Efficacy and Safety of Moxidectin and Albendazole Compared to Ivermectin and Albendazole Co-administration in Adolescents Infected With Trichuris Trichiura: a Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 536
- 试验地点
- 1
- 主要终点
- Egg Reduction Rate Against T. Trichiura
研究概览
简要总结
The aim of this randomized controlled trial is to provide evidence on the efficacy and safety of co-administered moxidectin and albendazole compared to co-administered ivermectin and albendazole, and to assess the efficacy of the drug combinations compared to monotherapies in adolescents aged 12-19 years against infection with T. trichiura.
The efficacy of the different treatments will be determined 14-21 days, 5-6 weeks and 3 months post-treatment. Two fecal samples will be collected at each time-point assessment. The geometric mean based egg reduction rate (ERR) of T. trichiura egg counts will be assessed by Kato-Katz microscopy pre-treatment and 14-21 days post-treatment.
This trial will be conducted as a school-based study on Pemba Island (Zanzibar, Tanzania).
详细描述
We designed a non-inferiority trial to show that co-administered moxidectin and albendazole is non-inferior compared to co-administered ivermectin and albendazole in adolescents aged 12-19 years on Pemba Island (Tanzania). From previous studies conducted by our group, we expect similar efficacies from the combination moxidectin/ albendazole compared to ivermectin/ albendazole. However, moxidectin might be advantageous in terms of the drug's longer half-life and in areas with possible emerging ivermectin resistance. This study will allow comparing the efficacy of the two available co-administrations and will provide further insights on the potential value of moxidectin/ albendazole. Our data will pave the way for possible large scale, multi country follow-up studies. As recommended for new combination therapies, we simultaneously assess superiority of the drug combinations compared to monotherapies.
The primary objective is to demonstrate that co-administered moxidectin (8 mg) / albendazole (400 mg) is non-inferior to ivermectin (200 µg/kg) / albendazole (400 mg) in terms of egg reduction rates (ERRs) against T. trichiura infections assessed by Kato-Katz at 14-21 days post-treatment in adolescents aged 12-19 years using a non-inferiority margin of 2 percentage-points.
The secondary objectives of the trial are:
- Efficacy assessments of combination therapies require demonstration of superiority against the respective monotherapies. Therefore, the trial has five different treatment groups: moxidectin (8 mg) / albendazole (400 mg) combination, ivermectin (200 µg/kg) / albendazole (400 mg) combination, albendazole (400 mg) monotherapy, ivermectin (200 µg/kg) monotherapy and moxidectin (8 mg) monotherapy.
- to determine the CRs of the drug regimens against T. trichiura
- to evaluate the safety and tolerability of the treatment
- to determine the CRs and ERRs of the treatment schemes in study participants infected with hookworm and A. lumbricoides
- to investigate potential extended effects on follow-up helminth prevalences (5-6 weeks and 3 months post-treatment) of the treatment regimens
- to assess diagnostic performance and compare CRs based on egg counts retrieved from novel diagnostic tools (FECPAK-G2 and/or PCR) compared to standard microscopy
- to characterize population PK parameters, as well as drug-drug interactions of active study treatments following single and co-administration in T. trichiura infected adolescents. If a dose-response is observed, a PK/PD analysis will further be performed
The study will be carried out in adolescents aged 12-19 years attending secondary schools on Pemba Island, Tanzania. After consenting, all participants will be asked to provide two stool samples (within a maximum of 7 days) at each time-point assesment. From each stool specimen, duplicate Kato-Katz thick smears (41.7 mg each) will be prepared and read under a microscope for eggs of T. trichiura, A. lumbricoides and hookworm by experienced 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 (Outcomes Assessor)
盲法说明
Open Label with masked outcomes assessors
入排标准
- 年龄范围
- 12 Years 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged between 12 and 19 years.
- •Written informed consent signed by either parents/caregivers for underage adolescents (aged 12-17 years) or by the participant him/herself (18-19 years of age); and written assent by underage participant.
- •Agree to comply with study procedures, including provision of two stool samples at the beginning (baseline) and on three follow-up assessments (14-21 days, 5-6 weeks and 3 months after treatment).
- •Willing to be examined by a study physician prior to treatment.
- •At least two slides of the quadruple Kato-Katz thick smears positive for T. trichiura and infection intensities of at least 48 EPG.
排除标准
- •No written informed consent by individual or caregiver and/or no written assent by minors
- •Presence or signs of major systemic illnesses, e.g. body temperature ≥ 38°C, severe anemia (below 80g/l Hb according to WHO) upon initial clinical assessment.
- •History of acute or severe chronic disease.
- •Recent use of anthelmintic drug (within past 4 weeks).
- •Attending other clinical trials during the study.
- •Pregnancy, lactating, and/or planning to become pregnant within the next 6 months.
- •Known allergy to study medications (i.e. albendazole, ivermectin or moxidectin).
- •Taking medication with known interaction on study drugs.
研究组 & 干预措施
A: moxidectin (8 mg) / albendazole (400 mg)
Combination therapy of moxidectin (8 mg using 2 mg tablets) plus albendazole (Zentel®, 400 mg, single tablet) administered orally at day 0
干预措施: moxidectin (8 mg) / albendazole (400 mg) (Drug)
B: ivermectin (200 µg/kg) / albendazole (400 mg)
Combination therapy of ivermectin (Stromectol®, 200 µg/kg using 3 mg tablets) plus albendazole (Zentel®, 400 mg, single tablet) administered orally at day 0
干预措施: ivermectin (200 µg/kg) / albendazole (400 mg) (Drug)
C: albendazole (400 mg)
Monotherapy of albendazole (400 mg) administered orally at day 0 Other names: Zentel®
干预措施: ALBENDAZOLE 400 Mg ORAL TABLET [ZENTEL] (Drug)
D: ivermectin (200 µg/kg)
Monotherapy of ivermectin ( 200 µg/kg using 3 mg tablets) administered orally at day 0 Other names: Stromectol®
干预措施: ivermectin (200 µg/kg) (Drug)
E: moxidectin (8 mg)
Monotherapy of moxidectin (8 mg using 2 mg tablets) administered orally at day 0
干预措施: moxidectin (8 mg) (Drug)
结局指标
主要结局
Egg Reduction Rate Against T. Trichiura
时间窗: 14-21 day post-treatment
Egg reduction rate is calculated as the relative reduction in the group geometric mean egg output after co-administration of moxidectin/ albendazole and ivermectin/ albendazole assessed at 14-21 days post-treatment compared to the baseline levels.
次要结局
- Number of Participants With Adverse Events(3 hours, 24 hours, 14-21 days, 5-6 weeks and 3 months post-treatment)
- Superiority in Terms of Cure Rates (CRs)(14-21 day post-treatment)
- Cure Rates Against T. Trichiura(14-21 day post-treatment)
- Extended Effects (Egg Reduction Rate) on Follow-up of T. Trichiura: 5-6 Weeks(5-6 weeks post-treatment)
- Extended Effects (Cure Rate) on Follow-up of T. Trichiura: 5-6 Weeks(5-6 weeks post-treatment)
- Extended Effects (Egg Reduction Rate) on Follow-up of T. Trichiura: 3 Months(3 months post-treatment)
- Extended Effects (Cure Rates) on Follow-up of T. Trichiura: 3 Months(3 months post-treatment)
- Egg Reduction Rates Against Concomitant Soil-transmitted Helminth Infections: Hookworm(14-21 days post-treatment)
- Cure Rates Against Concomitant Soil-transmitted Helminth Infections: Hookworm(14-21 days post-treatment)
- Extended Effects (Egg Reduction Rate) on Follow-up of Hookworm: 5-6 Weeks(5-6 weeks post-treatment)
- Extended Effects (Cure Rate) on Follow-up of Hookworm: 5-6 Weeks(5-6 weeks post-treatment)
- Extended Effects (Egg Reduction Rate) on Follow-up of Hookworm: 3 Months(3 months post-treatment)
- Extended Effects (Cure Rate) on Follow-up of Hookworm: 3 Months(3 months post-treatment)
- Egg Reduction Rates Against Concomitant Soil-transmitted Helminth Infections: Ascaris Lumbricoides(14-21 days post-treatment)
- Cure Rates Against Concomitant Soil-transmitted Helminth Infections: Ascaris Lumbricoides(14-21 days post-treatment)
- Extended Effects (Egg Reduction Rate) on Follow-up of A. Lumbricoides: 5-6 Weeks(5-6 weeks post-treatment)
- Extended Effects (Cure Rate) on Follow-up of A. Lumbricoides: 5-6 Weeks(5-6 weeks post-treatment)
- Extended Effects (Egg Reduction Rate) on Follow-up of A. Lumbricoides: 3 Months(3 months post-treatment)
- Extended Effects (Cure Rate) on Follow-up of A. Lumbricoides: 3 Months(3 months post-treatment)
研究者
Jennifer Keiser
Prof. Dr.
Swiss Tropical & Public Health Institute