"HBV unIversal vs Point-Of-Care-based Antiviral treatMent to Prevent Mother-to-child Transmission"
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 3,200
- 主要终点
- Percentage of HBsAg-positive women with HBV DNA <200,000 IU/mL at the time of delivery
研究概览
简要总结
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.
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •≥18 years old, or ≥ the legal age of majority as defined by each country, on the day of inclusion.
- •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
- •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.
排除标准
- •HIV co-infection.
- •HBV treatment ongoing on the day of inclusion.
- •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.
- •Severe gravid disease at inclusion, which poses a life-threatening risk to the mother and/or child
- •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).
研究组 & 干预措施
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.
干预措施: HBsAg RDT Women (Diagnostic Test)
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.
干预措施: Treatment by TDF (Drug)
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.
干预措施: Social sciences component (Other)
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.
干预措施: HBsAg RDT Infants (Diagnostic Test)
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.
干预措施: HBsAg RDT Women (Diagnostic Test)
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.
干预措施: Treatment by TDF if HBcrAg RDT positive (Drug)
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.
干预措施: Social sciences component (Other)
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.
干预措施: HBsAg RDT Infants (Diagnostic Test)
结局指标
主要结局
Percentage of HBsAg-positive women with HBV DNA <200,000 IU/mL at the time of delivery
时间窗: 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.
次要结局
- Percentage of infants positive for HBsAg(At 9 months of life)