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CompletedNCT03995680CHEW_MEB_PEMBAUpdated Jul 20, 2020Results posted

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

A Phase 2 interventional study of Mebendazole in Hookworm Infections, sponsored by Swiss Tropical & Public Health Institute. Completed at 1 site in Tanzania. Open to participants aged 3 Years to 12 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-07-20.

Sponsored by Swiss Tropical & Public Health Institute · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
397
Allocation
Randomized
Ages
3 Years to 12 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Hookworm Infections

Keywords

  • Mebendazole
  • Chewable tablet
  • Hookworm
  • Soil-transmitted helminths
  • Efficacy
  • Safety
  • Acceptability
03

Who can participate

Ages eligible
3 Years to 12 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
397 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugMebendazole

    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.

05

What researchers measure

Primary outcomes

  1. 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).

    Time frame: Baseline (before treatment) and sometime between 14 and 21 days post-treatment

Secondary outcomes

  1. 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.

    Time frame: Baseline (before treatment) and sometime between 14 and 21 days post-treatment

  2. 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.

    Time frame: Baseline (before treatment) and sometime between 14 and 21 days post-treatment

  3. 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).

    Time frame: Baseline (before treatment) and sometime between 14 and 21 days post-treatment

  4. 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.

    Time frame: Baseline (before treatment) and sometime between 14 and 21 days post-treatment

  5. 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).

    Time frame: Baseline (before treatment) and sometime between 14 and 21 days post-treatment

  6. 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).

    Time frame: Baseline (before treatment) and sometime between 14 and 21 days post-treatment

  7. 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).

    Time frame: Baseline (before treatment) and sometime between 14 and 21 days post-treatment

  8. 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).

    Time frame: Baseline (before treatment) and sometime between 14 and 21 days post-treatment

06

Results

Posted Jul 20, 2020

Participant flow

Participant flow — Overall Study
MilestoneChewable Tablet of MebendazoleSwallowable Tablet of Mebendazole
Started199198
Completed197196
Not completed22

Outcome measures

PrimaryGeometric 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).

Time frame:
Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Reported as:
Number · percentage change in hookworm egg counts
Geometric Mean Egg Reduction Rate (ERR) of the Two Formulations of Mebendazole Against Hookworm
percentage change in hookworm egg countsChewable Tablet of MebendazoleSwallowable Tablet of Mebendazole
Geometric Mean Egg Reduction Rate (ERR) of the Two Formulations of Mebendazole Against Hookworm68.5 (60.4 to 75.3)70.8 (63.5 to 76.7)
SecondaryCure 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.

Time frame:
Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Reported as:
Number · percentage of participants
Cure Rate (CR) of Mebendazole Against Hookworm
percentage of participantsChewable Tablet of MebendazoleSwallowable Tablet of Mebendazole
Cure Rate (CR) of Mebendazole Against Hookworm12.7 (8.4 to 18.2)11.2 (7.2 to 16.5)
SecondaryCR 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.

Time frame:
Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Reported as:
Number · percentage of participants
CR of Both Mebendazole Regimens Against Trichuris Trichiura
percentage of participantsChewable Tablet of MebendazoleSwallowable Tablet of Mebendazole
CR of Both Mebendazole Regimens Against Trichuris Trichiura9.87.3
SecondaryGeometric 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).

Time frame:
Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Reported as:
Number · percentage change in T. trich egg counts
Geometric ERR of Both Mebendazole Formulations Against Trichuris Trichiura
percentage change in T. trich egg countsChewable Tablet of MebendazoleSwallowable Tablet of Mebendazole
Geometric ERR of Both Mebendazole Formulations Against Trichuris Trichiura73.3 (65.7 to 79.4)74.2 (67.2 to 79.8)
SecondaryCR 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.

Time frame:
Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Reported as:
Number · percentage of participants
CR of Both Mebendazole Formulations Against Ascaris Lumbricoides
percentage of participantsChewable Tablet of MebendazoleSwallowable Tablet of Mebendazole
CR of Both Mebendazole Formulations Against Ascaris Lumbricoides95.397.8
SecondaryGeometric 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).

Time frame:
Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Reported as:
Number · percentage change in A. lumbr egg counts
Geometric ERR of Both Mebendazole Formulations Against Ascaris Lumbricoides.
percentage change in A. lumbr egg countsChewable Tablet of MebendazoleSwallowable Tablet of Mebendazole
Geometric ERR of Both Mebendazole Formulations Against Ascaris Lumbricoides.99.999.9
SecondaryArithmetic 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).

Time frame:
Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Reported as:
Number · percentage change in hookworm egg counts
Arithmetic ERR of the Two Formulations of Mebendazole Against Hookworm
percentage change in hookworm egg countsChewable Tablet of MebendazoleSwallowable Tablet of Mebendazole
Arithmetic ERR of the Two Formulations of Mebendazole Against Hookworm38.2 (26.6 to 47.8)28.1 (8.5 to 44.3)
SecondaryArithmetic 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).

Time frame:
Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Reported as:
Number · percentage change in T. trich egg counts
Arithmetic ERR of Both Mebendazole Formulations Against Trichuris Trichiura
percentage change in T. trich egg countsChewable Tablet of MebendazoleSwallowable Tablet of Mebendazole
Arithmetic ERR of Both Mebendazole Formulations Against Trichuris Trichiura52.950.9
SecondaryArithmetic 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).

Time frame:
Baseline (before treatment) and sometime between 14 and 21 days post-treatment
Reported as:
Number · percentage change in A. lumbr egg counts
Arithmetic ERR of Both Mebendazole Formulations Against Ascaris Lumbricoides
percentage change in A. lumbr egg countsChewable Tablet of MebendazoleSwallowable Tablet of Mebendazole
Arithmetic ERR of Both Mebendazole Formulations Against Ascaris Lumbricoides98.799.8
Statistical analysis
  • Chewable Tablet of Mebendazole vs Swallowable Tablet of Mebendazole · Regression, Logistic · Difference in egg reduction rate (%): 2.3 · 95% CI -7.8 to 12.6Adjusted for age, sex, weight and baseline hookworm infection intensity (light or moderate/heavy)

Adverse events

Collected over 3 hours and 24 hours post-treatment. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Chewable Tablet of Mebendazole0/197 (0%)0/197 (0%)14/197 (7.1%)
Swallowable Tablet of Mebendazole0/196 (0%)0/196 (0%)15/196 (7.7%)
Most frequent other events
Most frequent other events
EventChewable Tablet of MebendazoleSwallowable Tablet of Mebendazole
Abdominal painGeneral disorders14/19715/196

Baseline characteristics

Age, Continuous
Age, Continuous(years)Chewable Tablet of MebendazoleSwallowable Tablet of MebendazoleTotal
Mean9.3 ± 2.09.4 ± 2.19.3 ± 2.1
Sex: Female, Male
Sex: Female, Male(Participants)Chewable Tablet of MebendazoleSwallowable Tablet of MebendazoleTotal
Female8780167
Male110116226
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Chewable Tablet of MebendazoleSwallowable Tablet of MebendazoleTotal
Count of participants——0
Height
Height(centimeters)Chewable Tablet of MebendazoleSwallowable Tablet of MebendazoleTotal
Mean130.5 ± 11.5130.8 ± 11.6130.7 ± 11.6
Weight
Weight(kilograms)Chewable Tablet of MebendazoleSwallowable Tablet of MebendazoleTotal
Mean25.4 ± 6.326.0 ± 6.625.7 ± 6.5
Hemoglobin
Hemoglobin(grams per liter)Chewable Tablet of MebendazoleSwallowable Tablet of MebendazoleTotal
Mean121.5 ± 10.3123.5 ± 10.7122.5 ± 10.5
07

Study locations

1 site
  • Public Health Laboratory Ivo de Carneri
    Chake Chake, Tanzania
08

References and documents

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. PubMed 33150325 ↗

Study documents

  • Protocol and statistical analysis plan · Aug 26, 2019
  • Informed consent form · Dec 24, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03995680
Lead sponsor
Swiss Tropical & Public Health Institute
Collaborators
Public Health Laboratory Ivo de Carneri
Responsible party
Jennifer Keiser (Prof. Dr., Swiss Tropical & Public Health Institute) — Principal investigator
First posted
Jun 24, 2019
Start date
Jul 12, 2019
Primary completion
Oct 9, 2019
Completion
Oct 9, 2019
Results posted
Jul 20, 2020
Last update
Jul 20, 2020

Study contacts

Jennifer Keiser, PhD
principal investigator · Swiss Tropical & Public Health Institute

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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