Mebendazole Study Against Hookworm Infections in Children and Adolescents in Ghana

Hookworm Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03261596
• Other study ID #: STH-MBZ-PO-4 02-GHA
• Status: Withdrawn
• Phase: Phase 4
• First received: August 16, 2017
• Last updated: November 15, 2017
• Start date: September 2017
• Est. completion date: December 2017

Study information

• Verified date: November 2017
• Source: PATH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

Inclusion Criteria

All participants must meet all of the following inclusion criteria:

1. Male or female, aged 6 to 18 years, inclusive, at the time of randomization.

2. Written informed consent signed by at least one parent and/or legally acceptable representative (as defined by local law); and assent by participant.

3. Able and willing to be examined by a study health care provider at the beginning of the study.

4. Able and willing to provide one stool sample at the beginning (baseline) and one sample approximately three weeks after treatment (follow-up).

5. 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:

1. Presence of major systemic illnesses as assessed by a study health care provider, upon initial targeted clinical assessment.

2. Pregnancy, based on a positive urine rapid test, or breastfeeding in girls after menarche.

3. Recent use of an anthelminthic drug (within the past 4 weeks) or use of anthelminthics not provided by study staff during the study period.

4. Known allergy to mebendazole or albendazole.

5. Participation in other clinical trials during the study.

Related Conditions & MeSH terms

• Communicable Diseases
• Hookworm Infections
• Infection

Intervention

Drug:
• Mebendazole
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.

Locations

Country	Name	City	State
Ghana	Noguchi Memorial Institute for Medical Research - University of Ghana	Legon	Accra

Sponsors (6)

Lead Sponsor	Collaborator
PATH	Ghana Health Services, HopeXchange Medical Center, Ghana, Kintampo Health Research Centre, Ghana, Noguchi Memorial Institute for Medical Research, Yale University

Country where clinical trial is conducted

Ghana, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sensitivity of Kato-Katz and PCR for hookworm infection detection	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.	Up to 14 weeks following Day 20
Other	Prevalence of hookworm genetic resistance markers	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.	Up to 14 weeks following Day 20
Other	Distribution of hookworm species among participants	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.	Up to 14 weeks following Day 20
Primary	Cure Rate (CR) against hookworm, as determined by Kato Katz.	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.	20 days
Secondary	Egg reduction rate (ERR), based on geometric mean, against hookworm	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.	20 days
Secondary	CR and ERR against Ascaris lumbricoides and Trichuris trichiura	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.	20 days
Secondary	Adverse Events	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%.	Through 20 days of follow-up