Clinical trial NCT01379326: Monitoring the Efficacy of Anthelmintics for the Treatment of Soil Transmitted Helminths P2
Official title: The Efficacy of a Single-dose Mebendazole Against Soil-transmitted Helminths in School Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ascaris Lumbricoides
Ascaris Suum
Trichuris Trichiura
Trichuris Vulpis
Ancylostoma Duodenal
Ancylostoma Caninum
Ancylostoma Ceylanicum
Necator Americanus
Lead sponsor: University Ghent
Sponsor class: OTHER
Collaborators: name: Commonwealth Scientific and Industrial Research Organisation, Australia
name: World Health Organization
name: Institut Pasteur, Cambodia
name: The University of Queensland
name: Oswaldo Cruz Foundation
name: University of Nottingham
name: University of Yaounde 1
name: Ivo de Carneri, Pemba Island, Tanzania
name: National Institute of Malariology, Parasitology and Entomology, Vietnam
name: Jimma University
name: Fundación Huésped
name: Queensland Institute of Medical Research
name: Institut Pasteur
First posted: 2011-06-23
Enrollment: 250
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Objectives:

The overall objective is to monitor efficacy of mebendazole (MBZ) against Soil-Transmitted Helminths (STH).

The primary objective is:

(1) to monitor the efficacy a single dose 500 mg of mebendazole (MBZ) against Soil-Transmitted Helminths (STH) infections by means of Faecal Egg Count Reduction (FECR) and Cure Rate (CR).

The secondary objectives are:

1. to assess the occurrence of Necator americanus and Ancylostoma duodenal.
2. to assess the occurrence of β-tubulin mutations related to resistance before and after drug administration.
3. to evaluate the role of dogs and pigs as reservoir for zoonotic transmission.

Detailed description: Primary objective:

Following obtaining informed consent, schoolchildren in the target age range group will be recruited and asked to provide a recent stool sample (an interval of less than 4 hours) that will be processed to determine the Faecal Egg Count (FEC) for each Soil-Transmitted Helminths (STH) present. For the initial sampling the aim is to enroll at least 250 infected children for at least one of the Soil-Transmitted Helminths (STH). This sample size was selected based on statistical analysis of study power, using random simulations of correlated over-dispersed Faecal Egg Count data reflecting the variance-covariance structure in a selection of real Faecal Egg Count (FEC) data sets. This analysis suggested that a sample size of up to 200 individuals (α = 0.05, power = 80%) was required to detect a 10 percentage point drop from a null efficacy of \~ 80% (mean percentage FEC ∆ per individual) over a wide range of infection scenarios. Standard power analyses for proportions also indicated that the detection of a \~10 percentage point drop from a null cure rate required sample sizes up to 200 (the largest samples being required to detect departures from null efficacies of around 50%). Given an anticipated non-compliance rate of 25%, a sample of 250 infected subjects was therefore considered necessary at each study site.

All children providing stool samples will be treated with mebendazole (MBZ) single table of 500mg under supervision (chewing + water). The mebendazole (MBZ) will be provided (free) by the coordinating group. Seven up to fourteen days (maximum interval) after treatment a second faecal sample will be collected from the children to determine again FEC. Subjects who are unable to provide a stool sample at follow-up, or who are experiencing a severe concurrent medical condition or have diarrhea at time of the first sampling, will be excluded from the study.

Secondary objectives:

In 5 study sites, faecal samples of 100 infected subjects should be preserved before treatment with mebendazole (MBZ) in one tube (1 gram in 10 ml 70% ethanol). Samples of the same children should be also preserved again in one tube (1 gram in 10 ml 70% ethanol) after treatment. Samples have be send to the Laboratory of Parasitology, Ghent University.

The samples, collected before and after treatment will be subsequently examined by molecular assays the occurrence Necator americanus/Ancylostoma duodenal and the occurrence of β-tubulin mutations related to resistance.

The samples collected before treatment will be subsequently examined by molecular assays to assess the role of animals as a reservoir for human Soil-Transmitted Helminths (STH).

Parasitological techniques, determination of Faecal Egg Count of Soil-Transmitted Helminths (STH). All fecal samples were processed using the McMaster egg counting technique for the detection and the enumeration of infections with A. lumbricoides, T. trichiura and hookworms. All study sites are familiar with the technique and McMaster slides were provided previously.

Molecular assays (Laboratory of Parasitology, Ghent University)and Deoxyribonucleic acid (DNA) extraction.

DNA of Soil-Transmitted Helminths (STH) will be extracted from the samples preserved in ethanol 70% using the Qiagen mini stool kit.

Molecular identification of Soil-Transmitted Helminths (STH). The presence of the Soil-Transmitted Helminths species: Ascaris (n= 2), Trichuris (n = 2) and hookworms (n = 4) will be assessed using different molecular assays. For the differentiation of Trichuris species, species-specific polymerase chain reaction (PCR) will be applied. For the differentiation of Ascaris and the canine hookworms a PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) will be used. For the human hookworms, a quantitative PCR will be applied.

Presence of mutations in β-tubulin related to mebendazole (MBZ) resistance This specific objective will be performed in collaboration with McGill University (Canada).

Statistical analysis. Both Cure Rate (CR) and Faecal Egg Count Reduction (FECR) will be considered to monitor to efficacy of mebendazole (MBZ) against Soil-Transmitted Helminths. The statistical analysis will be assessed as described by Vercruysse et al., 2011.

Eligibility criteria: Exclusion Criteria:

* Subjects who are unable to provide a stool sample at follow-up
* Subjects who are experiencing a severe concurrent medical condition
* Subjects with diarrhea at first sampling

Primary outcomes:
measure: Reduction of fecal egg counts at 14 days post-intervention.
timeFrame: At 14 days post-intervention.
Secondary outcomes:
measure: Distribution of hookworms species.
timeFrame: Samples will be collected at 14 days of follow-up.
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Fundacion Huesped
city: Brisbane
country: Australia
facility: Commonwealth Scientific and Industrial Research Organisation
city: Herston QLD
country: Australia
facility: Queensland Institute for Medical Research, University of Queensland
city: Belo Horizonte
country: Brazil
facility: Fundação Oswaldo Cruz
city: Phnom Penh
country: Cambodia
facility: Institut Pasteur in Cambodia, Clinical Pathology Unit
city: Yaoundé I
country: Cameroon
facility: University of Yaoundé I
city: Jimma
country: Ethiopia
facility: College of Public Health and Medical Sciences, Jimma University
city: Zanzibar
country: Tanzania
facility: Ivo de Carneri, Pemba Island
city: Hanoi
country: Vietnam
facility: National Institute for Malariology, Parasitology and Entomology
Study officials:
References:
citation: Levecke B, Montresor A, Albonico M, Ame SM, Behnke JM, Bethony JM, Noumedem CD, Engels D, Guillard B, Kotze AC, Krolewiecki AJ, McCarthy JS, Mekonnen Z, Periago MV, Sopheak H, Tchuem-Tchuente LA, Duong TT, Huong NT, Zeynudin A, Vercruysse J. Assessment of anthelmintic efficacy of mebendazole in school children in six countries where soil-transmitted helminths are endemic. PLoS Negl Trop Dis. 2014 Oct 9;8(10):e3204. doi: 10.1371/journal.pntd.0003204. eCollection 2014 Oct.