Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| PATH | OTHER |
| Public Health Laboratory Ivo de Carneri | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Treatment with one of the two regimens of mebendazole | Drug | Once in the morning and once in the evening for 3 consecutive days |
|
| 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 18 to 22 days post-treatment |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of the Sensitivity of Kato Katz to Quantitative Polymerase Chain Reaction (PCR) Assays | Two aliquots (about 1 g of stool each) of positive samples will be stored in ethanol and transported to the Swiss Tropical Public Health Institute for subsequent DNA extraction and diagnostic. | 1 year |
| Prevalence of Genetic Resistance Markers Among Participants |
Inclusion Criteria:
Exclusion Criteria:
No written informed consent by parents and/or caregiver; no oral assent by participant.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jennifer Keiser, PhD | Swiss Tropical & Public Health Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Public Health Laboratory Ivo de Carneri, P.O. Box 122 | Chake Chake | Pemba | Tanzania |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31193620 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Single 500 mg Dose of Mebendazole | In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days |
| FG001 | Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole | In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Single 500 mg Dose of Mebendazole | In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | 95% Confidence Interval | percentage of participants cured | baseline (before treatment) and 18 to 22 days post-treatment |
|
Adverse event data collected 3h after the first treatment time point
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Single 500 mg Dose of Mebendazole | In the morning of day 1 each child in this treatment arm received a 500 mg tablet of mebendazole plus one 100 mg placebo tablet. In the afternoon of day 1 they only received the placebo. In day 2 and 3 each child received one placebo tablet twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Jennifer Keiser | Swiss Tropical and Public Health Institute | +41 61 284 8218 | jennifer.keiser@swisstph.ch |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jul 17, 2017 | Nov 20, 2018 | Prot_SAP_ICF_000.pdf |
Not provided
| ID | Term |
|---|---|
| D000724 | Ancylostomiasis |
| ID | Term |
|---|---|
| D006725 | Hookworm Infections |
| D017206 | Strongylida Infections |
| D017190 | Secernentea Infections |
| D009349 | Nematode Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D013812 | Therapeutics |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Participants, physicians, nurses and investigators will all be blinded. Based on the randomization list, individual envelopes with the correct combination of mebendazole tablets and placebos will be prepared. The randomization code is then sealed in an envelope. Unblinding will only occur in case of a SAE, SUSAR or other kind of emergency.
| 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. | 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). | 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. | 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). | 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). | 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). | 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). | baseline (before treatment) and 18 to 22 days post-treatment |
The same two aliquots of stool will be used in this section.. Additionally, a Harada Mori culture will be prepared from one of the stool samples of each child at baseline and at follow-up to extract hatched larvae. Larvae will be stored in ethanol. Both stool and larvae samples will undergo an assessment of drug resistance-associated single-nucleotide polymorphisms. |
| 2 years |
| Distribution of Hookworm Species Among Participants | Genetic differentiation between Necator americanus and Ancylostoma duodenale using PCRs will allow us to identify which of the species is most prevalent. | 1 year |
| BG001 | Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole | In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Mean weight (kg) | Mean | Standard Deviation | kg |
|
| Mean height (cm) | Mean | Standard Deviation | cm |
|
| Infected with hookworm | Count of Participants | Participants |
|
| Median EPG hookworm | Median | Inter-Quartile Range | Eggs per gram (EPG) |
|
| EPG hookworm (geometric mean) | Geometric Mean | Full Range | EPG |
|
| Light hookworm infection (1-1999 EPG) | Count of Participants | Participants |
|
| Moderate hookworm infection (2000-3999 EPG) | Count of Participants | Participants |
|
| Heavy hookworm infection (≥4000 EPG) | Count of Participants | Participants |
|
| Infected with T. trichiura | Count of Participants | Participants |
|
| EPG T. trichiura (geometric mean) | Geometric Mean | Full Range | EPG |
|
| Light T. trichiura infection (1-999 EPG) | Count of Participants | Participants |
|
| Moderate T. trichiura infection (1000-9999 EPG) | Count of Participants | Participants |
|
| Heavy T. trichiura infection (≥10,000 EPG) | Count of Participants | Participants |
|
| Infected with A. lumbricoides | Count of Participants | Participants |
|
| EPG A. lumbricoides (geometric mean) | Geometric Mean | Full Range | EPG |
|
| Light A. lumbricoides infection (1-4999 EPG) | Count of Participants | Participants |
|
| Moderate A. lumbricoides infection (5000-49,999 EPG) | Count of Participants | Participants |
|
| Heavy A. lumbricoides infection (≥50,000 EPG) | Count of Participants | Participants |
|
In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days |
|
|
| Secondary | 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). | Posted | Geometric Mean | 95% Confidence Interval | percentage change | baseline (before treatment) and 18 to 22 days post-treatment |
|
|
|
| Secondary | 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. | Posted | Number | 95% Confidence Interval | percentage of participants cured | baseline (before treatment) and 18 to 22 days post-treatment |
|
|
|
| Secondary | 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). | Posted | Mean | 95% Confidence Interval | percentage of change | baseline (before treatment) and 18 to 22 days post-treatment |
|
|
|
| Secondary | 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. | Posted | Number | 95% Confidence Interval | percentage of participants cured | baseline (before treatment) and 18 to 22 days post-treatment |
|
|
|
| Secondary | 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). | Posted | Mean | 95% Confidence Interval | percentage change | baseline (before treatment) and 18 to 22 days post-treatment |
|
|
|
| Secondary | 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). | Posted | Mean | 95% Confidence Interval | percentage change | baseline (before treatment) and 18 to 22 days post-treatment |
|
|
|
| Secondary | 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). | Posted | Mean | 95% Confidence Interval | percentage change | baseline (before treatment) and 18 to 22 days post-treatment |
|
|
|
| Secondary | 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). | Posted | Mean | 95% Confidence Interval | percentage change | baseline (before treatment) and 18 to 22 days post-treatment |
|
|
|
| Other Pre-specified | Comparison of the Sensitivity of Kato Katz to Quantitative Polymerase Chain Reaction (PCR) Assays | Two aliquots (about 1 g of stool each) of positive samples will be stored in ethanol and transported to the Swiss Tropical Public Health Institute for subsequent DNA extraction and diagnostic. | Not Posted | 1 year | Participants |
| Other Pre-specified | Prevalence of Genetic Resistance Markers Among Participants | The same two aliquots of stool will be used in this section.. Additionally, a Harada Mori culture will be prepared from one of the stool samples of each child at baseline and at follow-up to extract hatched larvae. Larvae will be stored in ethanol. Both stool and larvae samples will undergo an assessment of drug resistance-associated single-nucleotide polymorphisms. | Not Posted | 2 years | Participants |
| Other Pre-specified | Distribution of Hookworm Species Among Participants | Genetic differentiation between Necator americanus and Ancylostoma duodenale using PCRs will allow us to identify which of the species is most prevalent. | Not Posted | 1 year | Participants |
| 0 |
| 93 |
| 0 |
| 93 |
| 2 |
| 93 |
| EG001 | Multiple (Bid for 3 Days) Dose of 100 mg Mebendazole | In the morning of day 1 each child in this treatment arm received a 100 mg tablet of mebendazole plus one 500 mg placebo tablet. In the afternoon of day 1 they only received the 100 mg tablet of mebendazole. In day 2 and 3 each child received one 100 mg tablet of mebendazole twice a day (in the morning and in the evening). Treatment with one of the two regimens of mebendazole: Once in the morning and once in the evening for 3 consecutive days | 0 | 93 | 0 | 93 | 8 | 93 |
Not provided
Not provided
Not provided
| D006373 |
| Helminthiasis |
| D010272 | Parasitic Diseases |
| D007239 | Infections |