Efficacy and Safety of Ascending Dosages of Albendazole Against T. Trichiura and Hookworm in Preschool- and School-aged Children and Adults: a Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 700
- 试验地点
- 1
- 主要终点
- Cure Rate Against T. Trichiura and Hookworm Infections
研究概览
简要总结
This study is a single-blind randomized clinical trial conducted in rural Côte d'Ivoire. This study aims at providing evidence on the dose-response of increasing oral albendazole dosages against whipworm (T. trichiura) and hookworm infections in preschoolers (2-5 years), school-aged children (6-12 years) and adults (≥ 21 years).
The primary objective is to determine cure rates (primary end point, i.e. conversion from being egg positive pre-treatment to egg negative post-treatment). Secondary objectives involve the determination of egg reduction rates (the reduction in the number of excreted eggs from baseline (prior to treatment) to follow-up) and the assessment of safety of ascending dosages of albendazole (secondary end points). In addition, key pharmacokinetic parameters will be determined from blood samples collected with a micro-sampling device (secondary end point).
详细描述
This study is a single-blind randomized clinical trial conducted in Côte d'Ivoire. This study aims at providing evidence on the efficacy and safety of ascending oral albendazole dosages in children and adults infected with T. trichiura and hookworm. In preschool-aged children (2-5 years) (i) 200 mg, (ii) 400 mg and (iii) 600 mg; in schoolchildren (6-12 years) and adults (≥ 21 years) (i) 200 mg (only for hookworm infections), (ii) 400 mg, (iii) 600 mg and (iv) 800 mg will be administered and efficacy, safety and pharmacokinetic parameters will be assessed.
The primary objective is to determine the dose-response based on cure rates of albendazole in preschool-aged children (2-5 years), school-aged children (6-12 years) and adults (≥ 21 years) infected with T. trichiura and hookworm.
The secondary objectives of the trial are to determine the efficacy based on egg reduction rates of albendazole in preschool-aged children, school-aged children and adults, to determine an exposure (including length of time that the drug concentration is above the MIC, Cmax, AUC)-response correlation of albendazole in preschool-aged children, school-aged children and adults, to evaluate the safety and tolerability of albendazole in preschool-aged children, school-aged children and adults, and to determine the efficacy against concomitant soil-transmitted helminthiasis (Ascaris lumbricoides).
After obtaining informed consent from individual/parents and/or caregiver, the medical history of the participants will be assessed with a standardized questionnaire, in addition to a clinical examination and venipuncture to examine biochemical parameters in the blood carried out by the study physician before treatment. Enrollment will be based on two stool samples that will be collected, if possible, on two consecutive days or otherwise within a maximum of 5 days.
All stool samples will be examined with duplicated Kato-Katz thick smears by experienced laboratory technicians. Randomization of participants into the treatment arms will be stratified according to intensity of infection. All participants will be interviewed before treatment, 3 and 24 hours and 3 weeks after treatment about the occurrence of adverse events. Children and adults will be sampled using finger pricking for micro-blood sampling at 0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing.
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
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female adults (≥21 years), preschool-aged children (2-5 years) and school-aged children (6-12 years) infected with T. trichiura/hookworm
- •Written informed consent/assent signed from parent/guardian
- •Positive for T. trichiura/hookworm by at least two slides of the quadruple Kato-Katz thick smears and infection intensities of at least 100 eggs per gram of stool (EPG)
- •Agree to comply with study procedures, including provision of two stool samples at the beginning (baseline) and approximately three weeks after treatment (follow-up).
排除标准
- •Presence of acute or uncontrolled systemic illnesses (e.g. severe anemia, infection, clinical malaria) as assessed by a medical doctor, upon initial clinical assessment and liver function tests.
- •Known or reported history of chronic illness such as HIV, acute or chronic hepatitis, cancer, diabetes, chronic heart disease or renal disease.
- •Prior treatment with anthelmintics (eg, diethylcarbamazine [DEC], suramin, ivermectin, mebendazole or albendazole) within 4 weeks before planned test article administration.
- •Received any investigational drugs or investigational devices within 4 weeks before administration of test article that may confound safety and/or efficacy assessments.
- •Known or suspected allergy to benzimidazoles.
- •Pregnant (urine testing) or breastfeeding women
研究组 & 干预措施
200 mg albendazole
against T. trichiura in preschool-aged children or against hookworm infections in preschool-aged children, school-aged children and adults
干预措施: Albendazole (Drug)
400 mg albendazole
against T. trichiura in preschool-aged children, school-aged children and adults or against hookworm infections in preschool-aged children, school-aged children and adults
干预措施: Albendazole (Drug)
600 mg albendazole
against T. trichiura in preschool-aged children, school-aged children and adults or hookworm infections in preschool-aged children, school-aged children and adults
干预措施: Albendazole (Drug)
800 mg albendazole
against T. trichiura in school-aged children and adults or against hookworm infections in school-aged children and adults
干预措施: Albendazole (Drug)
Placebo
against T. trichiura in preschool-aged children, school-aged children and adults or hookworm infections in preschool-aged children, school-aged children and adults
干预措施: Placebo (Drug)
结局指标
主要结局
Cure Rate Against T. Trichiura and Hookworm Infections
时间窗: 14-21 days after treatment
The conversion from being egg positive pre-treatment to egg negative post-treatment, or cure rate (CR).
次要结局
- Egg-reduction Rate (ERR) Against T. Trichiura and Hookworm Infections, Respectively(14-21 days after treatment)
- Time to Reach Cmax (Tmax) of Albendazole Sulphoxide(0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing)
- Maximum Concentration (Cmax) of Albendazole Sulphoxide(0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing)
- Area Under the Curve (AUC) of Albendazole Sulphoxide(0, 1, 2, 3, 4, 6, 8, 24 hours post-dosing)
研究者
Jennifer Keiser
Prof. Jennifer Keiser, PhD
Swiss Tropical & Public Health Institute