A Pragmatic Phase III Multicentre Clinical Trial to Evaluate the Safety and Effectiveness of a Single Dose of an Albendazole-Ivermectin Coformulation vs Albendazole for Preventive Chemotherapy of Soil-Transmitted Helminth Infections in School-Aged Children
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20,000
- 试验地点
- 2
- 主要终点
- AEs and SAEs record of participants treated with FDC compared to ALB.
研究概览
简要总结
An open-label, randomized by school, two-arm pragmatic trial, will be conducted involving two study sites in Sub-Saharan-Africa (SSA), Ghana and Kenya, to evaluate safety and effectiveness of the newly developed fixed dose combination (FDC) of albendazole (ALB) and ivermectin (IVM) as a single dose to treat Soil-Transmitted Helminths (STH), compared to the standard dose ALB single dose for the treatment and control of STH (REALISE study: Real World Evaluation of an Albendazole-Ivermectin Coformulation Safety and Effectiveness). The general objectives are to validate the benefits of FDC through this pragmatic trial in a context of mass drug administration (MDA) programme to evaluate the safety as a primary endpoint and effectiveness profile as a secondary endpoint, in a large population of school-aged children.
详细描述
In the REALISE study a total of 20,000 children will be enrolled approximately in both countries for the safety cohort, 10,000 children in around 30 schools per country (5,000 per treatment arm). For the effectiveness cohort, REALISE study is planned to assess a total of approximately 4,500 participants in both countries, 2,250 children per country (75 children for each of the 30 schools and 1,125 children per treatment arm).
The REALISE study will have two study arms:
- Treatment arm 1: Single dose of a tablet of FDC 400 mg/18 mg IVM or 400 mg ALB/9 mg IVM, administered according to the following age criteria:
- For children from 5-14 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/9 mg IVM.
- For children from 15-17 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/18 mg IVM.
- Treatment arm 2: Single dose of a tablet of ALB 400 mg (active control arm).
Randomization will occur at the school level, and each eligible participant within a school will receive only one of the study treatments. Given the variable number of children in the Ghanaian and Kenyan schools, and that conducting the intervention for only a fraction of the school is not feasible, it may be possible to exceed the intended trial sample size. Efforts will be made to minimize this
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
- Single (Outcomes Assessor)
盲法说明
This is an open study. Participants and the study investigators assessing drug safety will not be blinded to treatment arms. Only the laboratory-based effectiveness measurement will be performed by blinded operators.
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Individuals of both sexes that attend the selected schools in the trial areas in Ghana and Kenya that meet the following criteria:
- •Age: 5 to 17 years old (included).
- •Height: over 110 cm.
- •Parental acceptance to participate in the study by obtaining written informed consent approved by the Ethics Committee. Written assent will also be obtained from children according to the local national legislation (12-17 years old).
排除标准
- •Epidemiological risk of being infected by Loa loa, defined as those who have visited any of the following countries: Angola, Cameroon, Central Africa Republic, Chad, Congo, Democratic Republic of the Congo, Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan.
- •Serious medical illness, defined as participants showing symptoms of acute illness which could hamper the participation in the trial, such as high-grade fever, severe diarrhoea, neurological symptoms or others, per investigator's criteria.
- •Any condition prevents the appropriate evaluation and follow-up of the participant, per the investigator's criteria.
- •Known hypersensitivity to any component of either study treatment.
- •Pregnant or first week post-partum: female participants who are post-menarche must have a negative urine pregnancy test at screening.
研究组 & 干预措施
Fixed Dose Combination (FDC) albendazole and Ivermectin (ALB/IVM )
Single dose of a tablet of FDC 400 mg/18 mg IVM or 400 mg ALB/9 mg IVM, administered according to the following age criteria:
- For children from 5-14 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/9 mg IVM
- For children from 15-17 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/18 mg IVM
干预措施: Pre-screening Phase (Drug)
Fixed Dose Combination (FDC) albendazole and Ivermectin (ALB/IVM )
Single dose of a tablet of FDC 400 mg/18 mg IVM or 400 mg ALB/9 mg IVM, administered according to the following age criteria:
- For children from 5-14 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/9 mg IVM
- For children from 15-17 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/18 mg IVM
干预措施: Screenig Phase (Drug)
Fixed Dose Combination (FDC) albendazole and Ivermectin (ALB/IVM )
Single dose of a tablet of FDC 400 mg/18 mg IVM or 400 mg ALB/9 mg IVM, administered according to the following age criteria:
- For children from 5-14 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/9 mg IVM
- For children from 15-17 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/18 mg IVM
干预措施: Randomization (Drug)
Fixed Dose Combination (FDC) albendazole and Ivermectin (ALB/IVM )
Single dose of a tablet of FDC 400 mg/18 mg IVM or 400 mg ALB/9 mg IVM, administered according to the following age criteria:
- For children from 5-14 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/9 mg IVM
- For children from 15-17 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/18 mg IVM
干预措施: Baseline Effectiveness Cohort (Drug)
Fixed Dose Combination (FDC) albendazole and Ivermectin (ALB/IVM )
Single dose of a tablet of FDC 400 mg/18 mg IVM or 400 mg ALB/9 mg IVM, administered according to the following age criteria:
- For children from 5-14 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/9 mg IVM
- For children from 15-17 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/18 mg IVM
干预措施: Day 0 Trial Intervention (Drug)
Fixed Dose Combination (FDC) albendazole and Ivermectin (ALB/IVM )
Single dose of a tablet of FDC 400 mg/18 mg IVM or 400 mg ALB/9 mg IVM, administered according to the following age criteria:
- For children from 5-14 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/9 mg IVM
- For children from 15-17 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/18 mg IVM
干预措施: Active Surveillance (study visit Day 1, Day 2 and Day 7) (Drug)
Fixed Dose Combination (FDC) albendazole and Ivermectin (ALB/IVM )
Single dose of a tablet of FDC 400 mg/18 mg IVM or 400 mg ALB/9 mg IVM, administered according to the following age criteria:
- For children from 5-14 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/9 mg IVM
- For children from 15-17 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/18 mg IVM
干预措施: Passive Surveillance (Drug)
Fixed Dose Combination (FDC) albendazole and Ivermectin (ALB/IVM )
Single dose of a tablet of FDC 400 mg/18 mg IVM or 400 mg ALB/9 mg IVM, administered according to the following age criteria:
- For children from 5-14 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/9 mg IVM
- For children from 15-17 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/18 mg IVM
干预措施: Post-Treatment Effectiveness Evaluation (Drug)
Albendazole (ALB)
Single dose of a tablet of ALB 400 mg (active control arm).
干预措施: Pre-screening Phase (Drug)
Albendazole (ALB)
Single dose of a tablet of ALB 400 mg (active control arm).
干预措施: Screenig Phase (Drug)
Albendazole (ALB)
Single dose of a tablet of ALB 400 mg (active control arm).
干预措施: Randomization (Drug)
Albendazole (ALB)
Single dose of a tablet of ALB 400 mg (active control arm).
干预措施: Baseline Effectiveness Cohort (Drug)
Albendazole (ALB)
Single dose of a tablet of ALB 400 mg (active control arm).
干预措施: Day 0 Trial Intervention (Drug)
Albendazole (ALB)
Single dose of a tablet of ALB 400 mg (active control arm).
干预措施: Active Surveillance (study visit Day 1, Day 2 and Day 7) (Drug)
Albendazole (ALB)
Single dose of a tablet of ALB 400 mg (active control arm).
干预措施: Passive Surveillance (Drug)
Albendazole (ALB)
Single dose of a tablet of ALB 400 mg (active control arm).
干预措施: Post-Treatment Effectiveness Evaluation (Drug)
结局指标
主要结局
AEs and SAEs record of participants treated with FDC compared to ALB.
时间窗: 7 days, active surveillance (Day 0 (1 hour), Day 1, Day 2 and Day 7 post-intervention) and passive surveillance (From Day 0 up to Day 6 post-intervention)
Adverse events will be recorded in the source documents and the electronic Case Report Form during the trial. The nature of the AE, its date and time of onset, duration and severity, therapy employed (only for SAEs) and the investigator's opinion of causality to the study drug with an alternate aetiology, if appropriate, will be documented. Changes in the severity of an AE will be documented to allow an assessment of the duration of the event at each level of intensity. Classification of the AEs and SAEs according to their frequency will be performed by the Sponsor at the end of the trial.
次要结局
- Reduction in T. trichiura prevalence in participants treated with FDC compared with ALB.(Baseline, 21 days and 11 months post-intervention)