame: Measured at Enrollment
Other outcomes:
Locations:
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Université Protestant au Congo
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Peyton Thompson, MD, MSCR
role: PRINCIPAL_INVESTIGATOR
References: