Mebendazole tablets which are produced by most pharmaceutical manufacturers, including the State Pharmaceutical Manufacturing Corporation (SPMC) of Sri Lanka, contain a mixture of polymorphs A and C. However, there is some evidence to show that mebendazole polymorph C is the only form effective against the soil-transmitted helminths. This protocol describes a stratified, randomized, placebo-controlled trial that examined the efficacy of different mebendazole polymorphs produced by the SPMC in the treatment of hookworm infections.

Comparative Efficacy of Different Mebendazole Polymorphs in the Treatment of Soil-transmitted Helminth Infections

Necator Americanus Infection

Mebendazole has three polymorphic forms, identified as A, B and C. All of them are in accord with the US Pharmacopeia specifications (USP XXI) but they have distinct physiochemical characteristics (Himmelreich et al, 1977) and different therapeutic activities in experimentally infected mice with Trichinella spiralis infections (Rodriguez-Caabeiro et al, 1987). The original mebendazole tablets which were used to treat human infections had more than 90% of polymorph C (Van den Bossche et al, 1982), but most pharmacopeias currently do not specify the proportion of polymorph C that a tablet of mebendazole should contain, and the assay specified for measurement of the active ingredient measures all polymorphs together. There is some evidence to show that unlike polymorph C, polymorph A is ineffective in the treatment of hookworm and whipworm infections (Charoenlarp et al, 1993). The State Pharmaceutical Manufacturing Corporation of Sri Lanka produces both 500 mg and 100 mg tablets of mebendazole according to specifications laid down in the US Pharmacopeia. These tablets contain a mixture of polymorphs A and C. It is possible that increasing the content of mebendazole polymorph C in single dose tablets may improve cure rates and egg reduction rates, especially against hookworm and whipworm infections, where much variation in efficacy has been observed.

Mebendazole polymorph A and C 500 mg

Mebendazole polymorph C

Placebo

Cure rate={(Number positive pretreatment - Number positive posttreatment)÷(Number positive pretreatment)}×100

Professor of Parasitology

FECR1= {[(Arithmetic mean of pretreatment egg counts)-(arithmetic mean of posttreatment egg counts)]÷(arithmetic mean of pretreatment egg counts)}×100

FECR2=〈Arithmetic mean {[(pretreatment egg count)-(posttreatment egg count)]÷(pretreatment egg count)}〉×100

Placebo tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka

Mebendazole tablets produced by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg of mebendazole as a 50:50 mixture of Polymorphs A and C

Mebendazole tablets manufactured by the State Pharmaceutical Manufacturing Corporation of Sri Lanka, containing 500mg dose of mebendazole as Polymorph C alone

Agalawatta Plantations PLC

Lellopitiya Estate, Hapugastenne Plantations PLC

Hookworm positive participants randomized to placebo

Hookworm positive participants randomized to a single dose of Mebendazole polymorph A and C 500 mg

Mebendazole Polymorph A and C 500 mg

Hookworm positive participants randomized to a single dose of Mebendazole polymorph C 500 mg

Mebendazole Polymorph C 500 mg

Total

Age, Categorical

Age Continuous

Sex: Female, Male

Sri Lanka

Region of Enrollment

All those found positive for hookworm infection, from among the population screened at baseline

Small sample size owing to limitation in available funds.

Dr Balachandran Kumarendran

Hookworm infected individual randomized to placebo

Hookworm infected individuals randomized to a single dose of Mebendazole polymorph A and C 500 mg

Hookworm infected individuals randomized to a single dose of Mebendazole polymorph C 500 mg

All participants who were hookworm positive at baseline, and who provided a faecal sample for examination at follow up.

Cure Rate

FECR1= {\[(Arithmetic mean of pretreatment egg counts)-(arithmetic mean of posttreatment egg counts)\]÷(arithmetic mean of pretreatment egg counts)}×100

Hookworm positive participants randomized to a single dose Mebendazole polymorph C 500 mg

All participants who were hookworm positive at baseline, and who provided a faecal sample for examination at follow-up, were included in the analysis

Faecal Egg Count Reduction 1 (FECR1)

FECR2=〈Arithmetic mean {\[(pretreatment egg count)-(posttreatment egg count)\]÷(pretreatment egg count)}〉×100

All participants who were hookworm positive at baseline, and who provided a faecal sample for examination at follow up were included in the analysis

Faecal Egg Count Reduction 2 (FECR2)

70 were allocated to this arm and 49 were followed up in the post treatment.

70 were allocated and 53 were followed up in the post treatment.

74 were allocated and 48 were followed up in the post treatment.

Comparative Efficacy of Different Mebendazole Polymorphs in the Treatment of Soil-transmitted Helminth Infections

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Trial Timing

What is this trial about?

What are the participation requirements?