A Prospective Study to Evaluate the Safety, Effectiveness and Impact of the RTS, S/AS01E Vaccine in Young Children in Sub-Saharan Africa
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 77,953
- 试验地点
- 6
- 主要终点
- Incidence rates of aetiology-confirmed meningitis
研究概览
简要总结
The RTS, S/AS01E vaccine was developed to protect children in sub-Saharan Africa from malaria as part of routine immunization programs. This study aims to check the vaccine's safety after it has been introduced. Along with safety, researchers will also assess how well the vaccine works and its overall impact on children's health.
详细描述
This is a disease surveillance study with prospective cohort event monitoring including both temporal and concurrent comparisons of the occurrence of adverse and malaria events between vaccinated and unvaccinated subjects living in exposed or unexposed clusters located in sub-Saharan Africa (SSA) countries, and eligible for RTS,S/AS01E vaccination for those living in the exposed clusters. The design includes active surveillance and enhanced hospitalization surveillance in both exposed and unexposed clusters.
The study targeted enrolling at least 45,000 children in active surveillance, including 22,500 in the exposed clusters and 22,500 in the unexposed clusters for evaluation of the vaccine safety, effectiveness, and impact.
All data analyses will be computed in a descriptive manner. Data regarding the hospitalization will be uniformly collected whether the child is enrolled in active surveillance or in enhanced hospitalization surveillance.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All study participants must satisfy ALL the following criteria at study entry:
- •Study participants' parent(s)/ LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
- •Written informed consent provided from either the parent(s) or LAR of the study participant.
- •Study participant living in the HDSS or equivalent surveillance system area.
- •For enrolment in the active surveillance - DTP group: children must be aged less than (<) 18 months, identified at any administration of DTP/HepB/Hib (or at hospitalisation before 3rd dose of DTP/HepB/Hib in case of hospitalisation and vaccinated with at least one dose of DTP/HepB/Hib). (This group will include children from exposed and unexposed clusters.) OR For enrolment in the active surveillance - Catch-up group: children must be aged <18 months, received at least one dose of DTP/HepB/Hib vaccine, whose age corresponds to the age after the 3rd dose of DTP/HepB/Hib vaccine, (=who either received all DTP/HepB/Hib doses before study start or received at least one dose of DTP/HepB/Hib and are older than the age corresponding to the 3rd DTP/HepB/Hib dose at study start) and identified at 1st RTS,S/AS01E dose administration (This group will include children from exposed clusters only).
- •OR For enrolment in the enhanced hospitalisation surveillance: children must be aged at least 6 weeks and <5 years at the time of hospitalisation at any time during the study. (This group will include children from exposed and unexposed clusters.) Parents/LARs of children meeting all eligibility criteria for active surveillance, not having completed the visits for DTP/HepB/Hib, and first identified during hospitalisation, must first be proposed enrolment in active surveillance (if recruitment is not completed).
- •Children already enrolled in active surveillance will have hospitalization monitored as part of the procedures related to the active surveillance and can therefore not be enrolled in enhanced hospitalization surveillance.
排除标准
- •Child in care = A child who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government, or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a child in care can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a child in care does not include a child who is adopted or has an appointed legal guardian.
研究组 & 干预措施
Active surveillance (DTP sub-Group)
Children enrolled in the active surveillance (AS), <18 months of age who were identified at any administration of DTP/HepB/Hib (usually given at 6, 10 and 14 weeks of age) or at hospitalisation before administration of 3rd dose of DTP/HepB/Hib and vaccinated with at least one dose of DTP/HepB/Hib; including both RTS,S/AS01E vaccinated and unvaccinated children (from exposed or unexposed clusters), living in the HDSS area are eligible for enrolment in the DTP sub-group of active surveillance.
干预措施: Whole blood sample (Procedure)
Active surveillance (Catch-up sub-Group)
Children enrolled in the active surveillance (AS), <18 months of age who were identified at 1st RTS,S/AS01E dose administration and who either received all DTP/HepB/Hib doses before study start or received at least one dose of DTP/HepB/Hib and are older than the age corresponding to the 3rd DTP/HepB/Hib dose at study start; including only RTS,S/AS01E vaccinated children from exposed clusters who could not be recruited at the time of DTP/HepB/Hib administration because the study had not yet started, living in the HDSS area are eligible for enrolment in the Catch-up sub-group of active surveillance.
干预措施: Whole blood sample (Procedure)
Enhanced Hospitalisation Surveillance Group
Children at least 6 weeks and <5 years of age, within the study areas in both exposed and unexposed clusters, not already enrolled in the active surveillance (because parents/ Legally Acceptable Representative (LARs) declined enrolment in active surveillance or because recruitment had been completed) or not eligible for active surveillance at the time of hospitalisation, living in the HDSS area are eligible for enrolment in the Enhanced Hospital Surveillance (EHS) group.
干预措施: Whole blood sample (Procedure)
结局指标
主要结局
Incidence rates of aetiology-confirmed meningitis
时间窗: During the entire study period (From Day 0 up to Month 62)
Incidence rate of aetiology confirmed meningitis is analyzed with an at-risk period of 12 months. At the site level, a suspected meningitis case based on clinical symptoms and/or signs is defined as: * A child with sudden onset of fever (\> 38.0°C rectal or 37.5°C axillary) and one or more of the following signs: neck stiffness, altered consciousness with no other alternative diagnosis, or other meningeal sign such as bulging fontanelle in children under one year of age. If a Cerebrospinal fluid (CSF) sample is available and any known aetiologic agent (bacterial or not) has been identified, it is defined as an aetiology confirmed meningitis. The incidence rate will be calculated by dividing the number of study participants reporting at least one event over the follow-up period by the total person-time.
Incidence rates of adverse events of special interest (AESI)
时间窗: During the entire study period (From Day 0 up to Month 62)
AESI are predefined list of adverse events that have historically been associated with vaccines other than RTS,S/AS01E, or may hypothetically be associated with RTS,S/AS01E due to the fact that this vaccine has components which are new compared to current widely used vaccines. The incidence rate will be calculated by dividing the number of study participants reporting at least one event over the follow-up period by the total person-time. The person-time for an event of interest will be calculated as the time between the reference date (date of first RTS,S/AS01E vaccination for the vaccinated study participants and virtual vaccination corresponding to the week before first visit for the unvaccinated study participants) and the end of the at-risk period or the earliest of the followings: Date of first diagnosis of event of interest, Date of end of study period, Date when child reaches 5 years, Date of last contact or Date of death.
次要结局
- Incidence rate of probable meningitis (final classification)(During the entire study period (From Day 0 up to Month 62))
- Incidence rates of clinically suspected meningitis (final classification)(During the entire study period (From Day 0 up to Month 62))
- Number of meningitis cases identified at site level (first line laboratory)(During the entire study period (From Day 0 up to Month 62))
- Incidence rates of cerebral malaria (diagnosed by Rapid Diagnostic Test [RDT] and/or microscopy)(During the entire study period (From Day 0 up to Month 62))
- Incidence rates of malaria episodes diagnosed by RDT and/or microscopy(During the entire study period (From Day 0 up to Month 62))
- Incidence rates of anaemia cases at hospital entry among hospitalised children(During the entire study period (From Day 0 up to Month 62))
- Incidence rates of hospitalisation cases(During the entire study period (From Day 0 up to month 62))
- Number of deaths(During the entire study period (From Day 0 up to month 62))