Can BCG Vaccination at First Health-facility Contact Reduce Early Infant Mortality? A Cluster Randomised Trial
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 22,800
- 试验地点
- 1
- 主要终点
- Odds ratio of non-accidental early infant mortality
研究概览
简要总结
Bacillus Calmette-Guérin (BCG) vaccination is recommended at birth to protect against tuberculosis (TB) in countries with high TB burden. BCG is supplied in multidose vials with limited durability after reconstitution. In Guinea-Bissau, this has led to a practice of only opening a BCG vial at specific days, and only if sufficient children are present. Therefore, BCG vaccination is frequently delayed. Accumulating evidence indicates that BCG has beneficial effects on survival beyond the specific protection against tuberculosis, so called non-specific effects (NSEs).
The hypothesis of this study is that increasing the availability of BCG and vaccinating children at the first health-facility contact can reduce early infant non-accidental mortality by 25%.
In a cluster-randomised crossover trial, 23 health facilities (HFs) in three rural regions in Guinea-Bissau will be randomised to either continue with current practice (typically BCG vaccination once a week if a sufficient number of children are present for vaccination); or to offer additional BCG vaccines to make BCG available every day and open a vial of BCG if there is just one eligible child present. All children born in the three regions and registered during the study period, will be eligible for inclusion into the trial 1 day after birth. If consent is given by the mother, the child will be followed until day 42 after birth, when other vaccines are scheduled to be given. The primary outcome will be non-accidental mortality, secondary outcomes are non-accidental hospital admissions, non-accidental neonatal mortality and cost-effectiveness of making BCG available at the first health-facility contact.
详细描述
Background:
The World Health Organization (WHO) recommends Bacillus Calmette-Guérin (BCG) vaccination at birth to protect against TB in countries with high TB burden. Though the BCG vaccine is scheduled at birth, the vaccine is often given with delay, also among children born in Health Facilities (HFs), where it should be possible to obtain the vaccine. In 2010 in rural Guinea-Bissau, only 38% of children received BCG within the first month of life. BCG is supplied in 20-dose vials and unused doses must be discarded 6 hours after reconstitution. This has led to a local practice of not opening a BCG vial unless sufficient eligible children are present for vaccination. Moreover, the HFs seek to assemble larger groups of children eligible for BCG at specific days. Our observations from the field indicate that even on these days, vials may not be opened if the number of children is too low. Similar practises have been demonstrated in other low-income countries, but this practice is not in line with WHO recommendations, which emphasise that multi-dose vials should be opened and used to vaccinate one child despite any wastage.
In 2012, an estimated 73% of all neonatal deaths occurred within the first week of life. Several studies have suggested that BCG vaccination is associated with survival benefits early in life: In three randomised trials from Guinea-Bissau, BCG-at-birth was associated with a 38% lower neonatal mortality and marked reductions already 3 days after vaccination. A WHO-commissioned review and meta-analysis conducted in 2014 including five clinical trials indicated that BCG-vaccinated children had a relative risk of mortality at 0.70 (95% confidence interval 0.49-1.01) compared with BCG-unvaccinated children. Two randomised trials from India, both published after the review was conducted, found no effect of BCG at birth on neonatal mortality. In both India and Guinea-Bissau, all trials were conducted among low birth weight (LBW) children and primary outcome was neonatal mortality. In Guinea-Bissau, BCG-Denmark was used in all trials, whereas BCG-Russia was used in the trials from India. Strain of BCG has been suggested as a possible reason for the discrepancy between the trials in India, and the trials in Guinea-Bissau.
Therefore, early BCG vaccination may be important, not only for protection against tuberculosis, but also for the impact on survival.
Hypothesis:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 至 42 Days（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All children registered during pregnancy in Oio, Biombo or Farim by CHWs or the BHP HDSS
排除标准
- •Children, who have died within 1 day after birth
- •Children born outside Oio, Biombo and Farim health regions
研究组 & 干预措施
BCG available at first health facility contact
Infants living in catchment areas of HFs randomized to opening of BCG vial if just 1 eligible child is present.
干预措施: BCG vaccination at first health facility contact (Drug)
Usual availability of BCG at health facilities
Infants living in catchment areas of HFs randomized to BCG availability according to the per usual restricted vial opening policy aiming at reducing vaccine wastage. This entails that BCG vaccination is commonly only available on specific predefined days where a BCG vial will only be opened if several children are present.
结局指标
主要结局
Odds ratio of non-accidental early infant mortality
时间窗: From 1 day after birth to 42 days after birth
The primary analysis of early infant non-accidental mortality will be assessed in an intention-to-treat (TT) analysis. Logistic regression models with generalised estimating equation (GEE) correction for village cluster will be used. Furthermore, an assessment of whether the effect of the intervention on the primary outcome is modified by the following potential effect modifiers, will be carried out: Sex, maternal BCG scar (yes/no), season of birth (dry/rainy), strain of BCG.
次要结局
- Odds ratio of severe morbidity(From 1 day after birth to 42 days after birth)
- Odds ratio of non-accidental neonatal mortality(From 1 day after birth to 28 days after birth)
- Incremental cost-effectiveness ratio per death averted by making BCG available at the first health facility contact(From 1 day after birth to 42 days after birth)