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

Sponsor

Institute of Tropical Medicine, Belgium (Other)

Overall Status

Completed

CT.gov ID

NCT03893097

Collaborator

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

726

Enrollment

Location

Arms

16.7

Actual Duration (Months)

43.6

Patients Per Site Per Month

Study Details

Study Description

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.

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)

Study Design

Study Type:

Interventional

Actual 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 :

Oct 14, 2019

Actual Primary Completion Date :

Mar 4, 2021

Actual Study Completion Date :

Mar 4, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Evaluate the efficacy of a single course of artesunate-mefloquine for the treatment of schistosomiasis, compared to the standard PZQ regimen: Parasitological cure rate [Week 4]
Parasitological cure rate, as assessed by microscopy, after administration of PZQ and after one AM course
Number of safety events of a single course of artesunate-mefloquine for the treatment of schistosomiasis, compared to the standard PZQ regimen [Week 4]
Frequency of drug-related adverse events and serious adverse events
Number of safety events of a single course of artesunate-mefloquine for the treatment of schistosomiasis, compared to the standard PZQ regimen [Week 4]
Pattern of drug-related adverse events and serious adverse events

Secondary Outcome Measures

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 [Week 48]
Cure rate, as assessed by microscopy, after the second and after the third AM administration
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. [Week 16]
Frequency of adverse events and serious adverse events up to 4 weeks after the second and third AM administration.
Determine the egg reduction rate obtained after single and repeated courses of AM compared to the standard PZQ regimen. [Week 48]
Egg reduction rate after administration of PZQ and after each AM course
Determine the parasitological efficacy of single and repeated courses of AM by Schistosoma species and by infection intensity. [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
Assess the impact of repeated AM courses on schistosomiasis-related morbidity [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.
Determine the diagnostic accuracy of novel schistosomiasis antigen- and DNA-based diagnostic assays to monitor antischistosomal treatment response [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).
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 [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.
Monitor the prevalence of Pf molecular markers associated with mefloquine resistance and the potential emergence of reduced artesunate susceptibility [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.
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. [Week 16]
Pattern of adverse events and serious adverse events up to 4 weeks after the second and third AM administration.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 14 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.