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

NCT ID: NCT03893097

Last Updated: 2021-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 726 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-14
• Study Completion Date: 2021-03-04

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)

Conditions

Schistosoma Haematobium; Schistosoma Mansoni

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Praziquantel

Participants in this arm will receive one dose of PZQ at baseline at 40 mg/kg.

Group Type: ACTIVE_COMPARATOR

Praziquantel

Intervention Type: DRUG

40 mg/kg at baseline

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.

Group Type: EXPERIMENTAL

Artesunate + Mefloquine

Intervention Type: DRUG

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

Interventions

Praziquantel

40 mg/kg at baseline

Intervention Type: DRUG

Artesunate + Mefloquine

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

UNKNOWN

Sponsor Role: collaborator

Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Moustapha Mbow, MD

Role: PRINCIPAL_INVESTIGATOR

IRESSEF

Locations

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

Dakar, , Senegal

Countries

Senegal

References

Bottieau E, Mbow M, Brosius I, Roucher C, Gueye CT, Mbodj OT, Faye BT, De Hondt A, Smekens B, Arango D, Burm C, Tsoumanis A, Paredis L, Van Herrewege Y, Potters I, Richter J, Rosanas-Urgell A, Cisse B, Mboup S, Polman K. Antimalarial artesunate-mefloquine versus praziquantel in African children with schistosomiasis: an open-label, randomized controlled trial. Nat Med. 2024 Jan;30(1):130-137. doi: 10.1038/s41591-023-02719-4. Epub 2024 Jan 4.

Reference Type: DERIVED

PMID: 38177851 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34168029 (View on PubMed)

Other Identifiers

1269/18

Identifier Type: -

Identifier Source: org_study_id