- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03261596
Mebendazole Study Against Hookworm Infections in Children and Adolescents in Ghana
November 15, 2017 updated by: PATH
Efficacy and Safety of a Single-dose Regimen and a Multi-dose Regimen of Mebendazole Against Hookworm Infections in Children and Adolescents in Ghana: a Randomized Controlled Trial
The Ghana study will hypothesize that both the multiple dose and single dose of mebendazole will achieve effective cure rates against hookworm among children and adolescents.
This study is intended to be a pilot study for a planned Phase 3 registration trial of a new drug for hookworm, tribendimidine.
Study Overview
Detailed Description
This study will determine the Cure Rates (CRs) of mebendazole regimens to be used as comparator drug regimens in the future pivotal trial of tribendimidine and will provide evidence of the efficacy and safety of mebendazole among children and adolescents infected with hookworm in Ghana.
Children and adolescents bear a large burden of morbidity from hookworm infection, so building the evidence base for effective treatments in this population has important public health implications in Ghana and other endemic settings.
Study Type
Interventional
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Accra
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Legon, Accra, Ghana
- Noguchi Memorial Institute for Medical Research - University of Ghana
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
6 years to 18 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria
All participants must meet all of the following inclusion criteria:
- Male or female, aged 6 to 18 years, inclusive, at the time of randomization.
- Written informed consent signed by at least one parent and/or legally acceptable representative (as defined by local law); and assent by participant.
- Able and willing to be examined by a study health care provider at the beginning of the study.
- Able and willing to provide one stool sample at the beginning (baseline) and one sample approximately three weeks after treatment (follow-up).
- Positive for hookworm eggs in the stool (two Kato-Katz thick smear slides with more than one hookworm egg) at baseline.
Exclusion Criteria
Participants must meet none of the following exclusion criteria to be eligible for this study:
- Presence of major systemic illnesses as assessed by a study health care provider, upon initial targeted clinical assessment.
- Pregnancy, based on a positive urine rapid test, or breastfeeding in girls after menarche.
- Recent use of an anthelminthic drug (within the past 4 weeks) or use of anthelminthics not provided by study staff during the study period.
- Known allergy to mebendazole or albendazole.
- Participation in other clinical trials during the study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 100 mg solid tablets 2x/day for 3 days
Assess the efficacy (Cure Rate/CR) and safety of 100 mg dose regimen of mebendazole in children aged 6 to 18 years, inclusive, infected with hookworm.
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Participants will be randomized using a 1:1 ratio to one of the two arms.
Study participants eligible for treatment will be randomly assigned to one of the two treatment arms using a computer-generated stratified block randomization code.
Other Names:
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Experimental: Single dose 500 mg solid tablets
Assess the efficacy (Cure Rate/CR) and safety of 500 mg dose regimen of mebendazole in children aged 6 to 18 years, inclusive, infected with hookworm.
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Participants will be randomized using a 1:1 ratio to one of the two arms.
Study participants eligible for treatment will be randomly assigned to one of the two treatment arms using a computer-generated stratified block randomization code.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cure Rate (CR) against hookworm, as determined by Kato Katz.
Time Frame: 20 days
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To determine point estimates for the efficacy of two mebendazole regimens: (i) 100 mg solid tablets twice daily for three days, and (ii) single dose of 500 mg solid tablets in participants aged 6 to 18 years infected with hookworm.
The CR will be calculated as the percentage of children and adolescents (all hookworm egg-positive at enrollment) who are egg negative 20 days after treatment.
The CRs will be tabulated by mebendazole dose regimen received, along with their corresponding 95% CIs.
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20 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Egg reduction rate (ERR), based on geometric mean, against hookworm
Time Frame: 20 days
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In a simple analysis, the study will estimate a risk ratio between CRs by using log binomial regression.
Baseline characteristics will be assessed by arm to determine any imbalance between the two randomization arms.
Any factor (e.g., age, sex, school, weight, height, baseline hookworm infection intensity) out of balance at baseline will be adjusted for in the analyses.
Sensitivity analyses will be conducted which will consider all participants with missing endpoint data as treatment failure or all as treatment success to test whether the results (of the CR comparison) are sensitive to potential differences in loss to follow-up.
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20 days
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CR and ERR against Ascaris lumbricoides and Trichuris trichiura
Time Frame: 20 days
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Determine the ERR in the two treatment arms; EPG will be assessed by adding up the egg counts from the Kato-Katz thick smears and multiplying this number by twenty-four.
The ERR will be calculated (ERR = (1-(mean egg count at follow-up/mean egg count at baseline))*100).
Geometric mean egg counts will be calculated for the different treatment arms before and after treatment to assess the corresponding ERRs.
The bootstrap resampling method with 5,000 replicates will be used to calculate 95% CIs for ERRs and the difference between the ERRs.
Analyses of mebendazole efficacy against concomitant STHs will proceed similarly to those conducted for hookworm.
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20 days
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Adverse Events
Time Frame: Through 20 days of follow-up
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For the safety objective, the probability of observing zero, one or more, and two or more solicited AEs among the 150 subjects in each treatment arm given a true event rate.
For example, if the true rate of an AE among subjects receiving single dose mebendazole is 1% then the probability we will see 1 or more subjects with this event is 78%.
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Through 20 days of follow-up
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sensitivity of Kato-Katz and PCR for hookworm infection detection
Time Frame: Up to 14 weeks following Day 20
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Compare the sensitivity of Kato-Katz to quantitative polymerase chain reaction (PCR) assays among participants at day 20 of follow-up.
As there is no true gold standard for hookworm diagnosis, we will consider individuals as "true" positives if they are identified as positive by PCR or Kato-Katz.
This assumes no false positives for either diagnostic technique.
While PCR has higher sensitivity than microscopy in general, microscopy has been noted to have high specificity.
The study will therefore avoid discounting as "true" positives those who test negative by PCR but positive by microscopy and conduct an inter-method reliability study to separately compare hookworm and other STH diagnoses by PCR or the pooled microscopy in the full sample (N= 300) with the pooled (Kato-Katz or PCR positive) gold standard.
Specificity cannot be calculated, as both diagnostic methods are contained within the pooled gold standard.
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Up to 14 weeks following Day 20
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Prevalence of hookworm genetic resistance markers
Time Frame: Up to 14 weeks following Day 20
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Determine the prevalence of hookworm genetic resistance markers among participants at day 20 of follow-up.
The conditional prevalence is defined as the proportion of individuals who have a disease subtype among those who test positive for the disease.
All participants identified as positive for hookworm by PCR at day 20 will be considered hookworm positive.
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Up to 14 weeks following Day 20
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Distribution of hookworm species among participants
Time Frame: Up to 14 weeks following Day 20
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Determine the distribution of hookworm species among participants at baseline.
All participants identified as positive for hookworm by PCR at baseline will be considered hookworm positive.
The conditional prevalence(s) will be calculated as follows, pooled and separately for each arm.
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Up to 14 weeks following Day 20
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael Cappello, MD, Yale University
- Principal Investigator: Michael Wilson, PhD, University of Ghana
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
September 1, 2017
Primary Completion (Anticipated)
December 1, 2017
Study Completion (Anticipated)
December 1, 2017
Study Registration Dates
First Submitted
August 16, 2017
First Submitted That Met QC Criteria
August 22, 2017
First Posted (Actual)
August 25, 2017
Study Record Updates
Last Update Posted (Actual)
November 17, 2017
Last Update Submitted That Met QC Criteria
November 15, 2017
Last Verified
November 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Disease Attributes
- Parasitic Diseases
- Secernentea Infections
- Nematode Infections
- Helminthiasis
- Strongylida Infections
- Infections
- Communicable Diseases
- 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
- STH-MBZ-PO-4 02-GHA
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
IPD Plan Description
The final results of this study will be published in a scientific journal and presented at scientific conferences.
Any publication, lecture, and manuscripts of the findings of this study by any individual involved with the study will be governed by the procedure outlined in the Clinical Trial Agreement.
Within any presentation or publication, confidentiality of individual subjects will be maintained, with identification by subject code number and initials, if applicable.
A summary of study conclusions will be shared with the local community.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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