Determining Whether Mass Campaigns With Fractional Dose PCV10 Would Accelerate Herd Protection Against Pneumococcal Transmission in Sub-Saharan Africa
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Epicentre
- 入组人数
- 44,618
- 试验地点
- 1
- 主要终点
- Effect of a Single Dose PCV10 Campaign in the Reduction of VT Carriage
研究概览
简要总结
The aim of this study is to assess the impact of a mass campaign with a single, fractional dose of Pneumosil®, a PCV10, on VT carriage. A 20% fractional dose (1/5th) will be used as a practical formulation to prepare and administer. This study will assess whether the impact of a single fractional dose mass campaign on carriage is non-inferior to a single full dose mass campaign in a cluster randomized trial in a low coverage setting in Niger. The results would provide evidence of the population-level direct and indirect impact of fractional dose in older children which will be completed by mathematical modelling, to inform the policy debate regarding PCV dosing schedules in different contexts. This trial and the modelling exercises that follow, would allow for larger scale evaluation of fractional dose PCV strategies in multiple contexts.
详细描述
In 2015, there were an estimated 8.9 million cases (uncertainty range 7.7-10.6 million) of clinical pneumococcal pneumonia globally, with 2.4 million cases estimated in Africa alone (uncertainty range 2.1-3.1 million). These figures represent a global reduction of 37% from 14.2 million cases (12.3 million-16.9 million) in 2000. However, pneumococcal disease continues to be a leading cause of severe disease and death representing 10% of all death in children under 5 years of age (1). These deaths occur disproportionally in low- and middle-income countries (LMICs), with approximately 50% of global pneumococcal deaths estimated to occur in 4 countries: India, Nigeria, Pakistan and the Democratic Republic of Congo.
Vaccination campaigns targeting children up to 5 years of age have an effect in the reduction of VT carriage disease. However, in crises or settings with high prevalence of malnutrition, the high pneumococcal carriage prevalence is likely to extend to older age groups. Single dose vaccination of a larger age group might be needed to control VT circulation. Currently, for GAVI-supported countries such as Niger, PCV13 vaccine has a cost of US$3 per dose. Pneumosil®, a PCV10 manufactured by Serum institute of India Ltd has the lowest price of all WHO prequalified vaccines, at US$2 per dose.
Mass campaigns targeting large groups require many doses and might not be sustainable over time. Fractional doses of PCV could be a solution to overcome the high PCV costs, increase vaccine access and expand vaccination benefits through alternative strategies. The study population (ages 1-9) stems from an LSHTM modelling study.
Objectives of the study Primary objective: evaluate whether the full dose of PCV is superior to the absence of vaccine and then if a single 20% dose of PCV is non-inferior to a full dose in carriage reduction.
Secondary objectives:
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Vaccinators will not be blinded, but participants will not know vaccine dosage allocation. Laboratory staff (outcome assessors) will be blinded to their group allocation.
入排标准
- 年龄范围
- 1 Year 至 9 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Single full dose of PCV 10
27 clusters randomized to receive a vaccination campaign with the full dose.
干预措施: PCV10 full dose (Biological)
Single fractional dose of PCV10 (1/5)
27 clusters randomized to receive a vaccination campaign with the fractional dose (1/5).
干预措施: PCV10 fractional dose (Biological)
结局指标
主要结局
Effect of a Single Dose PCV10 Campaign in the Reduction of VT Carriage
时间窗: During three months of vaccination campaign, and 6 months post-vaccination campaign
The effect of a single dose PCV10 campaign in the reduction of VT carriage will be assessed by: first, assessing the superiority of a campaign using full doses of PCV10 compared to control group without vaccination; and second, by establishing the non-inferiority of a campaign using fractional doses of PCV10 compared to a campaign using full doses. NP carriage will be measured in the 3 study arms (full dose arm, fractional dose arm and control arm) in a baseline survey implemented prior to the vaccination campaign and in a post-vaccination survey. The NP carriage of VT S. pneumoniae will be measured as the proportion of participants that are colonized with any of the 10 serotypes covered by PCV10 at each time point. The reduction in NP carriage will be calculated by comparing the proportion of children carrying VT pneumococci 6 months post-vaccination to baseline, at the time of vaccination. The prevalence of colonization of non-VT serotypes will also be described at both timepoints.
次要结局
- Vaccine Safety Monitoring(Up to 28 days after vaccination)
- Cost-effectiveness and Modeling(Within 2 years of study start.)
- Facilitators and Barriers to Implementing Mass Campaigns of Fractional Dose PCV(Within 2 years of study start.)