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

NCT03893097 | Completed Phase 3 DMC

• 1 other identifier: 1269/18
• Study Type: interventional
• Target: 726
• Locations: 1 country
• Sites: 1

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.

Conditions

Schistosoma Haematobium; Schistosoma Mansoni

Keywords

Schistosoma; Schistosomiasis; Senegal; Praziquantel; Artesunate; Mefloquine

Outcome Measures

Primary Outcomes (3)

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

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

  Week 4

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

  Frequency of drug-related adverse events and serious adverse events

  Week 4

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

  Pattern of drug-related adverse events and serious adverse events

  Week 4

Secondary Outcomes (9)

• 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

• 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

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

  Week 48

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

  Week 16

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

  Week 48

Study Arms (2)

Praziquantel

ACTIVE COMPARATOR

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

Drug: Praziquantel

Artesunate-Mefloquine

EXPERIMENTAL

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

Interventions

Praziquantel DRUG

40 mg/kg at baseline

Praziquantel

Artesunate + Mefloquine DRUG

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

Artesunate-Mefloquine

Eligibility Criteria

• Age: 6 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formation (IRESSEF): collaborator

Study Sites (1)

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

Dakar, Senegal

Location

Related Publications (2)

• 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.

  PMID: 38177851 DERIVED

• 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.

  PMID: 34168029 DERIVED

MeSH Terms

Conditions

Schistosomiasis haematobia; Schistosomiasis

Interventions

Praziquantel; Artesunate; Mefloquine

Condition Hierarchy (Ancestors)

Trematode Infections; Helminthiasis; Parasitic Diseases; Infections; Urinary Tract Infections; Vector Borne Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Quinolines

Study Officials

• Moustapha Mbow, MD

  IRESSEF

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: March 28, 2019
• Study Start: October 14, 2019
• Primary Completion: March 4, 2021
• Study Completion: March 4, 2021
• Last Updated: April 5, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: We anticipate to deposit the individual participant data into the IDDO repository as soon as possible after publication of both findings on treatment efficacy and diagnostic accuracy, but no later than within one year. No end date is established for availability and access to the submitted data.
• Access Criteria: For the first five years from submission of the data, decisions regarding data access for third parties will be taken by the authors in collaboration with the ITM Data Access Committee (DAC). After five years, all requests for access to the Data from third parties shall automatically be delegated to DAC of IDDO. The IDDO DAC will provide controlled access to third party researchers whose applications for Data held within the IDDO repository are approved by the DAC in accordance with specific Data Access Guidelines. All requests are reviewed for qualifications of the researchers, the design and objectives of the secondary research, analysis plan and publication plan, consistency with ITM data sharing policies, applicable laws and regulations, and required ethics approvals.

Locations

SE (1)