The COMBAT HBV Feasibility Trial (COMBAT-HBV)

University of North Carolina (UNC)

Status and phase: Enrolling; Phase 4

Conditions: Hepatitis B; Vertical Transmission of Infectious Disease

Treatments: Drug: Placebo; Biological: Hepatitis B monovalent vaccine; Drug: Tenofovir Disoproxil Fumarate 300 MG

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05705427

22-1492

Details and patient eligibility

About

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.

Full 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.

Enrollment: 560 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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560 participants in 2 patient groups, including a placebo group

Tenofovir disoproxil fumarate (TDF) arm

Experimental group

Description:

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.

Treatment:

Drug: Tenofovir Disoproxil Fumarate 300 MG

Biological: Hepatitis B monovalent vaccine

Placebo arm

Placebo Comparator group

Description:

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.

Treatment:

Biological: Hepatitis B monovalent vaccine

Drug: Placebo