Assessing Safety and Efficacy of Ivermectin and Albendazole Combination Therapy for Soil-transmitted Helminthiasis in Pre-school-aged Children (PSAC) in Bangladesh
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
Background (brief):
- Burden:
Soil-transmitted helminth (STH) infections are a major public health problem, primarily affecting children. Although STH prevalence has decreased to 14% in Bangladesh, over 47 million preschool- and school-age children still live in high-risk areas. 2. Knowledge gap:
Albendazole shows 94-100% efficacy against A. lumbricoides but only 39-60% against T. trichuria. Ivermectin is also effective against hookworm and T. trichuria. Combining ivermectin with albendazole may be more effective than using either drug alone, but this combined therapy for STH has not yet been studied in Bangladesh. 3. Relevance:
STHs significantly impact children's nutrition, hindering health, growth, cognition, and learning. The national deworming program achieved 98.3% treatment coverage, but only 76.2% of PSAC were dewormed using self-prescribed medicines.
Hypothesis (if any):
The combination therapy of Albendazole and Ivermectin is more effective than Albendazole alone for treating soil-transmitted helminths in preschool-age children in Bangladesh
Objectives:
- To compare the safety and efficacy of Albendazole and Ivermectin combination therapy with Albendazole monotherapy in preschool-aged children
- To evaluate post-treatment egg reduction rates for various helminths at different time points
- To determine the median time to re-infection following different anti-helminth interventions for various STH
Methods:
This Phase IIa single-blinded, randomized controlled trial will evaluate the safety and efficacy of ivermectin and albendazole combination therapy versus standard albendazole monotherapy for STH in 2-5 years in rural Belkuchi, Sirajganj. A total of 110 PSAC with confirmed STH will be randomly assigned to two treatment arms. Field activities and laboratory analysis will use the Kato-Katz technique for microscopic examination.
Outcome measures/variables:
- Evaluate the safety and efficacy of ivermectin and albendazole combination therapy for STH
- Evaluate the statistically significant impact on patient clinical outcomes, cure rate, and egg reduction rate
- Correlate changes in Cure Rate and Egg Reduction Rate for different STH at various time points
详细描述
Description of the Research Project
Background of the Project including Preliminary Observations:
Epidemiology of Soil-transmitted helminthiasis Soil-transmitted helminthiasis (STH) infections are a group of parasitic infections caused by Ascaris lumbricoides (AL), Trichuris trichiura (TT), Ancylostoma duodenale (AD) and Necator americanus (NA) (hookworms). This infection is transmitted to humans by contaminated soil by human faeces containing parasite eggs. These infections impact the most impoverished and marginalized communities that lack access to clean water, sanitation, and proper hygiene, particularly in tropical and subtropical regions. At the same time, the highest prevalence is documented in sub-Saharan Africa, China, South America, and Asia. STH is a significant public health threat, with an estimated 1.5 billion people or 24% of the world population resulting in a loss of two million disability-adjusted life years.
The nutritional status of STH-infected children is often affected, eventually leading to impaired health, growth, cognition, and educational outcomes. High helminth intensity and polyparasitism may cause malnourishment and morbidity, which may result in death. Because of physical barrier and/or competition for food, helminths may make human hosts' malnutrition worse. Insufficient absorption of micronutrients and intestinal blood loss are more intricately linked to anaemia through an unknown process. The overall effect may change the children's cognitive development, including memory, reaction time, learning, and intrinsic intelligence. Children in preschool are not currently included in regular deworming programs for STH. However, the research indicates that children get infected soon after weaning and continue to be infected throughout childhood and adolescence. Children are negatively impacted by infections long before attending school, which exacerbates the long-term health risks of STH infection. Epidemiological research conducted among SACs demonstrated that STHs had a direct impact on student performance and absenteeism. So, deworming may play vital roles for preschool-aged children before entering school.
Several demographic groups are considered eligible for routine deworming, including preschool-aged children (PSAC) and school-aged children (SAC). In Bangladesh, STH was prevalent among 79.8% of school-age children (SAC) in 2005, which dropped to 14% in recent times. The prevalence is higher in slums or low socio-economic clusters (around 50.54%) due to poor hygiene and malnutrition, despite homogenous mass drug administration, MDA. More than one-third (36.3%) of SAC are re-infected with at least one helminth within six months of the MDA, with the highest prevalence of TT (27.5%) and 12.4 % of multiple helminth infections, which indicates the inefficiency of current PC.
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 study will be a single-blinded clinical trial. The investigators and study physicians will not be blinded. The investigators are not using any placebo arm for this trial; the approach to concealing the treatment arm by random selection of the study participants will avoid selection bias in the study. However, the primary objective of the study is a cure assessment of STH infection, which will be performed based on the egg reduction rate (ERR) with stool samples. To ensure the avoidance of any bias in the test, the laboratory personnel doing the procedures will be blinded.
入排标准
- 年龄范围
- 2 Years 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged within 2-5 years
- •Height > 90 cm and Weight > 15 kg
- •Both Stunted (The WHO-recommended height-for-age Z (HAZ) cut-off point is <-2 SD) and Healthy children (The WHO-recommended height-for-age Z (HAZ) cut-off point is >-1 SD)
- •Confirmed case of STH having single/co-infection of TT/hookworm/AL
- •Clinically healthy
- •Not received any medications for STH within the last six months
- •Guardians willing to let the children participate voluntarily through informed written consent
排除标准
- •Non-compliance with any inclusion criteria
- •Known severe allergies or adverse reactions to any of the study drugs
- •Having any pre-existing chronic disease
- •Recent participation in any clinical trials (within 1 year)
- •Inability to comply with the study requirements, including follow-up visits and treatment adherence
- •Guardians unwilling to let the children participate
研究组 & 干预措施
Treatment Arm - 1
A single dose of Albendazole 400mg + Ivermectin (200 µg/kg) combination therapy
干预措施: A single dose of Albendazole 400mg + Ivermectin (200 µg/ kg) combination therapy (Drug)
Treatment Arm - 2
A single dose of 400 mg Oral Albendazole monotherapy
干预措施: A single dose of 400 mg Oral Albendazole monotherapy (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: Through study completion, an average of 1 year
The investigators will determine the safety of ivermectin and albendazole combination therapy for STH among preschool-age children (ages 2-5 years old) by assessing severe adverse events (SAEs) assessed by CTCAE v4.0. An adverse event will be defined as severe if it causes or contributes to the death or hospitalization for life-threatening conditions or results in persistent or significant disability or incapacity or a medically significant event. Any SAE occurrence for any child will be considered unsafe for that child.
Determine statistically significant effect of combination therapy
时间窗: 3 weeks, 3 months, 6 months, 9 months, 12 months after baseline enrolment
The investigators will determine whether the efficacy of ivermectin and albendazole combination therapy has a statistically significant effect (p \< 0.05) on cure rates (CR) and egg reduction rates (ERR) compared to albendazole monotherapy.
次要结局
- Determine statistically significant effect of combination therapy on patient's nutritional status based on z-scores(3 months, 6 months, 9 months, 12 months after baseline enrolment)
- Correlate and compare changes in CR and ERR at different time points(3 weeks, 3 months, 6 months, 9 months, 12 months after baseline enrolment)
- Determine statistically significant effect of combination therapy on patient's clinical condition (anaemia) based on haemoglobin count(At Baseline and 3 months after baseline enrolment)