Assessment of Drug Efficacy of Local Albendazole
Condition: Helminthiasis
MeSH terms: Helminthiasis
Study type: Interventional

Summary: 
      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: 
      1. 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.

        2. 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)

        3. 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.

        4. 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).
    

Intervention name(s): albendazole BENDEX; albendazole OVIS
Intervention type(s): Drug; Drug
Intervention description(s): randomized clinical trial with 2 parallel arms
Other intervention name(s): BENDEX/OVIS
Intervention MeSH terms: Albendazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention