Clinical trial NCT03893097: Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children
Official title: A Proof-of-concept Trial to Evaluate Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schistosoma Haematobium
Schistosoma Mansoni
Keywords: Schistosoma
Schistosomiasis
Senegal
Praziquantel
Artesunate
Mefloquine
Lead sponsor: Institute of Tropical Medicine, Belgium
Sponsor class: OTHER
Collaborators: name: Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formation (IRESSEF)
First posted: 2019-03-28
Enrollment: 726
Sex: ALL
Minimum age (years): 6
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Eligibility 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.

Primary outcomes:
measure: Evaluate the efficacy of a single course of artesunate-mefloquine for the treatment of schistosomiasis, compared to the standard PZQ regimen: Parasitological cure rate
timeFrame: Week 4
measure: Number of safety events of a single course of artesunate-mefloquine for the treatment of schistosomiasis, compared to the standard PZQ regimen
timeFrame: Week 4
measure: Number of safety events of a single course of artesunate-mefloquine for the treatment of schistosomiasis, compared to the standard PZQ regimen
timeFrame: Week 4
Secondary outcomes:
measure: 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
timeFrame: Week 48
measure: 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.
timeFrame: Week 16
measure: Determine the egg reduction rate obtained after single and repeated courses of AM compared to the standard PZQ regimen.
timeFrame: Week 48
measure: Determine the parasitological efficacy of single and repeated courses of AM by Schistosoma species and by infection intensity.
timeFrame: Week 16
measure: Assess the impact of repeated AM courses on schistosomiasis-related morbidity
timeFrame: Week 48
measure: Determine the diagnostic accuracy of novel schistosomiasis antigen- and DNA-based diagnostic assays to monitor antischistosomal treatment response
timeFrame: Week 48
measure: 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
timeFrame: Week 48
measure: Monitor the prevalence of Pf molecular markers associated with mefloquine resistance and the potential emergence of reduced artesunate susceptibility
timeFrame: Week 48
measure: 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.
timeFrame: Week 16
Other outcomes:
Locations:
city: Dakar
country: Senegal
facility: Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formation (IRESSEF)
Study officials:
affiliation: IRESSEF
name: Moustapha Mbow, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roucher C, Brosius I, Mbow M, Faye BT, De Hondt A, Smekens B, Arango D, Burm C, Tsoumanis A, Paredis L, van Herrewege Y, Potters I, Cisse B, Mboup S, Polman K, Bottieau E. Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM): protocol of a proof-of-concept, open-label, two-arm, individually-randomised controlled trial. BMJ Open. 2021 Jun 24;11(6):e047147. doi: 10.1136/bmjopen-2020-047147.