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

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ClinicalTrials.gov Identifier: NCT03893097
Recruitment Status : Recruiting
First Posted : March 28, 2019
Last Update Posted : May 11, 2020
Sponsor:
Collaborator:
Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formation (IRESSEF)
Information provided by (Responsible Party):
Institute of Tropical Medicine, Belgium

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Schistosoma Haematobium Schistosoma Mansoni Drug: Praziquantel Drug: Artesunate + Mefloquine Phase 3

Detailed Description:

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:

  1. 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.
  2. 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:

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 726 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Proof-of-concept Trial to Evaluate Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children
Actual Study Start Date : October 14, 2019
Estimated Primary Completion Date : October 31, 2020
Estimated Study Completion Date : November 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Praziquantel
Participants in this arm will receive one dose of PZQ at baseline at 40 mg/kg.
Drug: Praziquantel
40 mg/kg at baseline

Experimental: Artesunate-Mefloquine
Participants in this arm will receive the Artesunate-Mefloquine (fixed-drug)combination at 4 mg/kg artesunate and 8 mg/kg mefloquine at 3 consecutive days. This will be repeated twice; at week 6 and week 12.
Drug: Artesunate + Mefloquine
4mg/kg artesunate and 8 mg/kg mefloquine at baseline (3 consecutive days) and repeated at Week 6 and Week 12




Primary Outcome Measures :
  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 Outcome Measures :
  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.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 14 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. 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
  2. Chronic medication for any reason
  3. Any severe underlying illness, including severe malnutrition or severe chronic schistosomiasis, based on clinical judgement
  4. Any febrile illness
  5. Exposure to PZQ or ACT within the three previous months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03893097


Contacts
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Contact: Emmanuel Bottieau, MD, PhD +32(0)32476450 ebottieau@itg.be
Contact: Katja Polman, PhD +32(0)32476204 kpolman@itg.be

Locations
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Senegal
Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formation (IRESSEF) Recruiting
Dakar, Senegal
Contact: Moustapha Mbow, MD       moustapha.mbow@iressef.org   
Sponsors and Collaborators
Institute of Tropical Medicine, Belgium
Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formation (IRESSEF)
Investigators
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Principal Investigator: Moustapha Mbow, MD IRESSEF
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Responsible Party: Institute of Tropical Medicine, Belgium
ClinicalTrials.gov Identifier: NCT03893097    
Other Study ID Numbers: 1269/18
First Posted: March 28, 2019    Key Record Dates
Last Update Posted: May 11, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institute of Tropical Medicine, Belgium:
Schistosoma
Schistosomiasis
Senegal
Praziquantel
Artesunate
Mefloquine
Additional relevant MeSH terms:
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Schistosomiasis
Trematode Infections
Helminthiasis
Parasitic Diseases
Artesunate
Mefloquine
Praziquantel
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics