Schistosoma HaematobiumPhase 3SchistoSAMNCT03893097
Evaluation of Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children
A Phase 3 study testing Praziquantel and Artesunate + Mefloquine in people with Schistosoma Haematobium and Schistosoma Mansoni, run by Institute of Tropical Medicine, Belgium at 1 site in Senegal.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 to 14 years
- Conditions the study is for
- Schistosoma Haematobium, Schistosoma Mansoni
- What is being tested?
- Praziquantel and Artesunate + Mefloquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 726 participants
- Where
- 1 siteSenegal
- Study dates
- 14 Oct 2019to 4 Mar 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Senegal1 site
Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formation (IRESSEF)
Dakar
About this study
Official title: A Proof-of-concept Trial to Evaluate Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children
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.
Read the 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:
- 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)
- Conditions
- Schistosoma Haematobium, Schistosoma Mansoni
- Being tested
- Praziquantel, Artesunate + Mefloquine
- Keywords
- Schistosoma, Schistosomiasis, Senegal, Praziquantel, Artesunate, Mefloquine
- Medical subject headings
- Schistosomiasis haematobia, Schistosomiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PraziquantelDrug
40 mg/kg at baseline
Artesunate + MefloquineDrug
4mg/kg artesunate and 8 mg/kg mefloquine at baseline (3 consecutive days) and repeated at Week 6 and Week 12
| Study group | Role | What they receive |
|---|---|---|
| Praziquantel | Active comparator | Participants in this arm will receive one dose of PZQ at baseline at 40 mg/kg. Receives: 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. Receives: Drug: Artesunate + Mefloquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Cure rate, as assessed by microscopy, after the second and after the third AM administration
Measured: 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.
Frequency of adverse events and serious adverse events up to 4 weeks after the second and third AM administration.
Measured: Week 16
Determine the egg reduction rate obtained after single and repeated courses of AM compared to the standard PZQ regimen.
Egg reduction rate after administration of PZQ and after each AM course
Measured: Week 48
Determine the parasitological efficacy of single and repeated courses of AM by Schistosoma species and by infection intensity.
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
Measured: Week 16
Assess the impact of repeated AM courses on schistosomiasis-related morbidity
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.
Measured: Week 48
Determine the diagnostic accuracy of novel schistosomiasis antigen- and DNA-based diagnostic assays to monitor antischistosomal treatment response
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).
Measured: Week 48
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
- 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.
Measured: Week 48
Monitor the prevalence of Pf molecular markers associated with mefloquine resistance and the potential emergence of reduced artesunate susceptibility
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.
Measured: 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.
Pattern of adverse events and serious adverse events up to 4 weeks after the second and third AM administration.
Measured: Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2019
- Study start14 Oct 2019
- Primary completion4 Mar 2021
- Study completion4 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Schistosoma HaematobiumStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 726 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Tropical Medicine, Belgium
- Sponsor type
- University, hospital or other
- Collaborators
- Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formation (IRESSEF)
- Responsible party
- Sponsor
- Investigators
- Moustapha Mbow, MD, Principal investigator, IRESSEF
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03893097
- Sponsor's protocol ID
- 1269/18
- Acronym
- SchistoSAM
- Status last verified
- Apr 2021
- First submitted
- 25 Mar 2019
- Last updated
- 5 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The proposed research will include data from 726 subjects, infected with Schistosomiasis and treated according to protocol in one of two arms. The final dataset will include phenotypic data such as demographics and medical history, results of the different diagnostic tests under investigation, clinical signs and symptoms, echography findings on Schistosomiasis induced morbidity, results of indirect morbidity markers under investigation, presence or absence of Plasmodium falciparum (Pf) and of Pf molecular resistance markers. All the individual participant data and additional supporting information will be deposited, after deidentification, at the IDDO - Schistosomiasis/STHs Data Platform. This is a platform specifically for Schistosomiasis/STHs data and is part of the IDDO project, an international collaboration hosted by the University of Oxford. The repository has data access policies and procedures consistent with ITM data sharing policies.
Publications
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.
PubMed 38177851Roucher 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.
PubMed 34168029
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof-of-concept Trial to Evaluate Artesunate-mefloquine as a Novel Alternative Treatment for Schistosomiasis in African Children
- ClinicalTrials.gov ID
- NCT03893097
- Acronym / sponsor ID
- SchistoSAM / 1269/18
- Conditions
- Schistosoma Haematobium, Schistosoma Mansoni
- Keywords
- Schistosoma, Schistosomiasis, Senegal, Praziquantel, Artesunate, Mefloquine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 726 participants (actual)
- Lead sponsor
- Institute of Tropical Medicine, BelgiumUniversity, hospital or other
- Collaborators
- Institut de Recherche en Santé, de Surveillance Épidémiologique et de Formation (IRESSEF)
- Study start
- 14 Oct 2019 (actual)
- Primary completion
- 4 Mar 2021 (actual)
- Study completion
- 4 Mar 2021 (actual)
- First posted
- 28 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Praziquantel | Active comparator | Drug: PraziquantelParticipants in this arm will receive one dose of PZQ at baseline at 40 mg/kg. |
| Artesunate-Mefloquine | Experimental | Drug: Artesunate + MefloquineParticipants 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. |
Who may qualify
- Ages
- 6 to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Praziquantel40 mg/kg at baseline | Drug | Praziquantel |
| Artesunate + Mefloquine4mg/kg artesunate and 8 mg/kg mefloquine at baseline (3 consecutive days) and repeated at Week 6 and Week 12 | Drug | Artesunate-Mefloquine |
Primary outcome
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
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
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
9 secondary outcomes
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
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
Determine the egg reduction rate obtained after single and repeated courses of AM compared to the standard PZQ regimen.
Time frame: Week 48
Determine the parasitological efficacy of single and repeated courses of AM by Schistosoma species and by infection intensity.
Time frame: Week 16
Assess the impact of repeated AM courses on schistosomiasis-related morbidity
Time frame: Week 48
Determine the diagnostic accuracy of novel schistosomiasis antigen- and DNA-based diagnostic assays to monitor antischistosomal treatment response
Time frame: Week 48
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
Monitor the prevalence of Pf molecular markers associated with mefloquine resistance and the potential emergence of reduced artesunate susceptibility
Time frame: 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.
Time frame: Week 16
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2021.
- Derived from this study: PubMed 38177851Bottieau 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.
- Derived from this study: PubMed 34168029Roucher 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.
- Individual participant dataSharing planned: Yes. The proposed research will include data from 726 subjects, infected with Schistosomiasis and treated according to protocol in one of two arms. The final dataset will include phenotypic data such as demographics and medical history, results of the different diagnostic tests under investigation, clinical signs and symptoms, echography findings on Schistosomiasis induced morbidity, results of indirect morbidity markers under investigation, presence or absence of Plasmodium falciparum (Pf) and of Pf molecular resistance markers. All the individual participant data and additional supporting information will be deposited, after deidentification, at the IDDO - Schistosomiasis/STHs Data Platform. This is a platform specifically for Schistosomiasis/STHs data and is part of the IDDO project, an international collaboration hosted by the University of Oxford. The repository has data access policies and procedures consistent with ITM data sharing policies.
Related trials for Schistosoma Haematobium
Not yet recruitingObservational study
Nanobody-based Schistosomiasis Urine Test Kit Research
Schistosomiasis Haematobia
Not yet recruitingObservational study
Possible Diagnostic Protein Markers in Schistosoma Related Bladder Diseases.
Schistosoma Haematobium
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Moustapha Mbow, MD principal investigator
IRESSEF
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Praziquantel and Artesunate + Mefloquine in people with Schistosoma Haematobium and Schistosoma Mansoni, run by Institute of Tropical Medicine, Belgium at 1 site in Senegal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Senegal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Week 4). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03893097, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2021.