MalariaPhase 4CHIMIO2NCT04778813
Evaluation of Three Artemisinin-based Combinations for the Treatment of Uncomplicated Malaria in Childreen in Burkina Faso (CHIMIO2)
A Phase 4 study testing Artemether-lumefantrine in people with Malaria and Burkina Faso, run by Centre national de recherche et de formation sur le paludisme at 1 site in Burkina Faso.
Trial summary
Bakground In Burkina Faso, since the adoption of this new malaria treatment policy in 2005, several studies evaluating the efficacy and tolerance of ACTs have been carried out by different research teams at different sites according to an irregular chronology and according to different methods. Read more about this study
- Who is it for?
- Ages 6 months to 12 years
- Conditions the study is for
- Malaria, Burkina Faso
- What is being tested?
- Artemether-lumefantrine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,050 participants
- Where
- 1 siteBurkina Faso
- Study dates
- 1 Jun 2021to 1 Jun 2022
- Phase
- Phase 4
- 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 months to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children of both sexes aged 6 months to 12 years inclusive;
- Microscopic confirmation of a monospecific infection by P. falciparum (Parasitaemia between 2000 - 200,000 / μl);
- Fever (uncorrected axillary or tympanic temperature ≥37.5 ° C or history of fever reported within the last 24 hours
- Hemoglobin level ≥ 5.0 g / dl
- Ability to take oral medication;
- Ability and willingness of parents to respect the protocol for the duration of the study and to respect the consultation schedule;
- Signature (or fingerprint (thumb) when parents / guardians are illiterate) of the consent form by the child's parents or guardians.
Who cannot join
- General danger signs in children under five (inability to drink or breastfeed, repeated vomiting (> 2 times in 24 hours), convulsions, unconsciousness, inability to sit or stand standing)
- Body weight less than 5 kg;
- Fever due to illnesses other than malaria (e.g. measles, acute lower respiratory infection, severe diarrheal illness with dehydration) or presence of other known chronic or serious underlying illnesses or any other condition (e.g. illness cardiac, renal or hepatic, HIV / AIDS) which in the judgment of the clinical investigator would place the subject at potential risk or interfere with the conduct of the study;
- Previous complete antimalarial treatment with an ACT within the last two weeks;
- History of hypersensitivity to any of the drugs tested
- Severe malnutrition (defined by a z score of weight for age less than -3 or other severe malnutrition sign).
- Known individual or family history of clinical disorders of prolongation of QT intervals or sudden death
- Previous participation in a malaria vaccine clinical trial
Trial locations and contacts
1 site in 1 country.
Burkina Faso1 site
Centre national de recherche et de formation sur le paludisme (CNRFP)
Ouagadougou, Kadiogo, 2208
About this study
Bakground In Burkina Faso, since the adoption of this new malaria treatment policy in 2005, several studies evaluating the efficacy and tolerance of ACTs have been carried out by different research teams at different sites according to an irregular chronology and according to different methods. Studies conducted in children 6 to 59 months with supervised use of ACTs indicate adequate clinical and parasitological response rates varying between 93% to 98% after correction to the PCR at day 28. With the introduction of seasonal malaria chemoprevention (SMC) by the Sulfadoxine-Pyriméthamime/amodiaquine combination in almost all health districts of Burkina Faso, ASAQ is no longer recommended for the treatment of uncomplicated malaria in the areas covered by this intervention. In 2017, DHA-PPQ was added to the national treatment guidelines as a first-line treatment option. The therapeutic efficacy study carried out in 2017-2018 by the CNRFP showed a PCR-corrected treatment failure rate of over 10% with the AL combination. However, molecular analyzes have not shown the presence of mutations at position 580 on the PfK-13 gene which is associated with resistance to artemisinin derivatives. The combination artesunate-pyronaridine (As-Pyr) was recently added to the WHO Prequalified Medicines List and Essential Medicines List. In 2019, it received regulatory marketing authorization to be used as a treatment for malaria in Burkina Faso. Burkina Faso (along with the Niangoloko and Bobo Dioulasso centers) was one of the countries where clinical trials p ar the As-Pyr association were led. This combination has been found to be effective and well tolerated in Burkina Faso. The combinations of AL and DHA-PPQ were observed to be well tolerated in previous efficacy studies. The combinations DHA-PPQ and As-Pyr could potentially replace AL as first-line treatment in Burkina Faso if the results of these planned therapeutic efficacy studies continue to show a high rate of failures with AL. The herein study aims to assess the efficacy and safety of AL, DHA-PPQ and As-Pyr in the treatment of uncomplicated malaria in children in three health districts in Burkina Faso, namely the health districts of Banfora, Nanoro and de Gourcy. This study will provide PNLP and the Ministry of Health with additional data and evidence on the safety and efficacy of these treatments against malaria in Burkina Faso.
Primary objective The primary objective is to assess the clinical and parasitological efficacy of AL, DHA-PPQ and AS-Pyr in the treatment of uncomplicated P. falciparum malaria in children aged 6 months to 12 years, corrected by PCR on day 28 (AL) or 42 (DHA-PPQ \& AS-Pyr).
Read more
Study settings The study will be conducted at the medical center (CMA of Niangoloko, the Clinical Research Unit of Nanoro (URCN) and the medical center with surgical antenna (CMA) of Gourcy.
Populations Febrile patients of both sexes aged between 6 months and 12 years with confirmed uncomplicated P. falciparum mono-infestation who wellcome for an outpatient visit to the health facilities.
Procedures It will be a multicenter, randomized, open-label, three-arm study involving three sites representing the three epidemiological facies of malaria in Burkina Faso. The three therapeutic combinations (AL, DHA-PPQ and As-Pyr) will be tested in different sites with different characteristics of transmission and resistance of malaria. Children with uncomplicated malaria who meet the criteria for inclusion in the study will be recruited and treated with the combination of AL or DHA-PPQ or As-Pyr. They will be monitored for 28 days for the AL group and 42 days for the DHA-PPQ and AS-Pyr arm. The follow-up will consist of scheduled control visits during which clinical examinations and laboratory tests will be carried out. A total of 1050 children will be enrolled in the study.
Main results
- The proportion of patients with early treatment failure, late clinical failure, late parasitological failure or adequate clinical and parasitological response.
- The frequency and nature of adverse events.
- The blood concentration of lumefantrine on day 7
- Conditions
- Malaria, Burkina Faso
- Being tested
- Artemether-lumefantrine
- Keywords
- Plasmodium falciparum, Treatment, ACT, Childreen
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether-lumefantrineDrug
Also called Dihydroartemisinin pyperaquin, Artesunate Pyronaridine
In each study site, children fulfilling the inclusion criteria will be assigned randomly to one of three treatment groups: AL, DHA-PPQ or As-Pyr group. Sealed envelopes each containing no more than 10 other small envelopes with randomization numbers and treatment will also be provided. These will be used over time, respecting the ascending order of the numbers to randomly distribute the eligible children after selection in each of the three treatment groups. The treatment to be administered will not be known until after the randomization process. The drugs will be administered based on weight according to the instructions from the drug manufacturer. AL will be administered with fatty food or milk according to the manufacturer's recommendations. All doses of the drug will be administered under the direct supervision of a qualified team member designated by the principal investigator.
| Study group | Role | What they receive |
|---|---|---|
| Artemether-lumefantrin (AL) | Experimental | The tablets will be given orally according to patients' age and under supervision of study team as follows:
* Day 0: H0 and H8
* Day 1: H24 and H36
* Day 2: H48 and H60 Receives: Drug: Artemether-lumefantrine |
| Dihydro-artemisinin-piperaquin (DHA-PPQ) | Experimental | The tablets will be given orally according to patients' age and under supervision of study team as follows. A single dose will be given on day 0, 1 and 2 Receives: Drug: Artemether-lumefantrine |
| Artesunate-Pyronaridin (As-Pyr) | Experimental | The tablets will be given orally according to patients' age and under supervision of study team as follows. A single dose will be given on day 0, 1 and 2 Receives: Drug: Artemether-lumefantrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early treatment failure
- danger signs or severe malaria on Day 1, 2, or 3 in the presence of parasitemia;
- parasite count on Day 2 higher than on Day 0, irrespective of axillary temperature;
- parasitemia on Day 3 with axillary temperature ≥37.5°C;
- parasite count on Day 3 ≥25% on Day 0
Measured: 3 days
Late clinical failure
- danger signs or severe malaria on any day between Day 4 and Day 28 in the presence of parasitemia, without previously meeting any of the criteria of early treatment failure;
- presence of parasitemia and axillary temperature ≥37.5°C (or history of fever) on any day between Day 4 and Day 28, without previously meeting any of the criteria of early treatment failure
Measured: 24 days
Late parasitological failure
Presence of parasitemia on any day between Day 7 and Day 28 and axillary temperature <37.5°C, without previously meeting any of the criteria of early treatment failure or late clinical failure.
Measured: 21 days
Day 28 Adequate clinical and parasitological response PCR corrected
Absence of parasitaemia by day 28 without previously meeting any of the criteria for ETF, LCF and LPF. The number of cases of total treatment failure (TTF) will be computed as ETF+LCF+LPF
Measured: 28 days
Secondary outcomes (2)
Adverse events frequency and type
Any unwanted sign/symptom occurred in patients after consentement signature
Measured: 28 days
Pharmacocinetic of Lumefantrin
Concentration of lumefantrin in blood at day 7 after IP administration
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2021
- Study start1 Jun 2021 (estimated)
- Primary completion31 Dec 2021 (estimated)
- Study completion1 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a multicenter, randomized, open-label, three-arm study involving three sites representing the three different epidemiological facies of malaria in Burkina Faso.The three therapeutic combinations (AL, DHA-PPQ and As-Pyr) will be tested in different sites with different characteristics of transmission and resistance of malaria. Participants will be treated for 3 days then followed during by 28-days (AL arm) and 42-days (DHA-PPQ and Pas-Pyr). There will be no comparision between study arms, but the for each arm, the efficacy will be measured and compared to WHO critical value.
- Masking
- None (open label)
- Enrolment
- 1,050 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre national de recherche et de formation sur le paludisme
- Sponsor type
- Other government
- Collaborators
- Programme National de Lutte contre le Paludisme, Niger, Unité de recherche clinique de Nanoro (URCN), USAID/IMPACT Malaria
- Responsible party
- Sponsor
- Investigators
- Adama Gansane, PhD, Principal investigator, Centre national de recherche et de formation sur le paludisme
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04778813
- Sponsor's protocol ID
- TET2020_001
- Acronym
- CHIMIO2
- Status last verified
- Feb 2021
- First submitted
- 24 Feb 2021
- Last updated
- 3 Mar 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Three Artemisinin-based Combinations for the Treatment of Uncomplicated Malaria in Childreen in Burkina Faso (CHIMIO2)
- ClinicalTrials.gov ID
- NCT04778813
- Acronym / sponsor ID
- CHIMIO2 / TET2020_001
- Conditions
- Malaria, Burkina Faso
- Keywords
- Plasmodium falciparum, Treatment, ACT, Childreen
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,050 participants (estimated)
- Lead sponsor
- Centre national de recherche et de formation sur le paludismeOther government
- Collaborators
- Programme National de Lutte contre le Paludisme, Niger, Unité de recherche clinique de Nanoro (URCN), USAID/IMPACT Malaria
- Study start
- 1 Jun 2021 (estimated)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 1 Jun 2022 (estimated)
- First posted
- 3 Mar 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.
Bakground In Burkina Faso, since the adoption of this new malaria treatment policy in 2005, several studies evaluating the efficacy and tolerance of ACTs have been carried out by different research teams at different sites according to an irregular chronology and according to different methods. Studies conducted in children 6 to 59 months with supervised use of ACTs indicate adequate clinical and parasitological response rates varying between 93% to 98% after correction to the PCR at day 28. With the introduction of seasonal malaria chemoprevention (SMC) by the Sulfadoxine-Pyriméthamime/amodiaquine combination in almost all health districts of Burkina Faso, ASAQ is no longer recommended for the treatment of uncomplicated malaria in the areas covered by this intervention. In 2017, DHA-PPQ was added to the national treatment guidelines as a first-line treatment option. The therapeutic efficacy study carried out in 2017-2018 by the CNRFP showed a PCR-corrected treatment failure rate of over 10% with the AL combination. However, molecular analyzes have not shown the presence of mutations at position 580 on the PfK-13 gene which is associated with resistance to artemisinin derivatives. The combination artesunate-pyronaridine (As-Pyr) was recently added to the WHO Prequalified Medicines List and Essential Medicines List. In 2019, it received regulatory marketing authorization to be used as a treatment for malaria in Burkina Faso. Burkina Faso (along with the Niangoloko and Bobo Dioulasso centers) was one of the countries where clinical trials p ar the As-Pyr association were led. This combination has been found to be effective and well tolerated in Burkina Faso. The combinations of AL and DHA-PPQ were observed to be well tolerated in previous efficacy studies. The combinations DHA-PPQ and As-Pyr could potentially replace AL as first-line treatment in Burkina Faso if the results of these planned therapeutic efficacy studies continue to show a high rate of failures with AL. The herein study aims to assess the efficacy and safety of AL, DHA-PPQ and As-Pyr in the treatment of uncomplicated malaria in children in three health districts in Burkina Faso, namely the health districts of Banfora, Nanoro and de Gourcy. This study will provide PNLP and the Ministry of Health with additional data and evidence on the safety and efficacy of these treatments against malaria in Burkina Faso.
Primary objective The primary objective is to assess the clinical and parasitological efficacy of AL, DHA-PPQ and AS-Pyr in the treatment of uncomplicated P. falciparum malaria in children aged 6 months to 12 years, corrected by PCR on day 28 (AL) or 42 (DHA-PPQ \& AS-Pyr).
Study settings The study will be conducted at the medical center (CMA of Niangoloko, the Clinical Research Unit of Nanoro (URCN) and the medical center with surgical antenna (CMA) of Gourcy.
Populations Febrile patients of both sexes aged between 6 months and 12 years with confirmed uncomplicated P. falciparum mono-infestation who wellcome for an outpatient visit to the health facilities.
Procedures It will be a multicenter, randomized, open-label, three-arm study involving three sites representing the three epidemiological facies of malaria in Burkina Faso. The three therapeutic combinations (AL, DHA-PPQ and As-Pyr) will be tested in different sites with different characteristics of transmission and resistance of malaria. Children with uncomplicated malaria who meet the criteria for inclusion in the study will be recruited and treated with the combination of AL or DHA-PPQ or As-Pyr. They will be monitored for 28 days for the AL group and 42 days for the DHA-PPQ and AS-Pyr arm. The follow-up will consist of scheduled control visits during which clinical examinations and laboratory tests will be carried out. A total of 1050 children will be enrolled in the study.
Main results
- The proportion of patients with early treatment failure, late clinical failure, late parasitological failure or adequate clinical and parasitological response.
- The frequency and nature of adverse events.
- The blood concentration of lumefantrine on day 7
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This is a multicenter, randomized, open-label, three-arm study involving three sites representing the three different epidemiological facies of malaria in Burkina Faso.The three therapeutic combinations (AL, DHA-PPQ and As-Pyr) will be tested in different sites with different characteristics of transmission and resistance of malaria. Participants will be treated for 3 days then followed during by 28-days (AL arm) and 42-days (DHA-PPQ and Pas-Pyr). There will be no comparision between study arms, but the for each arm, the efficacy will be measured and compared to WHO critical value.
| Arm | Type | Receives |
|---|---|---|
| Artemether-lumefantrin (AL) | Experimental | Drug: Artemether-lumefantrineThe tablets will be given orally according to patients' age and under supervision of study team as follows: * Day 0: H0 and H8 * Day 1: H24 and H36 * Day 2: H48 and H60 |
| Dihydro-artemisinin-piperaquin (DHA-PPQ) | Experimental | Drug: Artemether-lumefantrineThe tablets will be given orally according to patients' age and under supervision of study team as follows. A single dose will be given on day 0, 1 and 2 |
| Artesunate-Pyronaridin (As-Pyr) | Experimental | Drug: Artemether-lumefantrineThe tablets will be given orally according to patients' age and under supervision of study team as follows. A single dose will be given on day 0, 1 and 2 |
Who may qualify
- Ages
- 6 months to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Children of both sexes aged 6 months to 12 years inclusive;
- Microscopic confirmation of a monospecific infection by P. falciparum (Parasitaemia between 2000 - 200,000 / μl);
- Fever (uncorrected axillary or tympanic temperature ≥37.5 ° C or history of fever reported within the last 24 hours
- Hemoglobin level ≥ 5.0 g / dl
- Ability to take oral medication;
Key exclusion criteria (8 listed)
- General danger signs in children under five (inability to drink or breastfeed, repeated vomiting (> 2 times in 24 hours), convulsions, unconsciousness, inability to sit or stand standing)
- Body weight less than 5 kg;
- Fever due to illnesses other than malaria (e.g. measles, acute lower respiratory infection, severe diarrheal illness with dehydration) or presence of other known chronic or serious underlying illnesses or any other condition (e.g. illness cardiac, renal or hepatic, HIV / AIDS) which in the judgment of the clinical investigator would place the subject at potential risk or interfere with the conduct of the study;
- Previous complete antimalarial treatment with an ACT within the last two weeks;
- History of hypersensitivity to any of the drugs tested
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 |
|---|---|---|
| Artemether-lumefantrineAlso: Dihydroartemisinin pyperaquin, Artesunate PyronaridineIn each study site, children fulfilling the inclusion criteria will be assigned randomly to one of three treatment groups: AL, DHA-PPQ or As-Pyr group. Sealed envelopes each containing no more than 10 other small envelopes with randomization numbers and treatment will also be provided. These will be used over time, respecting the ascending order of the numbers to randomly distribute the eligible children after selection in each of the three treatment groups. The treatment to be administered will not be known until after the randomization process. The drugs will be administered based on weight according to the instructions from the drug manufacturer. AL will be administered with fatty food or milk according to the manufacturer's recommendations. All doses of the drug will be administered under the direct supervision of a qualified team member designated by the principal investigator. | Drug | Artemether-lumefantrin (AL), Artesunate-Pyronaridin (As-Pyr), Dihydro-artemisinin-piperaquin (DHA-PPQ) |
Primary outcome
Early treatment failure
Time frame: 3 days
* danger signs or severe malaria on Day 1, 2, or 3 in the presence of parasitemia; * parasite count on Day 2 higher than on Day 0, irrespective of axillary temperature; * parasitemia on Day 3 with axillary temperature ≥37.5°C; * parasite count on Day 3 ≥25% on Day 0
Late clinical failure
Time frame: 24 days
* danger signs or severe malaria on any day between Day 4 and Day 28 in the presence of parasitemia, without previously meeting any of the criteria of early treatment failure; * presence of parasitemia and axillary temperature ≥37.5°C (or history of fever) on any day between Day 4 and Day 28, without previously meeting any of the criteria of early treatment failure
Late parasitological failure
Time frame: 21 days
Presence of parasitemia on any day between Day 7 and Day 28 and axillary temperature <37.5°C, without previously meeting any of the criteria of early treatment failure or late clinical failure.
Day 28 Adequate clinical and parasitological response PCR corrected
Time frame: 28 days
Absence of parasitaemia by day 28 without previously meeting any of the criteria for ETF, LCF and LPF. The number of cases of total treatment failure (TTF) will be computed as ETF+LCF+LPF
2 secondary outcomes
Adverse events frequency and type
Time frame: 28 days
Pharmacocinetic of Lumefantrin
Time frame: 7 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2021.
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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.
Adama Gansane, PhD principal investigator
Centre national de recherche et de formation sur le paludisme
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Artemether-lumefantrine in people with Malaria and Burkina Faso, run by Centre national de recherche et de formation sur le paludisme at 1 site in Burkina Faso.
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 7 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: status not confirmed, as of the sponsor's last update on 3 Mar 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 Burkina Faso. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Adama Gansane, PharmD, PhD (+22670233723, agansane@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early treatment failure (time frame: 3 days). The study lists 4 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 3 Mar 2021.