"HBV unIversal vs Point-Of-Care-based Antiviral treatMent to Prevent Mother-to-child Transmission"

NCT07054359 | Not Yet Recruiting

• 1 other identifier: ANRS 0562s HIPOCAMP
• Study Type: interventional
• Target: 3,200
• Locations: 0 countries
• Sites: N/A

Brief Summary

To achieve global elimination of hepatitis B virus (HBV), it is crucial to eliminate HBV mother-to-child transmission (MTCT) by ensuring high coverage of birth dose vaccine and expanding the adoption of peripartum antiviral prophylaxis (PAP) by tenofovir. Current international guidelines require hepatitis B surface antigen (HBsAg)-positive pregnant women to undergo viral load (VL) quantification to identify those at high risk (VL ≥200,000 IU/mL) who should receive PAP. However, VL testing remains inaccessible in many low- and middle-income countries (LMICs), particularly in rural areas. Consequently, in the forthcoming guidelines, the WHO is going to issue a conditional recommendation for administering PAP to all HBsAg-positive women lacking access to VL testing. Although this universal strategy may appear promising for simplifying the diagnostic process, it may result in overtreating the majority of HBsAg-positive pregnant women, estimated at 85% in Africa and 70% in Asia, for whom birth dose vaccine is likely sufficient. Moreover, the real-world applicability of this strategy in LMICs has never been formally tested. As an innovative alternative, the adoption of a rapid point-of-care test for hepatitis B core-related antigen (HBcrAg-RDT) is proposed to identify women eligible for PAP.This test requires only a drop of capillary blood, eliminating the need for electricity or centrifugation, and can provide a reliable result within 45 minutes. Compared to the universal strategy, HBcrAg-RDT strategy is expected to be less expensive and could prevent unnecessary tenofovir exposure for both women and their fetuses. Our aim is to establish the non-inferiority of the HBcrAg-RDT strategy, in comparison to the universal strategy, in terms of effectiveness, defined as the reduction in maternal VL at the time of childbirth, a main driver of the MTCT risk. This will be approached through a multidisciplinary framework integrating health economics, implementation science, and health policy analysis.

Conditions

HBV Infection; Pregnancy

Keywords

Pregnancy; Mother to child transmission; Public health; Hepatitis B; Cluster-randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Percentage of HBsAg-positive women with HBV DNA <200,000 IU/mL at the time of delivery

  The primary endpoint will be the percentage of HBsAg-positive women who present at healthcare facilities for delivery and have an HBV DNA \<200,000 IU/mL at the time of delivery.

  Delivery

Secondary Outcomes (1)

• Percentage of infants positive for HBsAg

  At 9 months of life

Other Outcomes (17)

• Percentage of women eligible for PAP who started TDF

  At screening

• Percentage of women eligible for PAP who completed TDF prophylaxis

  up to 40 weeks of gestation

• Percentage of women with adherence >90% at each study visit based on pill counts and self-report

  from inclusion to delivery, max 40 weeks

Study Arms (2)

Universal strategy

OTHER

Pregnant women who test positive for HBsAg will initiate TDF preventive treatment on the same day of their visit. Their child/children will be enrolled in the study until 9 months.

Diagnostic Test: HBsAg RDT Women; Drug: Treatment by TDF; Other: Social sciences component; Diagnostic Test: HBsAg RDT Infants

Selective strategy

EXPERIMENTAL

Pregnant women who test positive for HBsAg will be tested for HBcrAg RDT on the same day of their visit, and those who test positive will initiate TDF preventive treatment on the same date.Their child/children will be enrolled in the study until 9 months.

Diagnostic Test: HBsAg RDT Women; Drug: Treatment by TDF if HBcrAg RDT positive; Other: Social sciences component; Diagnostic Test: HBsAg RDT Infants

Interventions

HBsAg RDT Women DIAGNOSTIC_TEST

HBsAg will be screened using finger-stick capillary blood during the ANC visit, simultaneously with the HIV test

Selective strategy; Universal strategy

Treatment by TDF if HBcrAg RDT positive DRUG

300mg per day or 300 mg every 2 days (if créatinine clearance is 30-50ml/min)

Selective strategy

Treatment by TDF DRUG

300mg per day or 300 mg every 2 days (if créatinine clearance is 30-50ml/min)

Universal strategy

Social sciences component OTHER

The social sciences component only in Cambodia and Ivory Coast. 3 key sub-studies: i) a socio-economic and behavioral study ii) a health economic evaluation study, and iii) a health policy study. A mixed-methods approach will be used, including qualitative interviews and quantitative questionnaires among pregnant women and healthcare workers

Selective strategy; Universal strategy

HBsAg RDT Infants DIAGNOSTIC_TEST

At 9 months, all infants will be tested for HBsAg; HBsAg-positive infants will undergo HBV DNA testing, and DBS will be collected for biobank storage.

Selective strategy; Universal strategy

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnancy.
• Intention to attend antenatal care visits in the Primary Health Center or the Rural Hospital
• Living in an area covered by the Primary Health Center or the Rural Hospital on the start date of the trial
• Positive HBsAg identified during the screening phase of the study

You may not qualify if:

• HIV co-infection.
• Having at least one of the following criteria indicatives of the third trimester of pregnancy:
• The reported gestational age is ≥28 weeks, based on the last menstrual period (LMP) if known.
• Fetal biometry (e.g., head circumference, femur length) on ultrasound suggests a gestational age of ≥28 weeks.
• Symphysis-fundal height (SFH) measurement of ≥ 28 cm which corresponds to approximately 28 weeks of gestation.
• Any concomitant medical condition that, according to the clinical site investigator, would contraindicate participation in the study.
• Concurrent participation in any other study (unless approved in writing by the Global Principal Investigators).

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

MeSH Terms

Conditions

Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Olivier SEGERAL

  University Hospital, Geneva

  STUDY DIRECTOR

Central Study Contacts

Olivier SEGERAL

CONTACT

+ 41 79 553 6535; olivier.segeral@hug.ch

Yusuke SHIMAKAWA

CONTACT

+33 (0)1 40 61 39 58; yusuke.shimakawa@pasteur.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: A two-arm parallel cluster-randomized, open-label, non-inferiority trial will be conducted in five countries across two regions: sub-Saharan Africa (Cameroon, Ivory Coast, Togo) and Asia (Cambodia, Vietnam). The randomization (cluster) unit will be a primary health center (PHC) or a rural hospital.

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: July 8, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): January 1, 2028
• Last Updated: July 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share