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

Efficacy and Safety of a New Chewable Tablet of Mebendazole Versus the Swallowable, Standard Tablet of Mebendazole Against Hookworm Infections in Children: a Randomized Controlled Trial

The rational of this study is to provide evidence on the safety and efficacy of a new chewable tablet of mebendazole compared to the standard tablet in preschool- and school-aged children infected with hookworm.

Study Overview

• Status: Completed
• Conditions: Hookworm Infections
• Intervention / Treatment: Drug: Mebendazole

• Study Type: Interventional
• Enrollment (Actual): 397
• Phase: Phase 2

Contacts and Locations

Study Locations

• Tanzania
  • Chake Chake, Tanzania
    • Public Health Laboratory Ivo de Carneri

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Chewable tablet of mebendazole; 3-5 year olds allocated to the swallowable tablet arm will be given the crushed tablet on a spoon mixed with a small amount of clean water;; 6-12 year olds allocated to the swallowable tablet arm will be given the whole tablet to swallow with a glass of clean water;	Drug: Mebendazole; 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.
ACTIVE_COMPARATOR: Swallowable tablet of mebendazole; 3-5 year olds allocated to the chewable tablet arm will be encouraged to chew the tablet and swallow it without water; if they cannot chew it then a small amount of water will be added to the tablet in a spoon;; 6-12 year olds allocated to the chewable tablet arm will be encouraged to chew the tablet and then swallow it without water.	Drug: Mebendazole; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Egg Reduction Rate (ERR) of the Two Formulations of Mebendazole Against Hookworm	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).	Baseline (before treatment) and sometime between 14 and 21 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure Rate (CR) of Mebendazole Against Hookworm	Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.	Baseline (before treatment) and sometime between 14 and 21 days post-treatment
CR of Both Mebendazole Regimens Against Trichuris Trichiura	Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.	Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Geometric ERR of Both Mebendazole Formulations Against Trichuris Trichiura	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).	Baseline (before treatment) and sometime between 14 and 21 days post-treatment
CR of Both Mebendazole Formulations Against Ascaris Lumbricoides	Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.	Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Geometric ERR of Both Mebendazole Formulations Against Ascaris Lumbricoides.	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).	Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Arithmetic ERR of the Two Formulations of Mebendazole Against Hookworm	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).	Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Arithmetic ERR of Both Mebendazole Formulations Against Trichuris Trichiura	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).	Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Arithmetic ERR of Both Mebendazole Formulations Against Ascaris Lumbricoides	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).	Baseline (before treatment) and sometime between 14 and 21 days post-treatment

Collaborators and Investigators

• Sponsor: Swiss Tropical & Public Health Institute
• Collaborators: Public Health Laboratory Ivo de Carneri

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 12, 2019
• Primary Completion (ACTUAL): October 9, 2019
• Study Completion (ACTUAL): October 9, 2019

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: June 21, 2019
• First Posted (ACTUAL): June 24, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 20, 2020
• Last Update Submitted That Met QC Criteria: July 17, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Hookworm; Mebendazole; Acceptability; Soil-transmitted helminths; Chewable tablet
• Additional Relevant MeSH Terms: Parasitic Diseases; Secernentea Infections; Nematode Infections; Helminthiasis; Strongylida Infections; Infections; Hookworm Infections; Ancylostomiasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Mebendazole; Piperazine; Piperazine citrate; DMP 777
• Other Study ID Numbers: CHEW_MEB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes