Efficacy and Safety of a Multi-dose Regimen of Mebendazole Against Hookworm in Children
Status:
Completed
Trial end date:
2017-09-15
Target enrollment:
Participant gender:
Summary
This study is a double-blind randomized clinical trial which aims at providing evidence on
the efficacy and safety of two regimens of mebendazole in school-aged children. Thus, our
primary objective is to assess the efficacy and safety of: i) 100 mg solid tablets twice a
day for 3 days, and ii) one dose of 500 mg solid tablets of mebendazole in participants aged
6-12, inclusive, infected with hookworm.
The primary endpoint of the trial is the cure rate (CR) of the 3-day regimen of mebendazole
against hookworm and a single dose mebendazole treatment.
The secondary objectives are to determine if the multi-dose regimen is superior to the single
dose regimen, evaluate the efficacy against concomitant soil-transmitted helminth infections,
and assess the safety of both mebendazole regimens.
After obtaining informed consent from children's caregiver, the medical history of the
participating individuals will be assessed with a standardized questionnaire, in addition to
a clinical examination carried out by the study physician on the treatment day. 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 apart. All stool samples will be examined with
duplicated Kato-Katz thick smears by experienced laboratory technicians.
Randomization of participants into the two treatment arms will be stratified according to
intensity of infection. Participants will be interviewed before treatment for clinical
symptoms and 3 hours after every morning treatment and 24 hours after every morning treatment
about the occurrence of adverse events. The efficacy of the treatment will be determined
14-21 days post-treatment by collecting another two stool samples.
The primary analysis will include all participants with primary end point data (available
case analysis). Supplementary, two sensitivity analyses will be conducted imputing all
missing endpoint data as treatment failures or all as treatment success. CRs will be
calculated as the percentage of egg-positive participants at baseline who become egg-negative
after treatment. CRs will be compared by using unadjusted logistic regression. To assess
model robustness with respect to covariates, adjusted logistic regressions (adjustment for
age, sex, school, weight and strata) will be performed.
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 ERRs and the
difference of the ERRs.