Efficacy and Safety of a Multi-dose Regimen of Mebendazole Against Hookworm in Children
Condition: Hookworm
MeSH terms: Hookworm Infections
Intervention: Treatment with one of the two regimens of mebendazole
Intervention description: Once in the morning and once in the evening for 3 consecutive days
Intervention MeSH terms: Mebendazole; Piperazine; Piperazine citrate; DMP 777
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: 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.
Enrollment: 186.0
Sex: All
Minimum age: 6 Years
Maximum age: 12 Years
Healthy volunteers: No

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 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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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).

        Exclusion Criteria:

        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).