Efficacy and Safety of a New Chewable Versus the Swallowable Tablet of Mebendazole Against Hookworm

• Mebendazole (Drug): Treatment with one of the two formulations of mebendazole. The only difference between both arms is the type of formulation of the drug: chewable versus swallowable tablet.

Primary outcomes

• Geometric Mean Egg Reduction Rate (ERR) of the Two Formulations of Mebendazole Against Hookworm [Baseline (before treatment) and sometime between 14 and 21 days post-treatment]: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).

Secondary outcomes

• Cure Rate (CR) of Mebendazole Against Hookworm [Baseline (before treatment) and sometime between 14 and 21 days post-treatment]: Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.
• CR of Both Mebendazole Regimens Against Trichuris Trichiura [Baseline (before treatment) and sometime between 14 and 21 days post-treatment]: Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.
• Geometric ERR of Both Mebendazole Formulations Against Trichuris Trichiura [Baseline (before treatment) and sometime between 14 and 21 days post-treatment]: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).
• CR of Both Mebendazole Formulations Against Ascaris Lumbricoides [Baseline (before treatment) and sometime between 14 and 21 days post-treatment]: Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.
• Geometric ERR of Both Mebendazole Formulations Against Ascaris Lumbricoides. [Baseline (before treatment) and sometime between 14 and 21 days post-treatment]: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).
• Arithmetic ERR of the Two Formulations of Mebendazole Against Hookworm [Baseline (before treatment) and sometime between 14 and 21 days post-treatment]: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).
• Arithmetic ERR of Both Mebendazole Formulations Against Trichuris Trichiura [Baseline (before treatment) and sometime between 14 and 21 days post-treatment]: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).
• Arithmetic ERR of Both Mebendazole Formulations Against Ascaris Lumbricoides [Baseline (before treatment) and sometime between 14 and 21 days post-treatment]: Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(arithmetic mean EPG at follow-up/arithmetic mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (arithmetic mean at follow-up/arithmetic mean at baseline)*100).

Sex: All, ages: 3 Years to 12 Years, accepts healthy volunteers

Inclusion Criteria:

* Male or female children aged between 3 and 12 years;
* Written informed consent signed by caregiver;
* Was examined by a study physician before treatment;
* Provided two stool samples at baseline;
* Hookworm EPG > 100 and at least two Kato-Katz thick smears slides with more than one hookworm egg;

Exclusion Criteria:

* Pregnant;
* Presence or history of major systemic or chronic illnesses, as assessed by a medical doctor, such as can upon initial clinical assessment;
* Suffers from severe anemia (Hb < 80 g/l);
* Received anthelminthic treatment or metronidazole within past four weeks.
* Attending other clinical trials during the study.

Participant flow

Outcome results

• Geometric Mean Egg Reduction Rate (ERR) of the Two Formulations of Mebendazole Against Hookworm (Primary), Number, percentage change in hookworm egg counts: Chewable Tablet of Mebendazole 68.5 (60.4 to 75.3); Swallowable Tablet of Mebendazole 70.8 (63.5 to 76.7)
• Cure Rate (CR) of Mebendazole Against Hookworm (Secondary), Number, percentage of participants: Chewable Tablet of Mebendazole 12.7 (8.4 to 18.2); Swallowable Tablet of Mebendazole 11.2 (7.2 to 16.5)
• CR of Both Mebendazole Regimens Against Trichuris Trichiura (Secondary), Number, percentage of participants: Chewable Tablet of Mebendazole 9.8; Swallowable Tablet of Mebendazole 7.3
• Geometric ERR of Both Mebendazole Formulations Against Trichuris Trichiura (Secondary), Number, percentage change in T. trich egg counts: Chewable Tablet of Mebendazole 73.3 (65.7 to 79.4); Swallowable Tablet of Mebendazole 74.2 (67.2 to 79.8)
• CR of Both Mebendazole Formulations Against Ascaris Lumbricoides (Secondary), Number, percentage of participants: Chewable Tablet of Mebendazole 95.3; Swallowable Tablet of Mebendazole 97.8
• Geometric ERR of Both Mebendazole Formulations Against Ascaris Lumbricoides. (Secondary), Number, percentage change in A. lumbr egg counts: Chewable Tablet of Mebendazole 99.9; Swallowable Tablet of Mebendazole 99.9
• Arithmetic ERR of the Two Formulations of Mebendazole Against Hookworm (Secondary), Number, percentage change in hookworm egg counts: Chewable Tablet of Mebendazole 38.2 (26.6 to 47.8); Swallowable Tablet of Mebendazole 28.1 (8.5 to 44.3)
• Arithmetic ERR of Both Mebendazole Formulations Against Trichuris Trichiura (Secondary), Number, percentage change in T. trich egg counts: Chewable Tablet of Mebendazole 52.9; Swallowable Tablet of Mebendazole 50.9
• Arithmetic ERR of Both Mebendazole Formulations Against Ascaris Lumbricoides (Secondary), Number, percentage change in A. lumbr egg counts: Chewable Tablet of Mebendazole 98.7; Swallowable Tablet of Mebendazole 99.8

Adverse events

Time frame: 3 hours and 24 hours post-treatment

Other adverse events by term

• Results publication: Palmeirim MS, Bosch F, Ame SM, Ali SM, Hattendorf J, Keiser J. Efficacy, safety and acceptability of a new chewable formulation versus the solid tablet of mebendazole against hookworm infections in children: An open-label, randomized controlled trial. EClinicalMedicine. 2020 Sep 20;27:100556. doi: 10.1016/j.eclinm.2020.100556. eCollection 2020 Oct. PMID 33150325

• Study Protocol and Statistical Analysis Plan (PDF, 2019-08-26)
• Informed Consent Form (PDF, 2018-12-24)

• Jennifer Keiser, PhD, Principal investigator, Swiss Tropical & Public Health Institute