Severe MalariaPhase 21STEP-ASNCT05140278
Study to Compare Feasibility of 1-step Injectable Artesunate vs. Conventional 2-step Injectable Artesunate
A Phase 2 study testing Argesun 60mg (1 step parenteral artesunate) and Artesun 60mg (2-step parenteral artesunate) in people with Severe Malaria, run by University of Oxford at 1 site in Democratic Republic of the Congo.
Trial summary
The objectives of this study contains 3 parts: (1) a comparison of 1-step parenteral artesunate (AS) versus conventional 2-step parenteral artesunate in patients with severe malaria to assess the feasibility of administration, parasite and fever clearance times in two countries, (2) a quantification of convenience and… Read more about this study
- Who is it for?
- Ages 3 months to 16 years
- Conditions the study is for
- Severe Malaria
- What is being tested?
- Argesun 60mg (1 step parenteral artesunate) and Artesun 60mg (2-step parenteral artesunate)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteDemocratic Republic of the Congo
- Study dates
- 18 Jul 2022to 11 Aug 2023
- Phase
- Phase 2
- 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 3 months to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Part 1:
- Male and female children aged >3months and <16 years.
- Clinical diagnosis of severe P. falciparum malaria; or parasitological confirmed P. falciparum hyperparasitaemia >350,000/ uL.
- Positive malaria test result, by rapid diagnostic test RDT.
- Weight of 5 kg or greater.
- Written informed consent by the parent or guardian.
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- Part 2:
- Study staff and health staff
- Study staff who prepare and administer Artesunate injection to patients in the study or health staff who have not administer the Artesunate injection to patients in the study by themselves but are either aware of malaria treatment, Artesunate injection, or have observed the treat-ment provided to severe malaria patients.
- Written informed consent by the study staff and health staff
- Study staff for a short video-record
- Study staff who would like to participate in the video record of a procedure to show how 1-step and 2-step Artesunate injections are prepared and administered.
- Written informed consent by the study staff
- Policymakers and stakeholders
- Those who are working in the National Malaria Control Program (NMCP) or relevant organizations (WHO, INGOs/NGOs) within the country.
- Written informed consent by the potential participant
Who cannot join
- Part 1:
- Participation in other intervention studies
- Known allergy to artemisinin derivatives.
- Known history of parenteral treatment for severe malaria for the current episode of illness before admission. Treatment before admission with an oral antimalarial drug (used for the treatment of uncomplicated malaria) or a single dose of pre-referral rectal artesunate are not exclusion criteria.
- Part 2:
- Study staff and health staff; Policymakers and stakeholders; Study staff and health staff for a short video-record
- Unwilling to participate in the study
- Unable to communicate
Trial locations and contacts
1 site in 1 country.
Democratic Republic of the Congo1 site
KIMORU (KIMORU /ESP Research Center)
Kinshasa, 8502
About this study
Official title: Convenience and Cost-aspects of a New 1-step Reconstitution Injectable Artesunate Compared to Conventional 2-step Injectable Artesunate for the Treatment of Severe Falciparum Malaria: a Multi-centre Study
The objectives of this study contains 3 parts: (1) a comparison of 1-step parenteral artesunate (AS) versus conventional 2-step parenteral artesunate in patients with severe malaria to assess the feasibility of administration, parasite and fever clearance times in two countries, (2) a quantification of convenience and costs of the new 1-step artesunate parenteral formulation versus the conventional formulation in a randomised study, (3) A cost analysis of 1-step parenteral artesunate using data from Part 1 \& Part 2. This will assess health facility-level costs, and also health system costs to encompass all costs of a potential change from conventional to 1-step artesunate, including re-training, materials, and drug replacement.
The conventional formulation of injectable artesunate requires a 2-step reconstitution and dilution of the artesunate hemisuccinate powder. A new formulation of injectable artesunate has been developed by Fosun Pharma requiring a simpler 1-step reconstitution. Bioequivalence of the new formulation to the conventional formulation.
For part 1, a total number of participants of this study would be 200 participants, estimated 100 per site will be recruited. For part 2, a total number of 40 semi-structured interviews with study staff, health staff, policy makers, and stake holders; and survey/questionnaires with 150 health staff.
Read the detailed description
Study design:
Part 1
A comparison of 1-step parenteral artesunate vs. conventional 2-step parenteral artesunate in patients with severe malaria to assess the feasibility of administration, parasite and fever clearance times of 1-step parenteral artesunate to conventional artesunate in 2 countries. Patients with severe malaria will be enrolled and randomly allocated to treatment with conventional injectable artesunate or 1-step injectable artesunate. A physical examination will be performed daily and every six hours on indication. Vital signs rec-orded hourly for unstable patients, then 6 hourly for stabilised patients, and at each follow-up visit. A symptom questionnaire will be taken daily to help identify adverse events. Patients will be asked to come back for a follow-up visit at day 7, 14, 21 and 28. Patients will not be followed up longer. In case of unresolved important sequelae at day 28, the patient will be followed and treated longer in order to provide the appropriate clinical care.
A Time and Motion study will record the time to prepare the artesunate solution for injection and administer treatment, number of actions performed to prepare treatment, and consumables used. Clinical, parasitological, and laboratory assessments will be recorded while patients are admitted in hospital and then weekly up to day 28 to assess recovery and determine final status.
Part 2
A mixed method social science study that entails semi-structure interviews and survey with study staff (involved in part 1), health workers (who treat severe malaria) and policymakers and stakeholders (who are involved in devising national malaria policy and its implementation), to assess the acceptability, feasibility, pros and cons, costs, and logistics and training implications of 1-step artesunate vs conventional artesunate. For both sites, semi-structure interviews will be conducted with minimum of a total of 40 respondents consisting of study staff, health staff and policy makers and stakeholders. The ultimate sample for semi-structure interviews will be dependent on the data saturation. For survey/questionnaire, a maximum number of relevant participants (study staff and health care staff) will be attempted to be recruited from two sites. A minimum of 150 study staff and health care staff will be recruited in the survey.
Part 3
A cost analysis of 1-step parenteral artesunate using data from Part 1 \& Part 2. This will assess health facility-level costs, and also health system costs to encompass all costs of a potential change from conventional to 1-step artesunate, including re-training, materials, drug replacement.
In addition to time measurement, the observer will also record the resources used for the administration of artesunate. This will include the vials themselves, as well as other consumables required for the administration (syringes, needles, catheters, etc.).
Funder:
- Shanghai Fosun Pharmaceutical Industrial Development Co., Ltd
- Mahidol-Oxford Tropical Medicine Research Unit supported by the Wellcome Trust, UK (220211)
- Conditions
- Severe Malaria
- Being tested
- Argesun 60mg (1 step parenteral artesunate), Artesun 60mg (2-step parenteral artesunate)
- Keywords
- Parenteral artesunate
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Argesun 60mg (1 step parenteral artesunate)Drug
Each vial of powder contains 60mg artesunate. Each ampoule of 6 ml solvent contains: sodium bicarbonate 8.4mg/ml; arginine 20mg/ml.
Artesun 60mg (2-step parenteral artesunate)Drug
Each vial of powder contains 60 mg artesunate. Each ampoule of 1 ml solvent contains 50 mg sodium bicarbonate. Each ampoule of 5 ml diluent contains 45 mg sodium chloride.
| Study group | Role | What they receive |
|---|---|---|
| 1-step Artesunate parenteral arm | Experimental | Argesun (Artesunate 60 mg) Receives: Drug: Argesun 60mg (1 step parenteral artesunate) |
| 2-step Artesunate parenteral arm | Experimental | Artesun (Artesunate 60 mg) Receives: Drug: Artesun 60mg (2-step parenteral artesunate) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to administration of treatment comparing 1-step vs. conventional 2-step parenteral artesunate formulations
Time to administration of treatment comparing 1-step vs. conventional 2-step parenteral artesunate formulations (by time-and-motion methods).
Measured: 3 days
Costs of administration of 1-step vs. conventional 2-step parenteral artesunate formulations
Costs of administration of 1-step vs. conventional 2-step parenteral artesunate formulations at health facility, and at health system level.
Measured: 3 days
Secondary outcomes (3)
Implementation perspective assessment of 1-step formulation of parenteral artesunate
Implementation perspective assessment of 1-step formulation of parenteral artesunate by interview study staff, health staff, and policymakers and stakeholders
Measured: 45 minutes
Practicability assessment of 1-step formulation of parenteral artesunate
Practicability assessment of 1-step formulation of parenteral artesunate by interview study staff, health staff, and policymakers and stakeholders
Measured: 45 minutes
Satisfaction assessment of 1-step formulation of parenteral artesunate
Satisfaction assessment of 1-step formulation of parenteral artesunate by interview study staff, health staff, and policymakers and stakeholders
Measured: 45 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2021
- Study start18 Jul 2022
- Primary completion29 Jul 2022
- Study completion11 Aug 2023
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.
- More trials run by University of OxfordThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd., University of Kinshasa, National Institute for Medical Research, Tanzania
- Responsible party
- Sponsor
- Investigators
- Caterina Fanello, Ph D, Principal investigator, Kinshasa School of Public HealthSamwell Gesase, MD, Principal investigator, Magunga District HospitalArjen Dondrop, MD, Principal investigator, Mahidol Oxford Tropical Medicine Research Unit Bangkok, ThailandMarie Akatshi Onyamboko, Principal investigator, Kinshasa School of Public Health, University of Kinshasa, DRC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05140278
- Sponsor's protocol ID
- MAL21006
- Acronym
- 1STEP-AS
- Status last verified
- Oct 2023
- First submitted
- 17 Nov 2021
- Last updated
- 15 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Participant's data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with data repositories or other researchers to use in the future. All personal information will be de-identified so that no individual can be identified from their treatment records, through interviews.
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Convenience and Cost-aspects of a New 1-step Reconstitution Injectable Artesunate Compared to Conventional 2-step Injectable Artesunate for the Treatment of Severe Falciparum Malaria: a Multi-centre Study
- ClinicalTrials.gov ID
- NCT05140278
- Acronym / sponsor ID
- 1STEP-AS / MAL21006
- Conditions
- Severe Malaria
- Keywords
- Parenteral artesunate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd., University of Kinshasa, National Institute for Medical Research, Tanzania
- Study start
- 18 Jul 2022 (actual)
- Primary completion
- 29 Jul 2022 (actual)
- Study completion
- 11 Aug 2023 (actual)
- First posted
- 1 Dec 2021 (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 objectives of this study contains 3 parts: (1) a comparison of 1-step parenteral artesunate (AS) versus conventional 2-step parenteral artesunate in patients with severe malaria to assess the feasibility of administration, parasite and fever clearance times in two countries, (2) a quantification of convenience and costs of the new 1-step artesunate parenteral formulation versus the conventional formulation in a randomised study, (3) A cost analysis of 1-step parenteral artesunate using data from Part 1 \& Part 2. This will assess health facility-level costs, and also health system costs to encompass all costs of a potential change from conventional to 1-step artesunate, including re-training, materials, and drug replacement.
The conventional formulation of injectable artesunate requires a 2-step reconstitution and dilution of the artesunate hemisuccinate powder. A new formulation of injectable artesunate has been developed by Fosun Pharma requiring a simpler 1-step reconstitution. Bioequivalence of the new formulation to the conventional formulation.
For part 1, a total number of participants of this study would be 200 participants, estimated 100 per site will be recruited. For part 2, a total number of 40 semi-structured interviews with study staff, health staff, policy makers, and stake holders; and survey/questionnaires with 150 health staff.
Detailed description
Study design:
Part 1
A comparison of 1-step parenteral artesunate vs. conventional 2-step parenteral artesunate in patients with severe malaria to assess the feasibility of administration, parasite and fever clearance times of 1-step parenteral artesunate to conventional artesunate in 2 countries. Patients with severe malaria will be enrolled and randomly allocated to treatment with conventional injectable artesunate or 1-step injectable artesunate. A physical examination will be performed daily and every six hours on indication. Vital signs rec-orded hourly for unstable patients, then 6 hourly for stabilised patients, and at each follow-up visit. A symptom questionnaire will be taken daily to help identify adverse events. Patients will be asked to come back for a follow-up visit at day 7, 14, 21 and 28. Patients will not be followed up longer. In case of unresolved important sequelae at day 28, the patient will be followed and treated longer in order to provide the appropriate clinical care.
A Time and Motion study will record the time to prepare the artesunate solution for injection and administer treatment, number of actions performed to prepare treatment, and consumables used. Clinical, parasitological, and laboratory assessments will be recorded while patients are admitted in hospital and then weekly up to day 28 to assess recovery and determine final status.
Part 2
A mixed method social science study that entails semi-structure interviews and survey with study staff (involved in part 1), health workers (who treat severe malaria) and policymakers and stakeholders (who are involved in devising national malaria policy and its implementation), to assess the acceptability, feasibility, pros and cons, costs, and logistics and training implications of 1-step artesunate vs conventional artesunate. For both sites, semi-structure interviews will be conducted with minimum of a total of 40 respondents consisting of study staff, health staff and policy makers and stakeholders. The ultimate sample for semi-structure interviews will be dependent on the data saturation. For survey/questionnaire, a maximum number of relevant participants (study staff and health care staff) will be attempted to be recruited from two sites. A minimum of 150 study staff and health care staff will be recruited in the survey.
Part 3
A cost analysis of 1-step parenteral artesunate using data from Part 1 \& Part 2. This will assess health facility-level costs, and also health system costs to encompass all costs of a potential change from conventional to 1-step artesunate, including re-training, materials, drug replacement.
In addition to time measurement, the observer will also record the resources used for the administration of artesunate. This will include the vials themselves, as well as other consumables required for the administration (syringes, needles, catheters, etc.).
Funder:
- Shanghai Fosun Pharmaceutical Industrial Development Co., Ltd
- Mahidol-Oxford Tropical Medicine Research Unit supported by the Wellcome Trust, UK (220211)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1-step Artesunate parenteral arm | Experimental | Drug: Argesun 60mg (1 step parenteral artesunate)Argesun (Artesunate 60 mg) |
| 2-step Artesunate parenteral arm | Experimental | Drug: Artesun 60mg (2-step parenteral artesunate)Artesun (Artesunate 60 mg) |
Who may qualify
- Ages
- 3 months to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (16 listed)
- Male and female children aged >3months and <16 years.
- Clinical diagnosis of severe P. falciparum malaria; or parasitological confirmed P. falciparum hyperparasitaemia >350,000/ uL.
- Positive malaria test result, by rapid diagnostic test RDT.
- Weight of 5 kg or greater.
- Written informed consent by the parent or guardian.
Key exclusion criteria (8 listed)
- Participation in other intervention studies
- Known allergy to artemisinin derivatives.
- Known history of parenteral treatment for severe malaria for the current episode of illness before admission. Treatment before admission with an oral antimalarial drug (used for the treatment of uncomplicated malaria) or a single dose of pre-referral rectal artesunate are not exclusion criteria.
- Study staff and health staff; Policymakers and stakeholders; Study staff and health staff for a short video-record
- Unwilling to participate in the study
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 |
|---|---|---|
| Argesun 60mg (1 step parenteral artesunate)Each vial of powder contains 60mg artesunate. Each ampoule of 6 ml solvent contains: sodium bicarbonate 8.4mg/ml; arginine 20mg/ml. | Drug | 1-step Artesunate parenteral arm |
| Artesun 60mg (2-step parenteral artesunate)Each vial of powder contains 60 mg artesunate. Each ampoule of 1 ml solvent contains 50 mg sodium bicarbonate. Each ampoule of 5 ml diluent contains 45 mg sodium chloride. | Drug | 2-step Artesunate parenteral arm |
Primary outcome
Time to administration of treatment comparing 1-step vs. conventional 2-step parenteral artesunate formulations
Time frame: 3 days
Time to administration of treatment comparing 1-step vs. conventional 2-step parenteral artesunate formulations (by time-and-motion methods).
Costs of administration of 1-step vs. conventional 2-step parenteral artesunate formulations
Time frame: 3 days
Costs of administration of 1-step vs. conventional 2-step parenteral artesunate formulations at health facility, and at health system level.
3 secondary outcomes
Implementation perspective assessment of 1-step formulation of parenteral artesunate
Time frame: 45 minutes
Practicability assessment of 1-step formulation of parenteral artesunate
Time frame: 45 minutes
Satisfaction assessment of 1-step formulation of parenteral artesunate
Time frame: 45 minutes
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 15 Mar 2024.
- Individual participant dataSharing planned: Yes. Participant's data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with data repositories or other researchers to use in the future. All personal information will be de-identified so that no individual can be identified from their treatment records, through interviews.
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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. This study is not recruiting at the moment.
Caterina Fanello, Ph D principal investigator
Kinshasa School of Public Health
Samwell Gesase, MD principal investigator
Magunga District Hospital
Arjen Dondrop, MD principal investigator
Mahidol Oxford Tropical Medicine Research Unit Bangkok, Thailand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Argesun 60mg (1 step parenteral artesunate) and Artesun 60mg (2-step parenteral artesunate) in people with Severe Malaria, run by University of Oxford at 1 site in Democratic Republic of the Congo.
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 16 inclusion and 8 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 15 Mar 2024. 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 Democratic Republic of the Congo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Time to administration of treatment comparing 1-step vs. conventional 2-step parenteral artesunate formulations (time frame: 3 days). The study lists 2 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 15 Mar 2024.