BCG2-DTP3: Providing BCG Revaccination With the Third Dose of Diphtheria-tetanus-pertussis Vaccine to Improve Female Survival in Africa
试验速览
- 阶段
- 4 期
- 状态
- Enrolling By Invitation
- 入组人数
- 6,000
- 试验地点
- 1
- 主要终点
- Non-accidental servere morbidity
研究概览
简要总结
Studies in low-income countries show that vaccines can have important non-specific effects on other infections. Live BCG vaccine can train the immune system and reduce susceptibility to unrelated infections. In contrast, non-live diphtheria-tetanus-pertussis-containing (DTP) vaccine enhances susceptibility in females: DTP vs no DTP is associated with 2-fold higher mortality, and in DTP-vaccinated children, females have higher mortality than males. These effects are seen as long as a vaccine is the most recent vaccine. WHO recommends BCG at birth followed by three DTP vaccines. A metaanalysis based on observational studies has shown that co-administration of BCG+DTP is associated with lower mortality than BCG followed by DTP.
The investigators will implement a randomised trial in urban Guinea-Bissau, including 6000 children, to test the hypothesis that an extra dose of BCG given with DTP3 (BCG2+DTP3 vs. DTP3) can:
- reduce death and hospital admissions by 25%
- reduce the F/M severe morbidity hazard ratio
详细描述
Background:
Since the 1970s, the basic vaccination schedule in low-income countries has sequenced BCG and DTP, so that BCG was provided at birth and diphtheria-tetanus-pertussis vaccine (DTP, now in a version with H. influenza vaccine and hepatitis B, 'pentavalent vaccine') in 3 doses at 6,10, and 14 weeks, followed by measles vaccine (MV) at 9 months of age.
WHO recommends DTP-after-BCG but a meta-analysis of observational studies has shown that co-administration of BCG+DTP is associated with 43% (27-54%) lower mortality than DTP after BCG (Higgins et al, BMJ 2016).
The idea that vaccines can change morbidity and mortality in ways not explained by prevention of the vaccine-targeted infection is gaining increasing recognition. Major examples of beneficial NSEs include that the live BCG vaccine reduces non-tuberculosis infections. In contrast, the non-live DTP vaccine is associated with increased susceptibility to non-DTP infections and higher female mortality.
When WHO reviewed the NSEs of vaccines, the DTP vaccine was associated with a 38% (-8-108%) increase in mortality, but providing BCG-with-DTP was associated with 48% (30-66%) lower mortality than the usual schedule of BCG-then-DTP.
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
- Single (Outcomes Assessor)
盲法说明
All follow-up will be masked as the intervention is not marked on the child's vaccination card.
入排标准
- 年龄范围
- 14 Weeks 至 24 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Children, who are between 14 weeks and 24 weeks of age,
- •Received DTP2 at least 4 weeks earlier and who are due to receive DTP3.
排除标准
- •Children, who are ill and require hospitalization.
- •Children with severe malformations
- •Children, who had suppurative lymphadenitis after BCG1 (extremely rare)
研究组 & 干预措施
BCG2+DTP3
Infants aged 14-24 weeks will receive a second dose of BCG with the third dose of DTP.
干预措施: BCG Vaccine (Biological)
结局指标
主要结局
Non-accidental servere morbidity
时间窗: Baseline to the age of measles vaccine (scheduled at 9 months, to be received by latest by 12 months. Children will be censored upon migration or death.
Composite outcome of death and admissions. Obtained via active follow-up of participants by phone calls, home visits and at the hospital. Cox regression models will be used to compare severe morbidity for BCG2+DTP3 versus controls (DTP3). The comparison of BCG2+DTP3 vs DTP3 will also be analysed separately by sex
次要结局
- Female/Male servere morbidity ratio(Baseline to the age of measles vaccine (scheduled at 9 months, to be received by latest by 12 months. Children will be censored upon migration or death.)
- Non-accidental mortality(Baseline to the age of measles vaccine (scheduled at 9 months, to be received by latest by 12 months. Children will be censored upon migration or death.)
- Cause-specific deaths(Baseline to the age of measles vaccine (scheduled at 9 months, to be received by latest by 12 months. Children will be censored upon migration or death.)
- Non-accidental morbidity(Baseline to the age of measles vaccine (scheduled at 9 months, to be received by latest by 12 months. Children will be censored upon migration or death.)
- Cause-specific admissions(Baseline to the age of measles vaccine (scheduled at 9 months, to be received by latest by 12 months. Children will be censored upon migration or death.)
- Consultations(Baseline to the age of measles vaccine (scheduled at 9 months, to be received by latest by 12 months. Children will be censored upon migration or death.)
- Adverse reactions in a subset of 800 participants(From baseline to baseline+6 months)