In view that efficacy of co-administered ivermectin (IVM) and albendazole (ALB) has been found to vary between different settings the rationale of this parallel open-label randomized controlled superiority trial is to provide evidence on the efficacy of co-administered ivermectin and albendazole compared to albendazole monotherapy in school-aged children aged 6-12 years against infection with T. trichiura in Uganda.
Our primary objective is to demonstrate superiority of
1. Arm A: single dose of ivermectin (200 µg/kg, 3 mg tablets according to weight) / single dose of albendazole (400 mg tablet) combination, compared to
2. Arm B: single dose of albendazole (400 mg tablet)
in terms of cure rate (CR) against T. trichiura infections in school-aged children aged 6-12 years assessed at 14-21 days post-treatment by Kato-Katz microscopy.
The secondary objectives of the trial are:
1. to determine the egg reduction rates (ERRs) of ivermectin/albendazole combination therapy compared to albendazole monotherapy against T. trichiura
2. to determine the CRs and ERRs of the study drugs against Ascaris lumbricoides and hookworm in co-infected participants
3. to evaluate the safety and tolerability of the treatment
The study will be implemented as a school-based study and children aged 6-12 years from two primary schools in Kabale district, southwestern Uganda will be invited for parasitological examination after obtaining informed consent from parents/caregivers and assent by the minor participants. Two stool samples will be collected, when possible, on two consecutive days. Children found to be infected with T. trichiura based on quadruplicate Kato-Katz thick smear readings will be enrolled into the actual trial. The medical history of the participants will be assessed with a standardized questionnaire, in addition to a clinical examination carried out by the study nurse/physician before treatment.
All participants will be interviewed before treatment and after 3 and 24 hours (active surveillance) for the occurrence of adverse events (AEs). Participants and their caregivers will be told that any potential AEs happening between 24 hours and the respective follow-up time point for stool collection should be reported to the local village health team (VHT) members, which will be trained to handle the situation by taking the participant to a health facility for timely treatment, or to local health workers directly.
The efficacy of the treatment will be determined at 14-21 days post-treatment by collecting another two stool samples.
At both, baseline and follow-up (14-21 days post treatment) a portion of stool (1.5-2 g) from all participants identified with T. trichiura infections will be preserved in 95% ethanol, shipped to a reference laboratory in Switzerland and subjected to amplicon deep sequencing for characterization of T. trichiura strains and investigation of potential resistance markers.
Study participants eligible for treatment will be randomly assigned to one of the two treatment arms stratified by 2 levels of baseline infection intensity (light: 1-999 EPG, and moderate plus heavy: ≥ 1000 EPG T. trichiura infections).
The primary analysis will include all participants with primary end point data (available case analysis). Supplementary, a per-protocol analysis will be conducted. CRs will be calculated as the percentage of egg-positive subjects at baseline who become egg-negative after treatment. Differences among CRs (between treatment arms) will be analyzed by using crude and adjusted logistic regression modeling.
Geometric and arithmetic mean egg counts will be calculated for the different treatment arms before and after treatment to assess the corresponding ERRs. Bootstrap resampling method with 5,000 replicates will be used to calculate 95% confidence intervals (CIs) for differences in ERRs.
