Combination Therapies for Trichuris Trichiura Infection in Schoolchildren in Honduras

Randomized, Open-Label, Assessor-Blinded Clinical Trial of Combination Therapies Versus Standard Treatment for Trichuris Trichiura Infection in Schoolchildren in La Moskitia, Honduras

The goal of this Phase III clinical trial is to evaluate the efficacy, safety, and acceptability of different treatment regimens for Trichuris trichiura infection in schoolchildren aged 6 to 15 years living in La Moskitia, Honduras, an area with a high burden of soil-transmitted helminth infections.

The main questions it aims to answer are:

• Are combination treatments of albendazole and ivermectin more effective than albendazole alone for treating Trichuris trichiura infection?
• Does a fixed-dose combination (FDC) of albendazole and ivermectin achieve cure rates comparable to co-administration of the two drugs?
• How effective are the different treatment regimens against other soil-transmitted helminths, including Strongyloides stercoralis?
• What adverse events occur following treatment with the different regimens?
• How acceptable are the different treatment regimens to children and their caregivers?

Researchers will compare four treatment groups: placebo, albendazole alone, albendazole plus ivermectin, and a fixed-dose combination of albendazole plus ivermectin.

Participants will:

• Be randomly assigned to one of the four treatment groups.
• Receive a single dose of the assigned treatment.
• Provide stool samples before treatment and approximately 21 days after treatment.
• Undergo laboratory testing using quantitative real-time PCR (qPCR) to detect and quantify helminth infections.
• Be monitored for adverse events after treatment.
• Complete acceptability assessments together with their caregivers.

The study will provide evidence on the efficacy, safety, and acceptability of a fixed-dose combination of albendazole and ivermectin and its potential use as a simplified treatment strategy for the control of soil-transmitted helminth infections in endemic settings.

Soil-transmitted helminth (STH) infections remain among the most common neglected tropical diseases worldwide, affecting an estimated 1.5 billion people, particularly in tropical and subtropical regions with limited access to sanitation and healthcare. These infections are associated with anemia, malnutrition, impaired physical and cognitive development in children, and adverse pregnancy outcomes. Despite decades of preventive chemotherapy programs, STH infections continue to represent an important public health challenge in many endemic settings.

Current control strategies rely primarily on mass drug administration (MDA) using albendazole or mebendazole. While these medicines are effective against some STH species, their efficacy against Trichuris trichiura is limited, resulting in persistent transmission despite repeated treatment rounds. In addition, these regimens do not provide adequate treatment for Strongyloides stercoralis, a soil-transmitted helminth capable of causing chronic infection and severe complications in immunocompromised individuals.

Recognizing these limitations, the World Health Organization (WHO) Roadmap for Neglected Tropical Diseases 2021-2030 highlights the need for more effective interventions and strategies that can sustain progress toward the elimination of STHs as a public health problem. Combining existing anthelmintic drugs represents a practical and scalable approach to improving treatment efficacy while reducing the risk of emerging drug resistance.

Ivermectin has emerged as a key candidate for inclusion in integrated STH control strategies. The drug has an extensive record of safe use through large-scale public health programs targeting lymphatic filariasis and onchocerciasis and has been included in the WHO Model List of Essential Medicines. Clinical studies have shown that the combination of albendazole and ivermectin achieves substantially higher cure rates for T. trichiura than albendazole alone and also provides activity against S. stercoralis.

However, the operational use of ivermectin in preventive chemotherapy programs is complicated by the need for weight- or height-based dosing. This requirement increases logistical complexity, extends treatment time, and may result in dosing errors or exclusion of eligible individuals. To address these challenges, a fixed-dose combination (FDC) tablet containing albendazole and ivermectin has been developed. The FDC simplifies administration by providing a standardized dose in a single formulation while maintaining pharmacokinetic exposure comparable to co-administered drugs. Previous Phase II and Phase III studies have demonstrated promising efficacy and safety results, and the product has received a positive scientific opinion from the European Medicines Agency (EMA) for the treatment of multiple helminth infections.

Honduras represents an important setting for evaluating innovative treatment strategies against STHs. More than two million school-aged children require preventive chemotherapy, and T. trichiura remains highly prevalent despite repeated albendazole-based deworming campaigns. Previous studies conducted in Honduras have demonstrated improved efficacy of albendazole plus ivermectin compared with albendazole alone, providing a strong scientific foundation for further evaluation of combination regimens in this population.

The AIM-T study is designed to generate evidence on the efficacy, safety, and acceptability of albendazole-ivermectin combination therapies among schoolchildren living in La Moskitia, a highly endemic region in northeastern Honduras. The study will evaluate a novel fixed-dose combination formulation alongside currently available treatment approaches. In addition to measuring treatment outcomes, the study incorporates molecular diagnostics based on quantitative real-time polymerase chain reaction (qPCR), allowing highly sensitive detection of infections and quantitative assessment of parasite burden before and after treatment.

Participants with confirmed T. trichiura infection will receive a single-dose treatment regimen and will be followed for approximately three weeks. Treatment efficacy will be assessed through post-treatment stool examination using qPCR. Safety monitoring will include active, passive, and remote surveillance for adverse events following treatment. The study will also evaluate treatment acceptability among children and caregivers through structured questionnaires, generating evidence on user experience and preferences that may influence future implementation.

By combining efficacy, safety, and acceptability assessments, this study aims to generate evidence relevant to both clinical practice and public health programs. The findings are expected to inform policy decisions regarding the use of fixed-dose albendazole-ivermectin combinations in school-based and community-based deworming programs in Honduras and other STH-endemic settings. As the first evaluation of this fixed-dose combination in schoolchildren in the Americas, the study represents an important step in the pathway from clinical innovation to programmatic implementation. The results are expected to inform future community-based implementation studies and support the adoption of the intervention by national deworming programs in Honduras and, potentially, throughout the region.

Inclusion Criteria:

• Trichuris trichiura infection documented by quantitative real-time PCR (qPCR) performed within 30 days prior to randomization.
• Age 6 to 15 years inclusive.
• Written informed consent provided by a parent or legal guardian. Assent provided by children aged 9 years or older, according to local ethical requirements.

Exclusion Criteria:

• Known allergy or hypersensitivity to albendazole or ivermectin.
• Receipt of an anthelmintic treatment (albendazole, mebendazole, or ivermectin) within 3 months prior to enrollment.
• Participation in another clinical trial within 3 months prior to enrollment.
• Severe comorbidity at the investigator's discretion (e.g., diarrhea, tuberculosis, or malaria).
• Body weight <15 kg.
• Positive pregnancy test or refusal to undergo pregnancy testing in post-menarcheal girls and female adolescents of childbearing potential.