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NCT Number: NCT03893097

Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children

The SchistoSAM study is an open label, two-arm, individually-randomized controlled trial with a non-inferiority design, conducted in northern Senegal.

The study aims at determining if the efficacy of one and of repeated courses of artesunate-mefloquine (AM) is respectively similar to or higher than that of a standard praziquantel (PZQ) treatment. Secondly, the study will assess if novel DNA- and antigen-based diagnostics are more accurate than microscopy in assessing antischistosomal treatment response.

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Key information

Conditions

Schistosoma Haematobium Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Helminthiasis Infections Male Urogenital Diseases Parasitic Diseases Schistosoma Mansoni Schistosomiasis Schistosomiasis haematobia Trematode Infections Urinary Tract Infections Urogenital Diseases Urologic Diseases Vector Borne Diseases

Age range

6 year–14 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formation (IRESSEF)

Dakar, Senegal

About this study

The SchistoSAM study is an open label, two-arm, individually-randomized controlled trial with a non-inferiority design, conducted in northern Senegal.

The study aims at determining if the efficacy of one and of repeated courses of artesunate-mefloquine (AM) is respectively similar to or higher than that of a standard praziquantel (PZQ) treatment. Secondly, the study will assess if novel DNA- and antigen-based diagnostics are more accurate than microscopy in assessing antischistosomal treatment response.

For this purpose, 726 school children, aged 6-14 years old and infected with Schistosoma (as demonstrated by presence of eggs in stool and/or urine) will be randomized in one of the following arms:

  • AM, available in fixed dose tablets of 25/50 mg and 100/200 mg will be administered once daily for three days in a dose closest to 4 mg/kg artesunate and 8 mg/kg mefloquine. This treatment course will be repeated 2 times at 6-week intervals.
  • PZQ, available in tablets of 600 mg, will be administered as a single dose of 40 mg/kg.

Trial participants will be regularly followed-up:

  • At each dose administration
  • At day 7 after each dose for follow-up of safety
  • At week 4, 10 and 16 for parasitological assessment and follow-up of safety
  • At week 6 and 12 for clinical assessment before the second and third drug administration (only in the AM arm)
  • At week 24 and 48 for assessment of Schistosoma spp. and malaria infection and associated morbidity (compared to baseline)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Children ≥6 and ≤14 years of age
  • Enrolled in one of the selected primary schools in the region
  • Infected with schistosomiasis (i.e. Schistosoma spp. eggs in urine and/or stool)
  • Informed consent from parents/guardians signed

Exclusion criteria

  • History of, or ongoing, epilepsy or psychiatric illness (I.e. recent history of depression, generalized anxiety disorder; history of psychosis, schizophrenia or other major psychiatric disorders) or known hypersensitivity to one of the three study drugs
  • Chronic medication for any reason
  • Any severe underlying illness, including severe malnutrition or severe chronic schistosomiasis, based on clinical judgement
  • Any febrile illness
  • Exposure to PZQ or ACT within the three previous months.

Treatment and study plan

Praziquantel

Drug

40 mg/kg at baseline

Artesunate + Mefloquine

Drug

4mg/kg artesunate and 8 mg/kg mefloquine at baseline (3 consecutive days) and repeated at Week 6 and Week 12

Primary outcomes

  1. Evaluate the efficacy of a single course of artesunate-mefloquine for the treatment of schistosomiasis, compared to the standard PZQ regimen: Parasitological cure rate

    Time frame: Week 4

    Parasitological cure rate, as assessed by microscopy, after administration of PZQ and after one AM course

  2. Number of safety events of a single course of artesunate-mefloquine for the treatment of schistosomiasis, compared to the standard PZQ regimen

    Time frame: Week 4

    Frequency of drug-related adverse events and serious adverse events

  3. Number of safety events of a single course of artesunate-mefloquine for the treatment of schistosomiasis, compared to the standard PZQ regimen

    Time frame: Week 4

    Pattern of drug-related adverse events and serious adverse events

Secondary outcomes

  1. Evaluate the cumulative efficacy of two additional courses of AM (at 6-week intervals each) for the treatment of schistosomiasis, compared to a single course of AM, and compared to the standard regimen: Cure rate

    Time frame: Week 48

    Cure rate, as assessed by microscopy, after the second and after the third AM administration

  2. Number of safety events of two additional courses of AM (at 6-week intervals each) for the treatment of schistosomiasis, compared to a single course of AM, and compared to the standard regimen.

    Time frame: Week 16

    Frequency of adverse events and serious adverse events up to 4 weeks after the second and third AM administration.

  3. Determine the egg reduction rate obtained after single and repeated courses of AM compared to the standard PZQ regimen.

    Time frame: Week 48

    Egg reduction rate after administration of PZQ and after each AM course

  4. Determine the parasitological efficacy of single and repeated courses of AM by Schistosoma species and by infection intensity.

    Time frame: Week 16

    Cure rate and egg reduction rate by Schistosoma species (S. haematobium and S. mansoni) and by initial Schistosoma infection intensity after PZQ administration and single and repeated courses of AM

  5. Assess the impact of repeated AM courses on schistosomiasis-related morbidity

    Time frame: Week 48

    Prevalence and severity of general and organ-specific schistosomiasis morbidity (as assessed by clinical evaluation, ultrasound, point-of-care morbidity markers and hemoglobin level) compared to baseline and compared to the control arm.

  6. Determine the diagnostic accuracy of novel schistosomiasis antigen- and DNA-based diagnostic assays to monitor antischistosomal treatment response

    Time frame: Week 48

    Diagnostic accuracy of the different conventional and novel diagnostic tests (antigen- and DNA-based) at baseline and at defined time points after treatment compared to conventional stool/urine microscopy, and to composite reference standards (any positive test would be considered as infection).

  7. Determine the effect of repeated AM courses on prevalence of P. falciparum infection as well as on incidence and morbidity of clinical malaria in school-age children with schistosomiasis

    Time frame: Week 48

    • Prevalence of malaria infection, as assessed by molecular testing of dried blood spots.
    • Incidence of clinical malaria, as assessed by the number of incident malaria cases diagnosed through passive case detection during the study period (by standard malaria rapid tests and molecular diagnostics on dried blood spots).
    • Frequency and severity of anemia, as assessed by determination of hemoglobin levels.

  8. Monitor the prevalence of Pf molecular markers associated with mefloquine resistance and the potential emergence of reduced artesunate susceptibility

    Time frame: Week 48

    Prevalence and patterns of mutations in the K13 gene (for artemisinin susceptibility) and increased copy number of the Pfmdr1 gene or other relevant mutations (for mefloquine resistance) observed in the molecular surveys Presence and patterns of mutations observed in incident malaria cases.

  9. Number of safety events of two additional courses of AM (at 6-week intervals each) for the treatment of schistosomiasis, compared to a single course of AM, and compared to the standard regimen.

    Time frame: Week 16

    Pattern of adverse events and serious adverse events up to 4 weeks after the second and third AM administration.

Sponsors and collaborators

Lead sponsor

Institute of Tropical Medicine, Belgium

Other

Collaborators

  • Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formation (IRESSEF)

Registry information

Official study title

A Proof-of-concept Trial to Evaluate Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children

Acronym: SchistoSAM

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Mar 28, 2019
Registry last updated
Apr 5, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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