Efficacy, Safety and Acceptability of Ascending Doses of Ivermectin in Combination With Albendazole for Trichuris Trichiura Infections in Preschool-aged Children: a Single-blind Randomised Controlled Dose-ranging Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- Cure Rate (CR) Against T. Trichiura
研究概览
简要总结
This study is a single-blind randomized controlled dose-ranging trial aiming at providing evidence on the on the optimal dose of co-administered ivermectin and albendazole in terms of efficacy, safety and acceptability in preschool-aged children (PSAC; aged 2-5 years) infected with whipworm (Trichuris trichiura) on Pemba Island, Tanzania. Additionally, the pharmacokinetics of the newly developed oro-dispersible tablets (ODTs) and the standard ivermectin tablets (Stromectol®) will be compared in this age group.
As measure of efficacy of the treatment the cure rate (percentage of egg-positive participants at baseline who become egg-negative after treatment) will be determined 14-21 days post-treatment.
详细描述
This study is a single-blind randomized controlled dose-ranging trial aiming at providing evidence on the optimal dose of co-administered ivermectin and albendazole in terms of efficacy, safety and acceptability in preschool-aged children (PSAC; aged 2-5 years) infected with whipworm (Trichuris trichiura) on Pemba Island, Tanzania. Additionally, the pharmacokinetics of the newly developed ODTs and the standard ivermectin tablets (Stromectol®) will be compared in this age group.
The primary objective of the trial is to comparatively assess the efficacy in terms of cure rate (CR) against T. trichiura infections among PSAC receiving different doses of ivermectin.
The secondary objectives of the trial are to compare the egg reduction rates (ERRs) of the treatment regimens against T. trichiura, to determine the CRs and ERRs of the drugs in study participants co-infected with A. lumbricoides and hookworm, and to evaluate the safety and tolerability of the treatment regimens.
In addition, this study aims to characterize population pharmacokinetics of the ivermectin ODTs compared to standard tablets in T. trichiura infected individuals, and to assess the acceptability of the treatments.
After obtaining informed consent from parents and/or caregivers, the medical history of the participants will be assessed with a standardized questionnaire, in addition to a clinical examination carried out by the study physician before treatment. Enrollment will be based on two stool samples, which 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.
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 (Participant)
盲法说明
Single (Participant) Treatment allocation will be masked using appearance-matched placebos.
入排标准
- 年龄范围
- 2 Years 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •individuals aged 2-5 years (24-71 months; confirmed by birth certificate or similar document)
- •having given written informed consent signed by parents/caregivers
- •being able and willing to provide two stool samples at baseline and at follow-up assessment (14-21 days)
- •having at least two out of four Kato-Katz slides positive for T. trichiura at baseline
- •being able and willing to be examined by a study physician before and after treatment
排除标准
- •presence or signs of major systemic illness, e.g. fever (temporal body temperature of >38.0°C), severe anaemia (haemoglobin level of <70 g/l)
- •history of severe acute disease or unmanaged, severe chronic disease (i.e., condition is not as therapeutically controlled as necessary)
- •use of anthelminthic drugs during study period
- •known allergy to study medication (i.e., ivermectin or albendazole)
- •being prescribed or taking concomitantly medication with known contraindications or drug interactions with the study medication
- •concurrent participation in other clinical trials
研究组 & 干预措施
Arm A: Ivermectin ODT Placebo & Albendazole
Placebo for ivermectin (oro-dispersible tablets) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Albendazole 400 mg Oral Tablet (Drug)
Arm A: Ivermectin ODT Placebo & Albendazole
Placebo for ivermectin (oro-dispersible tablets) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Placebo Ivermectin ODT (Drug)
Arm B: Ivermectin ODT 100 µg/kg & Albendazole
Combination therapy of ivermectin (100 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Ivermectin 1.5 mg ODT (Drug)
Arm B: Ivermectin ODT 100 µg/kg & Albendazole
Combination therapy of ivermectin (100 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Albendazole 400 mg Oral Tablet (Drug)
Arm C: Ivermectin ODT 200 µg/kg & Albendazole
Combination therapy of ivermectin (200 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Ivermectin 1.5 mg ODT (Drug)
Arm C: Ivermectin ODT 200 µg/kg & Albendazole
Combination therapy of ivermectin (200 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Albendazole 400 mg Oral Tablet (Drug)
Arm D: Ivermectin ODT 300 µg/kg & Albendazole
Combination therapy of ivermectin (300 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Ivermectin 1.5 mg ODT (Drug)
Arm D: Ivermectin ODT 300 µg/kg & Albendazole
Combination therapy of ivermectin (300 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Albendazole 400 mg Oral Tablet (Drug)
Arm E: Ivermectin ODT 400 µg/kg & Albendazole
Combination therapy of ivermectin (400 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Ivermectin 1.5 mg ODT (Drug)
Arm E: Ivermectin ODT 400 µg/kg & Albendazole
Combination therapy of ivermectin (400 µg/kg using oro-dispersible tablets of 1.5 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Albendazole 400 mg Oral Tablet (Drug)
Arm F: Ivermectin standard tablets & Albendazole
Combination therapy of ivermectin (Stromectol®, 200 µg/kg using tablets of 3 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Ivermectin 3 mg Oral Tablet (Drug)
Arm F: Ivermectin standard tablets & Albendazole
Combination therapy of ivermectin (Stromectol®, 200 µg/kg using tablets of 3 mg) and albendazole (Zentel®, 1 tablet of 400 mg) administered orally at day 0
干预措施: Albendazole 400 mg Oral Tablet (Drug)
结局指标
主要结局
Cure Rate (CR) Against T. Trichiura
时间窗: 14-21 days post-treatment
The CR will be calculated as the proportion of participants converting from being egg-positive pre-treatment to egg-negative post-treatment.
次要结局
- Egg Reduction Rate (ERR) Against T. Trichiura (Geometric Mean ERR)(14-21 days post-treatment)
- Egg Reduction Rate (ERR) Against T. Trichiura (Arithmetic Mean ERR)(14-21 days post-treatment)
- Cure Rate (CR) Against A. Lumbricoides(14-21 days post-treatment)
- Egg Reduction Rate (ERR) Against A. Lumbricoides (Geometric Mean ERR)(14-21 days post-treatment)
- Egg Reduction Rate (ERR) Against A. Lumbricoides (Arithmetic Mean ERR)(14-21 days post-treatment)
- Cure Rate (CR) Against Hookworm(14-21 days post-treatment)
- Egg Reduction Rate (ERR) Against Hookworm (Geometric Mean ERR)(14-21 days post-treatment)
- Egg Reduction Rate (ERR) Against Hookworm (Arithmetic Mean ERR)(14-21 days post-treatment)
- Number of Participants Reporting Adverse Events (AEs)(3 hours, 24 hours and 14-21 days post-treatment)
研究者
Jennifer Keiser
Prof. Dr.
Swiss Tropical & Public Health Institute