Severe MalariaSEMA ReACTNCT06806956
Severe Malaria in Remote Areas- Closing the Evidence Gap
An observational study of Severe Malaria, run by Tropical Diseases Research Centre, Zambia at 2 sites in 2 countries.
Trial summary
The goal of this observational study is to assess whether the giving of rectal artesunate and a three day course of an Artemisinin based Combination Therapy (ACT) to children aged 6 months and ≤ 5 years with severe malaria when referral is not feasible is non inferior to giving of injectable artesunate and three day… Read more about this study
- Who is it for?
- Ages 6 months to 5 years
- Conditions the study is for
- Severe Malaria
- What is being tested?
- Treatment of severe malaria with either RAS + ACT or RAS + injectable artesunate + ACT will each achieve the clinically acceptable cure rate of 97% ± 5% in remote areas
- Type of treatment
- Injection or infusion
- How many people
- 2,016 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 10 Mar 2024to Apr 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 months to 5 years
- All sexes
- No healthy volunteers
- Child
Study population: The study population will comprise children 6 months to ≤5 years of age living in Kapolowe, DRC and those living in Nchelenge, Zambia who present with a suspected diagnosis of severe malaria or uncomplicated malaria, confirmed by a rapid diagnostic test; or non-malaria severe disease
Who may be able to join
- From a village without other research interventions
- Children aged from 6 months to ≤5 years that present at the health system and are either; with fever (or history of fever within 2 days) and have a positive mRDT test plus at least one of the following danger signs for malaria (as per standardized national iCCM guidelines):
- convulsions
- inability to drink, eat, or suck
- vomiting all liquids and solids
- altered consciousness/coma
Show all 18Show fewer
- lethargy
- chest in-drawing Inclusion for uncomplicated malaria
- Children aged from 6 months to ≤5 years; with fever (or history of fever within 2 days) with no danger signs for malaria (as per the standardized national Integrated Management of Childhood Illnesses guidelines) with a positive mRDT for Plasmodium falciparum histidine-rich protein.
- From a village without other research interventions
- Children aged from 6 months to ≤5 years that present at the health system and are either; with fever (or history of fever within 2 days) and have a negative mRDT test plus at least one of the following danger signs as per standardized national iCCM guidelines:
- convulsions
- inability to drink, eat, or suck
- vomiting all liquids and solids
- altered consciousness/coma
- lethargy
- chest in-drawing
- For participants in sentinel sites, a written informed consent will be provided by the patient's parent or guardian to take filter paper blood samples and to participate in interviews (questionnaires and IDI) at enrolment, day 14 and day 28 (to assess malaria recurrence and look for markers of resistance). If the parent or guardian is unable to write, thumb print witnessed consent is permitted. The informed consent shall be administered by the CHWs. Willingness and ability of the patient and the parent or guardian to comply with the treatment policy.
Who cannot join
- Use of any investigational or non-registered product or planned use during the study period.
- Participation in other studies within 30 days before the current study begins and/or during study participation.
- Inability to comprehend and/or unwillingness to follow the study protocol.
- For RAS use: if the child has reacted badly to artesunate in the past (in sites where RAS is administered)
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Democratic Republic of the Congo1 site
University of Kinshasa
Kinshasa, Kinshasa City
About this study
Official title: Severe Malaria Treatment With Rectal Artesunate and Artemisinin-based Combination Therapy in Remote Settings
The goal of this observational study is to assess whether the giving of rectal artesunate and a three day course of an Artemisinin based Combination Therapy (ACT) to children aged 6 months and ≤ 5 years with severe malaria when referral is not feasible is non inferior to giving of injectable artesunate and three day course of an ACT. The three primary objectives are:
- To evaluate the 28-day PCR corrected cure rate in children aged 6 months to ≤ 5 years treated with RAS+ACT or RAS+injectable artesunate, assessing whether each treatment achieves the clinically acceptable cure rate of 97% ± 5%.
- To evaluate feasibility of provision of rapid treatment of severe malaria with rectal artesunate in children 6 months to ≤ 5 years not able to access a referral health facility, by a community health worker or in health facility where there is no injectable artesunate available.
- To evaluate the impact of reinforcing the integrated Community Case Management (iCCM) on access to the formal health care system
The study is being done in Nchelenge district in Zambia and Kapolowe district in the Democratic Republic of Congo. It will enrol 1008 children with severe malaria and an equal number of children with simple malaria
- Conditions
- Severe Malaria
- Being tested
- Treatment of severe malaria with either RAS + ACT or RAS + injectable artesunate + ACT will each achieve the clinically acceptable cure rate of 97% ± 5% in remote areas
- Keywords
- Rectal artesunate, Artemisinin-based Combination Therapy, Injectable artesunate, Community Health Worker, Health Facility
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment of severe malaria with either RAS + ACT or RAS + injectable artesunate + ACT will each achieve the clinically acceptable cure rate of 97% ± 5% in remote areasDrug
The Community Health Worker will give rectal artesunate (RAS) +artemisinin based combination Therapy (ACT) to children aged 6 months to less than or equal to 5 years who fail to make the referral trip. Those who make the referral trip will receive injectable artesunate and artemisinin based Combination Therapy for three days. Giving of RAS +ACT is unique to this study. Children with non malaria severe disease will also receive amoxicillin from the community health worker before they are referred to the next level of care
| Study group | Role | What they receive |
|---|---|---|
| Two groups i.e rectal artesunate +ACT group while the other is injectable artesunate +ACT group | The group of interest is children aged between 6 months and less than or equal to 5 years with severe malaria. However, we will also enrol children of the same age group with simple malaria and non malaria severe disease to compare their journeys as well Receives: Drug: Treatment of severe malaria with either RAS + ACT or RAS + injectable artesunate + ACT will each achieve the clinically acceptable cure rate of 97% ± 5% in remote areas |
What is being measured
The primary outcome is the main question the study is designed to answer.
The time from onset of symptoms to initiating treatment
The time from onset of symptoms to initiating treatment among children 6 months to ≤5 years with severe malaria and/or not able to take oral treatment that seek health care from the CHW or other HF system as primary first contact
Measured: The time from onset of symptoms to initiating treatment
PCR-corrected cure rate at 28 days from enrollment in patients aged 6 months to ≤5 years.
PCR-corrected cure rate at 28 Days from enrollment in patients aged 6 months to ≤5 years in areas where referral for follow-up treatment with injectable artesunate is not feasible, compared to outcomes obtained after full referral is completed
Measured: 28 Days from enrollment
Change from baseline proportion of sick children 6 months - ≤5 years at population level that went to the formal health system during the last 6 months including suspected (severe) malaria at month 20 (phase 4).
Two cross section surveys one at month 1 (baseline) and the other at month 20 (phase 4) will be used to obtain the proportion of sick children 6 months to ≤5 years at population level that were either attended by a Community Health Worker, Health post or Health Centre in the last 6 months
Measured: At month 20 (phase 4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2025
- Study start10 Mar 2024
- Primary completionMar 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe MalariaStudies 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 2,016 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tropical Diseases Research Centre, Zambia
- Sponsor type
- Other government
- Collaborators
- Universiteit Antwerpen, University of Kinshasa, National Institute for Medical Research, Tanzania, Medicines for Malaria Venture, Université de Lubumbashi
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06806956
- Sponsor's protocol ID
- Version 2.0 Dated 5 March 2024
- Other IDs
- 101103191
- Acronym
- SEMA ReACT
- Status last verified
- Jan 2026
- First submitted
- 29 Nov 2024
- Last updated
- 27 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We will only share aggregated data as IPD will not be useful to the research community
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Severe Malaria Treatment With Rectal Artesunate and Artemisinin-based Combination Therapy in Remote Settings
- ClinicalTrials.gov ID
- NCT06806956
- Acronym / sponsor ID
- SEMA ReACT / Version 2.0 Dated 5 March 2024
- Conditions
- Severe Malaria
- Keywords
- Rectal artesunate, Artemisinin-based Combination Therapy, Injectable artesunate, Community Health Worker, Health Facility
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 2,016 participants (estimated)
- Lead sponsor
- Tropical Diseases Research Centre, ZambiaOther government
- Collaborators
- Universiteit Antwerpen, University of Kinshasa, National Institute for Medical Research, Tanzania, Medicines for Malaria Venture, Université de Lubumbashi
- Study start
- 10 Mar 2024 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 4 Feb 2025 (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 goal of this observational study is to assess whether the giving of rectal artesunate and a three day course of an Artemisinin based Combination Therapy (ACT) to children aged 6 months and ≤ 5 years with severe malaria when referral is not feasible is non inferior to giving of injectable artesunate and three day course of an ACT. The three primary objectives are:
- To evaluate the 28-day PCR corrected cure rate in children aged 6 months to ≤ 5 years treated with RAS+ACT or RAS+injectable artesunate, assessing whether each treatment achieves the clinically acceptable cure rate of 97% ± 5%.
- To evaluate feasibility of provision of rapid treatment of severe malaria with rectal artesunate in children 6 months to ≤ 5 years not able to access a referral health facility, by a community health worker or in health facility where there is no injectable artesunate available.
- To evaluate the impact of reinforcing the integrated Community Case Management (iCCM) on access to the formal health care system
The study is being done in Nchelenge district in Zambia and Kapolowe district in the Democratic Republic of Congo. It will enrol 1008 children with severe malaria and an equal number of children with simple malaria
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Two groups i.e rectal artesunate +ACT group while the other is injectable artesunate +ACT group | – | Drug: Treatment of severe malaria with either RAS + ACT or RAS + injectable artesunate + ACT will each achieve the clinically acceptable cure rate of 97% ± 5% in remote areasThe group of interest is children aged between 6 months and less than or equal to 5 years with severe malaria. However, we will also enrol children of the same age group with simple malaria and non malaria severe disease to compare their journeys as well |
Who may qualify
- Ages
- 6 months to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- The study population will comprise children 6 months to ≤5 years of age living in Kapolowe, DRC and those living in Nchelenge, Zambia who present with a suspected diagnosis of severe malaria or uncomplicated malaria, confirmed by a rapid diagnostic test; or non-malaria severe disease
Key inclusion criteria (18 listed)
- From a village without other research interventions
- Children aged from 6 months to ≤5 years that present at the health system and are either; with fever (or history of fever within 2 days) and have a positive mRDT test plus at least one of the following danger signs for malaria (as per standardized national iCCM guidelines):
- Children aged from 6 months to ≤5 years; with fever (or history of fever within 2 days) with no danger signs for malaria (as per the standardized national Integrated Management of Childhood Illnesses guidelines) with a positive mRDT for Plasmodium falciparum histidine-rich protein.
- From a village without other research interventions
- Children aged from 6 months to ≤5 years that present at the health system and are either; with fever (or history of fever within 2 days) and have a negative mRDT test plus at least one of the following danger signs as per standardized national iCCM guidelines:
Key exclusion criteria (4 listed)
- Use of any investigational or non-registered product or planned use during the study period.
- Participation in other studies within 30 days before the current study begins and/or during study participation.
- Inability to comprehend and/or unwillingness to follow the study protocol.
- For RAS use: if the child has reacted badly to artesunate in the past (in sites where RAS is administered)
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 |
|---|---|---|
| Treatment of severe malaria with either RAS + ACT or RAS + injectable artesunate + ACT will each achieve the clinically acceptable cure rate of 97% ± 5% in remote areasThe Community Health Worker will give rectal artesunate (RAS) +artemisinin based combination Therapy (ACT) to children aged 6 months to less than or equal to 5 years who fail to make the referral trip. Those who make the referral trip will receive injectable artesunate and artemisinin based Combination Therapy for three days. Giving of RAS +ACT is unique to this study. Children with non malaria severe disease will also receive amoxicillin from the community health worker before they are referred to the next level of care | Drug | Two groups i.e rectal artesunate +ACT group while the other is injectable artesunate +ACT group |
Primary outcome
The time from onset of symptoms to initiating treatment
Time frame: The time from onset of symptoms to initiating treatment
The time from onset of symptoms to initiating treatment among children 6 months to ≤5 years with severe malaria and/or not able to take oral treatment that seek health care from the CHW or other HF system as primary first contact
PCR-corrected cure rate at 28 days from enrollment in patients aged 6 months to ≤5 years.
Time frame: 28 Days from enrollment
PCR-corrected cure rate at 28 Days from enrollment in patients aged 6 months to ≤5 years in areas where referral for follow-up treatment with injectable artesunate is not feasible, compared to outcomes obtained after full referral is completed
Change from baseline proportion of sick children 6 months - ≤5 years at population level that went to the formal health system during the last 6 months including suspected (severe) malaria at month 20 (phase 4).
Time frame: At month 20 (phase 4)
Two cross section surveys one at month 1 (baseline) and the other at month 20 (phase 4) will be used to obtain the proportion of sick children 6 months to ≤5 years at population level that were either attended by a Community Health Worker, Health post or Health Centre in the last 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- Individual participant dataSharing planned: No. We will only share aggregated data as IPD will not be useful to the research community
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Severe Malaria, run by Tropical Diseases Research Centre, Zambia at 2 sites in 2 countries.
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 18 inclusion and 4 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: enrolling by invitation, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Democratic Republic of the Congo, Zambia. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
The time from onset of symptoms to initiating treatment (time frame: The time from onset of symptoms to initiating treatment). 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?
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 27 Jan 2026.