Evaluating the Non-specific Effects of Different BCG Strains in Guinea-Bissau: Randomized Trial of the Impact on Early-life Hospital Admissions and Deaths
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 17,505
- 试验地点
- 2
- 主要终点
- Hospital admission at National Hospital Simão Mendes Pediatric Ward
研究概览
简要总结
Background: Investigators at Bandim Health Project (BHP, www.bandim.org) in Guinea-Bissau have shown in several randomized trials that the Bacille-Calmette-Guérin (BCG) vaccine against tuberculosis (TB) is associated with reduced mortality in the first months of life.
BCG is a live attenuated vaccine, which means that it consists of active tuberculosis bacteria that are not capable of infecting a human with TB. BCG has been grown and maintained at many different laboratories all over the world using slightly different laboratory techniques. Due to the accumulation of genetic mutations in the different BCG strains, many variants of the vaccine exists today. These have different properties when it comes to immune response, side effects, protection against TB and scar formation. The BCG scar status after vaccination is a good marker for the non-specific effects of the vaccine; among BCG-vaccinated infants, those with a BCG scar have improved survival. The investigators hypothesize that the different types of BCG vary in terms of the strength of the non-specific effects and thus the impact on overall morbidity and mortality.
In the trial, the investigators will compare the two most widely used BCG strains in the world, BCG-Russia and BCG-Japan, with respect to their non-specific effects on morbidity and mortality. As an addition, the investigators will study the effect of maternal BCG vaccination on the subsequent effect of BCG-vaccination in the offspring, since there are indications that the maternal BCG scar status primes for a stronger non-specific response in the offspring.
详细描述
In the trial, the investigators will compare the two currently most widely used BCG strains in the world, BCG-Russia and BCG-Japan, with respect to their non-specific effects on morbidity and mortality.
The investigators propose a 3-year randomized controlled trial (RCT) at the maternity ward of the main hospital Simão Mendes (HNSM) in urban Bissau, Guinea-Bissau, comparing 1:1 BCG-Japan vs. BCG-Russia in 15,600 infants with respect to morbidity and mortality. Additionally, the investigators will use this large study to test the role of the mother's BCG scar status for the overall health effect of BCG in her child.
Objective
The investigators aim to investigate the following hypotheses:
- Compared with BCG-Russia, vaccination with BCG-Japan is associated with fewer admissions and deaths.
- The effect of BCG in the child is more beneficial if the mother has a BCG scar.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- — 至 42 Days（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Newborn, unvaccinated infants identified at the maternity ward and ready to be discharged
排除标准
- •Infants above 6 weeks (>42 days) of age; Infants with gross malformation; Infants that are acutely ill
研究组 & 干预措施
BCG-RUSSIA
BCG-RUSSIA Infants randomised to receive BCG-RUSSIA at discharge from the Maternity Ward will receive one 0.05 ml dose Mycobacterium bovis BCG live attenuated vaccine BCG-RUSSIA (Serum Institute of India, Pune, India) by intradermal injection in the left deltoid region.
干预措施: BCG-Russia (Biological)
BCG-JAPAN
Infants randomised to receive BCG-JAPAN at discharge from the Maternity Ward will receive one 0.05 ml dose of Mycobacterium bovis BCG live attenuated BCG-JAPAN vaccine (Japan BCG Laboratory, Tokyo, Japan) by intradermal injection in the left deltoid region.
干预措施: BCG-Japan (Biological)
结局指标
主要结局
Hospital admission at National Hospital Simão Mendes Pediatric Ward
时间窗: 6 weeks
Number of participants admitted to the Pediatric Ward of National Hospital Simão Mendes within up to 6 weeks (42 days) of age. BHP documents all admissions at the ward.
次要结局
- Mortality, stratified by parental BCG scar status(6 months)
- Mortality(6 months)
- In-hospital case-fatality rate at National Hospital Simão Mendes Pediatric Ward(6 weeks)
- In-hospital case-fatality rate at Pediatric Ward(6 months)
- Hospital admission at National Hospital Simão Mendes Pediatric Ward(6 months)
- In-hospital case-fatality rate at National Hospital Simão Mendes' Pediatric Ward, stratified by parental BCG scar status(6 months)
- Hospital admission at National Hospital Simão Mendes' Pediatric Ward, stratified by parental BCG scar status(6 months)
- Mortality(6 weeks)
- Mortality, stratified by parental BCG scar status(6 weeks)
- Hospital admission at National Hospital Simão Mendes' Pediatric Ward, stratified by parental BCG scar status(6 weeks)
- In-hospital case-fatality rate at National Hospital Simão Mendes' Pediatric Ward, stratified by parental BCG scar status(6 weeks)