Assessment of Drug Efficacy of Local Albendazole

Study Overview
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Brief Summary
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Infections with soil-transmitted helminthes (STH) occur throughout the developing world and remain a major public health problem in the poorest communities. Preventive chemotherapy (PC) programs in which single-dose albendazole 400 mg or single-dose mebendazole 500 mg - the drugs of choice for STH - are administered at the population level, is the main strategy for STH control. To ensure quality, these drugs are being widely donated by GlaxoSmithKline (GSK) (albendazole (ALB), Zentel) and Johnson & Johnson (mebendazole (MEB), Vermox). In addition to this, there are a wide variety of ALB and MEB tablets available on the local market. Although little is known about the quality of anthelmintics sold for human use, several publications have reported variability in the quality of generic anthelmintics used in veterinary medicine. The main objective of the present study is to compare the efficacy of two ALB brands bought on the local market, including OVIS (Korea, DAEHWA pharmaceutical) and BENDEX (India, Cipla)

Detailed Description
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Background Infections with soil-transmitted helminthes (STH) occur throughout the developing world and remain a major public health problem in the poorest communities. Infection is caused by four main species of worms commonly known as roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura) and hookworms (Ancylostoma duodenale and Necator americanus). It is estimated that STH affects more than 2 billion people worldwide, of which 450 million have significant morbidity attributable to their infection, and hence are one of the most important neglected tropical diseases. Children and pregnant women are the two most vulnerable groups. Children experience growth stunting and diminished physical fitness as well as impaired memory and cognition, resulting in impaired childhood educational performance and reduce school attendance; pregnant women suffer significant morbidity with hookworm-associated anemia likely contributing to maternal mortality. Preventive chemotherapy (PC) programs in which single-dose albendazole 400 mg or single-dose mebendazole 500 mg - the drugs of choice for STH - are administered at the population level, is the main strategy for STH control. To ensure quality, these drugs are being widely donated by GlaxoSmithKline (GSK) (albendazole (ALB), Zentel) and Johnson & Johnson (mebendazole (MEB), Vermox). In addition to this, there are a wide variety of ALB and MEB tablets available on the local market. Although little is known about the quality of anthelmintics sold for human use, several publications have reported variability in the quality of generic anthelmintics used in veterinary medicine. The concentrations of nine anthelmintic products (levamisol and MEB) purchased in pharmacies and from agricultural merchants in Kenya varied from 0 to 118 % of their claimed composition. Efficacy studies of seven brands of ALB against gastrointestinal nematodes in sheep in Ethiopia showed that the efficacy of only five of the seven brands was satisfactory. Objectives The main objective of the present study is to compare the efficacy of two ALB brands bought on the local market, including OVIS (Korea, DAEHWA pharmaceutical) and BENDEX (India, Cipla) Materials and methods 3.1. Study Population School children between 4 and 18 years old are the focus of this study because of two main reasons: school children are normally a major target for regular treatment with anthelminthic, because they are the group that usually has the heaviest worm burdens for A. lumbricoides and T. trichiura, and are steadily acquiring hookworm infections. In addition, they are in a period of intense physical and intellectual growth. Deworming schoolchildren has a considerable benefit on their nutritional status, physical fitness, appetite, growth and intellectual development. 3.2. Study design The study design is based on the recent WHO guidelines on how to assess drug efficacy against STH. Briefly, following obtaining informed consent, school children 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 fecal egg counts (FEC) for each STH present. For the initial sampling the aim is to enroll at least 650 children. This is based on a sample size of at least 50 infected subjects for each STH in each treatment arm (cfr WHO guidelines), an apparent prevalence of 20% for the least prevalent STH species and a drop out of 20%. All children providing stool samples will be randomized across two treatment arms. Fourteen days after treatment a second fecal 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. At follow-up all students will receive a single oral dose ALB tablet that was donated by GSK through WHO (Zentel). 3.3. Determination of FEC of STH All fecal samples will be processed using the McMaster egg counting technique (analytic sensitivity of 50 EPG) for the detection and the enumeration of infections with A. lumbricoides, T. trichiura and hookworms. 3.4. Statistical analysis The efficacy of the brands against each of the three STH will be measured by reduction in FEC using the formula below. The efficacy of the drugs will be classified into 'satisfactory', 'doubtful' and 'reduced' using the criteria summarized in Table 1. Table 1. The criteria based on FECR classifying efficacy of drugs into 'satisfactory', 'doubtful' and 'reduced' A. lumbricoides T. trichiura Hookworm Satisfactory FECR ≥ 95% FECR ≥ 50% FECR ≥ 90% Doubtful 95%> FECR ≥95% 50%> FECR ≥40% 90%> FECR ≥80% Reduced FECR ≤85% FECR ≤40% FECR ≤80% 3.5. Interpretation In any case of doubtful or reduced efficacy further steps will be taken to assess the efficacy of the drug. Ethical issues This study will be reviewed by the Ethics committees of the Faculty of Medicine, Ghent University (Belgium) and the Jimma University, Jimma (Ethiopia).

Official Title
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Assessment of Drug Efficacy of Albendazole Bought on Local Market Against Soil-transmitted Helminth Infections in School Children in Jimma, Ethiopia

Conditions
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Helminthiasis

Intervention / Treatment
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* Drug: albendazole BENDEX
* Drug: albendazole OVIS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 5-18 years old. Sex: males and females. Signed of written informed consent sheet by parents/or guardians, and those who volunteered to comply with study procedures (stool submission, drug treatment). Females: was not pregnant (as verbally assessed by clinician upon enrolled to treatment). Exclusion Criteria: Had vomit within 4 hours after drug administration. Had diarrhea at time of the first sampling. Subjects who were unable to provide a stool sample at follow-up, Subjects who experienced a severe concurrent medical condition Subjects with known history of allergic reaction to ALB.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ALB-BENDEX<br>albendazole, 400 mg, single oral dose, (BENDEX) | Drug: albendazole BENDEX<br>* randomized clinical trial with 2 parallel arms<br>* Other names: BENDEX/OVIS;|
| Active Comparator: ALB-OVIS<br>albendazole, 400 mg, single-oral dose, (OVIS) | Drug: albendazole OVIS<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Egg reduction rate |  | 14 days after administration of the drugs |