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

NCT ID: NCT07054359

Last Updated: 2025-07-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 3200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-30
• Study Completion Date: 2028-01-31

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.

Detailed Description

I) Methodology and Study Design

The study combines two components:

I. Core Research Study Study Design Two-Arm Parallel, Cluster-Randomized Trial Design, Open-Label, Non-Inferiority Trial 1:1 Allocation Ratio 1:1 Arm 1: Intervention Group (Selective Strategy) HBsAg-positive women → Tested for HBcrAg RDT → TDF treatment if HBcrAg positive.

Arm 2: Control Group (Universal Strategy) HBsAg-positive women → Immediate TDF treatment

Clusters Randomization unit: Primary Health Centers (PHCs) or rural hospitals Total clusters: 80 (40 per group, 16 clusters per country)

Participants Total participants: 3200 HBsAg-positive women 1600 women per group → 640 women per country → 40 per cluster

Key eligibility criteria for clusters include:

• Rural or semi-rural location.
• No involvement in similar strategies
• No routine HBV DNA or HBeAg testing.
• Enough antenatal care visits to reach the target of 40 HBsAg-positive women in one year
• At least two nurses or midwives.
• HBV vaccination program in place
• Motivation to participate.

II. The Social Science component:

The social sciences component of the study will be conducted in only 2 countries (Cambodia and Ivory Coast) and includes three key sub-studies:

• The socio-economic and behavioral study aims to assess i) the acceptability of the two strategies by the healthcare workers involved in implementing the trial in the study sites and by the pregnant women who will participate in the trial and benefit from HBV PMTCT interventions, ii) the impacts of the strategies on health literacy, HBV knowledge, perceived health, treatment adherence and retention into care, iii) women experience related to HBV status disclosure and perceptions on HBV partner and children screening
• The health economic evaluation will analyze the strategies' costs, benefits, and cost-effectiveness, considering health and cost outcomes over the study period and the long term.
• The health policy study will evaluate the feasibility and sustainability of the strategies at the institutional level and explore political, institutional, and social factors that influence integrating the study results into national health policies.

A mixed-methods approach will be used, including qualitative interviews and quantitative questionnaires among pregnant women and healthcare workers.

Additionally, a qualitative assessment of the two strategies' acceptability, alongside a health policy analysis, will be conducted in Togo to enrich the study's contextual understanding. This initiative will also enhance the partner team's social science research capacity through targeted training and skill development in qualitative research for students and early-career researchers.

II) Intervention:

Medication: Tenofovir Disoproxil Fumarate (TDF); Administration Route: Oral Dosage: 300 mg/day or 300 mg every 2 days (if creatinine clearance is 30-50 ml/min)

Preventive treatment:

• Initiated during inclusion visit (if eligible for treatment in group 1, and for all in group 2)
• Continued until the 6-8 weeks postpartum visit Post-partum assessment and treatment At 3-month postpartum, all HBsAg-positive women will undergo a liver disease assessment at the closest district or provincial hospital. This assessment will include HBV DNA, HBeAg, HBcrAg-RDT, ALT/AST, platelet count, and liver ultrasound. Criteria for resuming treatment will follow the 2024 WHO guidelines. In case of TDF resumption, the treatment will be funded by the trial for 6 months, and the woman will be followed at a district or provincial hospital

III) Statistical methods

Core research study. The investigators predict that with the universal strategy, the proportion of women meeting the primary endpoint would be 78%. They chose a non-inferiority margin of 10% when comparing the HBcrAg-RDT strategy to the universal strategy. This indicates that a 68% success rate would be accepted for the same primary endpoint under the worst-case HBcrAg-RDT strategy.

They plan to recruit 40 HBsAg-positive women in each PHC. With a coefficient of variation between clusters of 0.143, derived from the assumptions, the trial requires 40 clusters per group, totaling 80 clusters of 40 HBsAg-positive women each, for 90% power at two-sided 5% (2.5% one-sided) significance to show non-inferiority within a margin of 10%.

Social Science quantitative data:

The sample size for the social science data is based on the proportion of women with good knowledge of hepatitis B, 90% power, two-sided 5% significance, and 20% loss to follow-up at the 9-month postpartum visit. Assuming 23% and 29% of women having good knowledge of hepatitis B at inclusion and the 9-month postpartum visit, respectively, overall for both strategies, with a correlation coefficient before-after of 0.15, 32 clusters (16 per country) of 40 women each (totaling 1280 participants) will be needed to show significant differences in the proportion of women with good knowledge of hepatitis B between inclusion and the 9-month postpartum visit (overall, considering both strategies together).

Conditions

HBV Infection; Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Universal strategy

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.

Group Type: OTHER

HBsAg RDT Women

Intervention Type: DIAGNOSTIC_TEST

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

Treatment by TDF

Intervention Type: DRUG

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

Social sciences component

Intervention Type: 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

HBsAg RDT Infants

Intervention Type: 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

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.

Group Type: EXPERIMENTAL

HBsAg RDT Women

Intervention Type: DIAGNOSTIC_TEST

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

Treatment by TDF if HBcrAg RDT positive

Intervention Type: DRUG

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

Social sciences component

Intervention Type: 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

HBsAg RDT Infants

Intervention Type: 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.

Interventions

HBsAg RDT Women

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

Intervention Type: DIAGNOSTIC_TEST

Treatment by TDF if HBcrAg RDT positive

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

Intervention Type: DRUG

Treatment by TDF

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

Intervention Type: DRUG

Social sciences component

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

Intervention Type: OTHER

HBsAg RDT Infants

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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

1. ≥18 years old, or ≥ the legal age of majority as defined by each country, on the day of inclusion.

2. Pregnancy.

3. Intention to attend antenatal care visits in the Primary Health Center or the Rural Hospital

4. Living in an area covered by the Primary Health Center or the Rural Hospital on the start date of the trial

5. Positive HBsAg identified during the screening phase of the study

6. Free, informed, and written consent, signed by the person and the investigator at the latest on the day of inclusion and before any examination carried out as part of the study.

Exclusion Criteria

1. HIV co-infection.

2. HBV treatment ongoing on the day of inclusion.

3. Having at least one of the following criteria indicatives of the third trimester of pregnancy:

• Gestational Age-Based Exclusion:

The reported gestational age is ≥28 weeks, based on the last menstrual period (LMP) if known.

• Ultrasound-Based Exclusion:

Fetal biometry (e.g., head circumference, femur length) on ultrasound suggests a gestational age of ≥28 weeks.

• Fundal Height-Based Exclusion:

Symphysis-fundal height (SFH) measurement of ≥ 28 cm which corresponds to approximately 28 weeks of gestation.

4. Severe gravid disease at inclusion, which poses a life-threatening risk to the mother and/or child

5. Any concomitant medical condition that, according to the clinical site investigator, would contraindicate participation in the study.

6. Concurrent participation in any other study (unless approved in writing by the Global Principal Investigators).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Olivier SEGERAL

Role: STUDY_DIRECTOR

University Hospital, Geneva

Central Contacts

Olivier SEGERAL

Role: CONTACT

olivier.segeral@hug.ch

+ 41 79 553 6535

Yusuke SHIMAKAWA

Role: CONTACT

yusuke.shimakawa@pasteur.fr

+33 (0)1 40 61 39 58

Other Identifiers

ANRS 0562s HIPOCAMP

Identifier Type: -

Identifier Source: org_study_id