HookwormPhase 4NCT03245398
Efficacy and Safety of a Multi-dose Regimen of Mebendazole Against Hookworm in Children
A Phase 4 study testing Treatment with one of the two regimens of mebendazole in people with Hookworm, run by Jennifer Keiser at 1 site in Tanzania.
Trial summary
This study is a double-blind randomized clinical trial which aims at providing evidence on the efficacy and safety of two regimens of mebendazole in school-aged children. Thus, our primary objective is to assess the efficacy and safety of: i) 100 mg solid tablets twice a day for 3 days, and ii) one dose of 500 mg… Read more about this study
- Who is it for?
- Ages 6 to 12 years
- Conditions the study is for
- Hookworm
- What is being tested?
- Treatment with one of the two regimens of mebendazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 186 participants
- Where
- 1 siteTanzania
- Study dates
- 25 Jul 2017to 15 Sep 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Written informed consent signed by parents and/or caregiver; and oral assent by participant.
- Able and willing to be examined by a study physician at the beginning of the study.
- Able and willing to provide two stool samples at the beginning (baseline) and approximately three weeks after treatment (follow-up).
- Positive for hookworm eggs in the stool (≥ 100 EPG and at least two Kato-Katz thick smears slides with more than one hookworm egg).
- Absence of major systemic illnesses, e.g. diabetes, severe anemia (HB<8.0 g/l) as assessed by a medical doctor at school, upon initial clinical assessment.
- No known or reported history of chronical illness as cancer, diabetes, chronic heart, liver or renal disease.
- No recent anthelminthic treatment (within past 4 weeks). No known allergy to study medications (mebendazole and albendazole).
Who cannot join
- No written informed consent by parents and/or caregiver; no oral assent by participant.
- Menarche, based on self-report
- Presence of major systemic illnesses, e.g. diabetes, severe anemia (HB<8.0 g/l) as assessed by a medical doctor, upon initial clinical assessment.
- History of acute or severe chronic disease.
- Recent use of anthelminthic drug (within past 4 weeks).
- Attending other clinical trials during the study.
- Negative diagnostic result for hookworm eggs in the stool (< 100 EPG (total of the four slides) and/or only one Kato-Katz thick smear slide with more than one hookworm egg).
Trial locations and contacts
1 site in 1 country.
Tanzania1 site
Public Health Laboratory Ivo de Carneri, P.O. Box 122
Chake Chake, Pemba
About this study
Official title: Efficacy and Safety of a Single-dose Regimen and a Multi-dose Regimen of Mebendazole Against Hookworm Infections in School Children: a Randomized Controlled Trial
This study is a double-blind randomized clinical trial which aims at providing evidence on the efficacy and safety of two regimens of mebendazole in school-aged children. Thus, our primary objective is to assess the efficacy and safety of: i) 100 mg solid tablets twice a day for 3 days, and ii) one dose of 500 mg solid tablets of mebendazole in participants aged 6-12, inclusive, infected with hookworm.
The primary endpoint of the trial is the cure rate (CR) of the 3-day regimen of mebendazole against hookworm and a single dose mebendazole treatment.
Read more
The secondary objectives are to determine if the multi-dose regimen is superior to the single dose regimen, evaluate the efficacy against concomitant soil-transmitted helminth infections, and assess the safety of both mebendazole regimens.
After obtaining informed consent from children's caregiver, the medical history of the participating individuals will be assessed with a standardized questionnaire, in addition to a clinical examination carried out by the study physician on the treatment day. Enrollment will be based on two stool samples which will be collected, if possible, on two consecutive days or otherwise within a maximum of 5 days apart. All stool samples will be examined with duplicated Kato-Katz thick smears by experienced laboratory technicians.
Randomization of participants into the two treatment arms will be stratified according to intensity of infection. Participants will be interviewed before treatment for clinical symptoms and 3 hours after every morning treatment and 24 hours after every morning treatment about the occurrence of adverse events. The efficacy of the treatment will be determined 14-21 days post-treatment by collecting another two stool samples.
The primary analysis will include all participants with primary end point data (available case analysis). Supplementary, two sensitivity analyses will be conducted imputing all missing endpoint data as treatment failures or all as treatment success. CRs will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment. CRs will be compared by using unadjusted logistic regression. To assess model robustness with respect to covariates, adjusted logistic regressions (adjustment for age, sex, school, weight and strata) will be performed.
Geometric and arithmetic mean egg counts will be calculated for the different treatment arms before and after treatment to assess the corresponding ERRs. Bootstrap resampling method with 5,000 replicates will be used to calculate 95% confidence intervals (CIs) for ERRs and the difference of the ERRs.
- Conditions
- Hookworm
- Being tested
- Treatment with one of the two regimens of mebendazole
- Medical subject headings
- Ancylostomiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment with one of the two regimens of mebendazoleDrug
Once in the morning and once in the evening for 3 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| Single dose of mebendazole | Active comparator | In day 1 each child in this treatment arm will receive a 500 mg tablet of mebendazole plus one 100 mg placebo tablet in the morning. In the afternoon of day 1 they will only receive the placebo. In day 2 and 3 each child will receive one placebo twice a day (in the morning and in the evening) Receives: Drug: Treatment with one of the two regimens of mebendazole |
| Multiple dose of mebendazole | Active comparator | In day 1 each child in this treatment arm will receive a 100 mg tablet of mebendazole plus one 500 mg placebo tablet in the morning. In the afternoon of day 1 they will only receive the 100 mg tablet of mebendazole. In day 2 and 3 each child will receive one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Receives: Drug: Treatment with one of the two regimens of mebendazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline (before treatment) and 18 to 22 days post-treatment
Secondary outcomes (8)
Geometric Mean Egg Reduction Rate (ERR) of the Two Regimens 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).
Measured: baseline (before treatment) and 18 to 22 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.
Measured: baseline (before treatment) and 18 to 22 days post-treatment
Geometric ERR of Both Mebendazole Regimens 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).
Measured: baseline (before treatment) and 18 to 22 days post-treatment
Cure Rate (CR) of Both Mebendazole Regimens Against Ascaris Lumbricoides
Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.
Measured: baseline (before treatment) and 18 to 22 days post-treatment
Geometric ERR of Both Mebendazole Regimens 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).
Measured: baseline (before treatment) and 18 to 22 days post-treatment
Arithmetic ERR of the Two Regimens 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).
Measured: baseline (before treatment) and 18 to 22 days post-treatment
Arithmetic ERR of Both Mebendazole Regimens 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).
Measured: baseline (before treatment) and 18 to 22 days post-treatment
Arithmetic ERR of Both Mebendazole Regimens 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).
Measured: baseline (before treatment) and 18 to 22 days post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2017
- Study start25 Jul 2017
- Primary completion15 Sep 2017
- Study completion15 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HookwormStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 186 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jennifer Keiser
- Sponsor type
- University, hospital or other
- Collaborators
- PATH, Public Health Laboratory Ivo de Carneri
- Responsible party
- Sponsor-investigator, Jennifer Keiser, Swiss Tropical & Public Health Institute
- Investigators
- Jennifer Keiser, PhD, Principal investigator, Swiss Tropical & Public Health Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03245398
- Sponsor's protocol ID
- TRIPLEMEB_PEMBA
- Status last verified
- Mar 2019
- First submitted
- 22 Jul 2017
- Last updated
- 17 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Palmeirim MS, Ame SM, Ali SM, Hattendorf J, Keiser J. Efficacy and Safety of a Single Dose versus a Multiple Dose Regimen of Mebendazole against Hookworm Infections in Children: A Randomised, Double-blind Trial. EClinicalMedicine. 2018 Jul 11;1:7-13. doi: 10.1016/j.eclinm.2018.06.004. eCollection 2018 Jul.
PubMed 31193620
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of a Single-dose Regimen and a Multi-dose Regimen of Mebendazole Against Hookworm Infections in School Children: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03245398
- Acronym / sponsor ID
- TRIPLEMEB_PEMBA
- Conditions
- Hookworm
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 186 participants (actual)
- Lead sponsor
- Jennifer KeiserUniversity, hospital or other
- Collaborators
- PATH, Public Health Laboratory Ivo de Carneri
- Study start
- 25 Jul 2017 (actual)
- Primary completion
- 15 Sep 2017 (actual)
- Study completion
- 15 Sep 2017 (actual)
- First posted
- 10 Aug 2017 (actual)
- Results
- Posted 17 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a double-blind randomized clinical trial which aims at providing evidence on the efficacy and safety of two regimens of mebendazole in school-aged children. Thus, our primary objective is to assess the efficacy and safety of: i) 100 mg solid tablets twice a day for 3 days, and ii) one dose of 500 mg solid tablets of mebendazole in participants aged 6-12, inclusive, infected with hookworm.
The primary endpoint of the trial is the cure rate (CR) of the 3-day regimen of mebendazole against hookworm and a single dose mebendazole treatment.
The secondary objectives are to determine if the multi-dose regimen is superior to the single dose regimen, evaluate the efficacy against concomitant soil-transmitted helminth infections, and assess the safety of both mebendazole regimens.
After obtaining informed consent from children's caregiver, the medical history of the participating individuals will be assessed with a standardized questionnaire, in addition to a clinical examination carried out by the study physician on the treatment day. Enrollment will be based on two stool samples which will be collected, if possible, on two consecutive days or otherwise within a maximum of 5 days apart. All stool samples will be examined with duplicated Kato-Katz thick smears by experienced laboratory technicians.
Randomization of participants into the two treatment arms will be stratified according to intensity of infection. Participants will be interviewed before treatment for clinical symptoms and 3 hours after every morning treatment and 24 hours after every morning treatment about the occurrence of adverse events. The efficacy of the treatment will be determined 14-21 days post-treatment by collecting another two stool samples.
The primary analysis will include all participants with primary end point data (available case analysis). Supplementary, two sensitivity analyses will be conducted imputing all missing endpoint data as treatment failures or all as treatment success. CRs will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment. CRs will be compared by using unadjusted logistic regression. To assess model robustness with respect to covariates, adjusted logistic regressions (adjustment for age, sex, school, weight and strata) will be performed.
Geometric and arithmetic mean egg counts will be calculated for the different treatment arms before and after treatment to assess the corresponding ERRs. Bootstrap resampling method with 5,000 replicates will be used to calculate 95% confidence intervals (CIs) for ERRs and the difference of the ERRs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single dose of mebendazole | Active comparator | Drug: Treatment with one of the two regimens of mebendazoleIn day 1 each child in this treatment arm will receive a 500 mg tablet of mebendazole plus one 100 mg placebo tablet in the morning. In the afternoon of day 1 they will only receive the placebo. In day 2 and 3 each child will receive one placebo twice a day (in the morning and in the evening) |
| Multiple dose of mebendazole | Active comparator | Drug: Treatment with one of the two regimens of mebendazoleIn day 1 each child in this treatment arm will receive a 100 mg tablet of mebendazole plus one 500 mg placebo tablet in the morning. In the afternoon of day 1 they will only receive the 100 mg tablet of mebendazole. In day 2 and 3 each child will receive one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Written informed consent signed by parents and/or caregiver; and oral assent by participant.
- Able and willing to be examined by a study physician at the beginning of the study.
- Able and willing to provide two stool samples at the beginning (baseline) and approximately three weeks after treatment (follow-up).
- Positive for hookworm eggs in the stool (≥ 100 EPG and at least two Kato-Katz thick smears slides with more than one hookworm egg).
- Absence of major systemic illnesses, e.g. diabetes, severe anemia (HB<8.0 g/l) as assessed by a medical doctor at school, upon initial clinical assessment.
Key exclusion criteria (7 listed)
- No written informed consent by parents and/or caregiver; no oral assent by participant.
- Menarche, based on self-report
- Presence of major systemic illnesses, e.g. diabetes, severe anemia (HB<8.0 g/l) as assessed by a medical doctor, upon initial clinical assessment.
- History of acute or severe chronic disease.
- Recent use of anthelminthic drug (within past 4 weeks).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Treatment with one of the two regimens of mebendazoleOnce in the morning and once in the evening for 3 consecutive days | Drug | Multiple dose of mebendazole, Single dose of mebendazole |
Primary outcome
Cure Rate (CR) of Mebendazole Against Hookworm
Time frame: baseline (before treatment) and 18 to 22 days post-treatment
Cure rates (CRs) will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment.
8 secondary outcomes
Geometric Mean Egg Reduction Rate (ERR) of the Two Regimens of Mebendazole Against Hookworm
Time frame: baseline (before treatment) and 18 to 22 days post-treatment
CR of Both Mebendazole Regimens Against Trichuris Trichiura
Time frame: baseline (before treatment) and 18 to 22 days post-treatment
Geometric ERR of Both Mebendazole Regimens Against Trichuris Trichiura
Time frame: baseline (before treatment) and 18 to 22 days post-treatment
Cure Rate (CR) of Both Mebendazole Regimens Against Ascaris Lumbricoides
Time frame: baseline (before treatment) and 18 to 22 days post-treatment
Geometric ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides.
Time frame: baseline (before treatment) and 18 to 22 days post-treatment
Arithmetic ERR of the Two Regimens of Mebendazole Against Hookworm
Time frame: baseline (before treatment) and 18 to 22 days post-treatment
Arithmetic ERR of Both Mebendazole Regimens Against Trichuris Trichiura
Time frame: baseline (before treatment) and 18 to 22 days post-treatment
Arithmetic ERR of Both Mebendazole Regimens Against Ascaris Lumbricoides
Time frame: baseline (before treatment) and 18 to 22 days post-treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31193620Palmeirim MS, Ame SM, Ali SM, Hattendorf J, Keiser J. Efficacy and Safety of a Single Dose versus a Multiple Dose Regimen of Mebendazole against Hookworm Infections in Children: A Randomised, Double-blind Trial. EClinicalMedicine. 2018 Jul 11;1:7-13. doi: 10.1016/j.eclinm.2018.06.004. eCollection 2018 Jul.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Keiser, PhD principal investigator
Swiss Tropical & Public Health Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Treatment with one of the two regimens of mebendazole in people with Hookworm, run by Jennifer Keiser at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cure Rate (CR) of Mebendazole Against Hookworm (time frame: baseline (before treatment) and 18 to 22 days post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03245398, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2019.