Azithromycine Pour la Vie Des Enfants au Niger - Implémentation et Recherche: Essai mortalité et résistance (Azithromycin for Child Survival in Niger: Mortality Trial and Resistance Trial)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 864,493
- 试验地点
- 1
- 主要终点
- Prevalence of Resistance to Macrolides - Nasopharyngeal Swabs (1-59 Months Old)
研究概览
简要总结
The MORDOR trial found that biannual distribution of azithromycin to children 1-59 months old reduced child mortality. The World Health Organization (WHO) released conditional guidelines for this intervention, which include targeting azithromycin distributions to children 1-11 months of age in high mortality settings.Targeting treatment to children 1-11 months old could reduce antimicrobial resistance by limiting antibiotic distributions while treating children at the highest mortality risk. However, this targeted intervention has not yet been tested.
The AVENIR mortality/resistance trial aims to assess the efficacy of age-based targeting of biannual azithromycin distribution on mortality as well as determine the impact of age-based targeting on antimicrobial resistance.
详细描述
In the Mortality/Resistance trial, 3,000 communities in the Dosso and Tahoua regions of Niger will be randomized to one of three arms: 1) azithro 1-11: biannual oral azithromycin to children 1-11 months old with biannual oral placebo to children 12-59 months old, 2) azithro 1-59: biannual oral azithromycin to children 1-59 months old, or 3) placebo: biannual oral placebo to children 1-59 months old. Interventions will be delivered biannually through a door-to-door census. Mortality will also be monitored through biannual census data collection, which will be used to adaptively allocate treatment assignments after the first year. Communities will retain an allocation for 4 distributions before being re-randomized.
Antimicrobial resistance will be monitored using cluster sampling of treated and untreated children and adults in the Dosso region.
To compare costs, coverage, and acceptability of treating 1-11-month-old children only vs children 1-59 months old, an additional 80 communities in the Dosso region will be selected. These communities will be randomized in a 1:1 fashion to either receive 1) distribution of open-label azithromycin to children 1-11 months old with no intervention to children 12-59 months old or 2) distribution of open-label azithromycin to children 1-59 months old. The primary outcome for this substudy will be community-level costs per dose delivered. Secondary outcomes include program costs, treatment coverage, and acceptability of the intervention according to community leaders, community health workers, and caregivers of eligible children.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
In the mortality/resistance trial, we will use a matching placebo to mask study arm allocation. Placebo will be identical to azithromycin in appearance, smell, and packaging. Treatment assignment will be masked by assigning a series of upper- and lower-case letters to each trial, age group, and treatment arm. Those masked to study arm allocation include participants, investigators, most study personnel including study personnel administering treatment and collecting data on mortality outcomes, and laboratory personnel processing samples for resistance outcomes. Unmasked personnel include the trial biostatistician and data analyst responsible for implementing the randomization sequence and key members of Pfizer staff.
In a subset of 80 communities, open-label azithromycin will be distributed with no masking of participants, implementors, or outcome assessors.
入排标准
- 年龄范围
- 1 Month 至 59 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Intervention
- •At the community-level, eligibility includes:
- •Inclusion Criteria:
- •Location in Dosso, Tahoua, Maradi, Zinder, or Tillabéri regions
- •Population 250 to 2,499*
- •Distance > 5 km from district headquarters town
- •Distinguishable from neighboring communities
- •Verbal consent of community leader(s)
排除标准
- •Inaccessible or unsafe for study team
- •"Quartier" designation on national census *Population size as estimated from the most recent national census or projections
- •At the individual-level, eligibility includes:
- •Inclusion criteria:
- •Age 1-59 months
- •Primary residence in a study community
- •Verbal consent of caregiver/guardian for study participation
- •Weight ≥ 3.0 kg (*no weight limits in communities using age-based dosing)
- •Exclusion criteria:
- •Known allergy to macrolides
- •Population-based sample collections
- •At the community-level, eligibility includes:
- •Inclusion Criteria:
- •Location in Dosso
- •Distinguishable from neighboring communities
- •Verbal consent of community leader(s)
- •Exclusion criteria:
- •Inaccessible or unsafe for the study team
- •Included in MORDOR trials
- •Not randomly selected
- •Received treatment prior to sample collection
- •At the individual-level, eligibility includes:
- •Inclusion Criteria:
- •Age 1-59 months or 7-12 years or caregiver/guardian of a child eligible for treatment
- •Primary residence in a study community selected for sample collections
- •Verbal consent of caregiver/guardian for study participation
- •Exclusion criteria:
- •An individual is not on the list of randomly selected participants from the census
研究组 & 干预措施
Azithro 1-59
Biannual age, weight- or height-based dose of oral azithromycin suspension to children 1-59 months old
干预措施: Azithromycin (Drug)
Placebo
Biannual weight- or height-based dose of oral placebo to children 1-59 months old
干预措施: Placebo (Other)
Azithro 1-11
Biannual weight- or height-based dose of oral azithromycin suspension to children 1-11 months old and oral placebo or no intervention to children 12-59 months old
干预措施: Placebo (Other)
Azithro 1-11
Biannual weight- or height-based dose of oral azithromycin suspension to children 1-11 months old and oral placebo or no intervention to children 12-59 months old
干预措施: Azithromycin (Drug)
结局指标
主要结局
Prevalence of Resistance to Macrolides - Nasopharyngeal Swabs (1-59 Months Old)
时间窗: After 4 distributions (approximately 24 months)
Prevalence of macrolide resistance among pneumococcus-positive nasopharyngeal swabs collected from children aged 1-59 months after 4 distributions. Resistance was assessed among culture-positive pneumococcal isolates from nasopharyngeal swabs.
Load of Genetic Determinants of Resistance to Macrolides - Rectal Swabs (1-59 Months Old)
时间窗: After 4 distributions (approximately 24 months)
Community-level load of macrolide antimicrobial resistance determinants in pooled rectal swabs collected from children aged 1-59 months after four biannual distributions. Rectal swabs from each community were pooled and analyzed using metagenomic DNA sequencing. Nonhost sequencing reads were aligned to an antimicrobial resistance reference database, and reads matching macrolide resistance determinants were summed and normalized to the total number of nonhost reads in the pooled sample. Values are reported as matched resistance reads per million nonhost reads (rM). Higher values indicate a greater abundance of macrolide resistance determinants. The values presented in the table are untransformed normalized counts.
All-cause Mortality (1-59 Months Old)
时间窗: from 6 months up to 2.5 years
Mortality rate (deaths per 1,000 person-years at risk) among children 1-59 months of age, comparing the azithro 1-59 and placebo arms.
All-cause Mortality (1-11 Months Old)
时间窗: from 6 months up to 2.5 years
Mortality rate (deaths per 1,000 person-years at risk) among children 1-11 months of age, comparing the azithro 1-11 and placebo arms.
All-cause Mortality (12-59 Months Old)
时间窗: from 6 months up to 2.5 years
Mortality rate (deaths per 1,000 person-years at risk) among children 12-59 months of age with rates compared between azithro 1-11 and azithro 1-59 communities.
次要结局
- Program Costs Per Dose Delivered(1 year)
- Mortality Rate by Weight-for-age Z-score Subgroup Among Infants Aged 1-11 Months(After 4 distributions (approximatively 24 month after first distribution))
- Load of Genetic Determinants of Resistance to Macrolides in Nasopharyngeal Swabs From Guardians(After 4 distributions (approximatively 24 month after first distribution))
- Load of Genetic Determinants of Resistance to Macrolides in Nasopharyngeal Swabs From Children Aged 7-12 Years(After 4 distributions, approximately 24 months)