Uncomplicated Plasmodium Falciparum Malaria
Conditions
Keywords
Uncomplicated malaria, Plasmodium falciparum, Artemisinin-based Combination Treatment, Artemether-lumefantrine, Artesunate-amodiaquine
Brief summary
Malaria remains a public health concern, despite efforts that are invested in the disease control. The Democratic Republic of the Congo (DRC) is one of the most affected countries in Sub Saharan Africa. Artemisinin-based combination treatments (ACTs) are recommended for the treatment of uncomplicated malaria. However, reported cases of mutations that confer to Plasmodium falciparum resistance to artemisinin (the main component of ACTs) constitute a threat to malaria control, particularly in Sub Saharan Africa. Therefore, the recommendation of the World Health Organization to conduct regularly test efficacy studies in endemic countries is paramount. The purpose of this trial is to assess efficacy and safety of artesunate-amodiaquine (ASAQ Winthrop®) and artemether-lumefantrine (Coartem Dispersible®) at day 28 for the treatment of uncomplicated Plasmodium falciparum malaria in eight surveillance sites around DRC.
Detailed description
This is a phase IV, randomized, open label, 2-arm trial. It will be performed in eight malaria sentinel sites around DRC. Children aged 6 to 59 months with confirmed Plasmodium falciparum uncomplicated malaria will be enrolled after informed consent granted by a parent or guardian. They will be randomized to receive either artesunate-amodiaquine or artemether lumefrantrine during 3 days (directly observed treatment) and then followed up until day 28. At each visit, clinical examination (including collection of safety data) will be done and malaria testing as well. Dried blood spots will also be prepared whenever microscopy is performed, in order to assess resistance markers and perform the genotyping of the parasite for PCR-adjusted efficacy. Hemoglobin level will be measured on the recruitment day and then every two weeks until day 28.
Interventions
Tablets
DRUGArtemether-lumefantrine
Tablets
Sponsors
Centers for Disease Control and Prevention
Global Fund
Ministry of Public Health, Democratic Republic of the Congo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomization 1:1 in two treatment arms: artesunate-amodiaquine and artemether-lumefantrine
Eligibility
Sex/Gender
ALL
Age
6 Months to 59 Months
Healthy volunteers
No
Inclusion criteria
* children aged 6 to 59 months * monoinfection with Plasmodium falciparum with asexual parasite count of 2,000 to 200,000/µL * axillary temperature ≥ 37.5 °C * ability to swallow oral medication * ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule; * informed consent from a parent or a guardian * living within the study catchment area * absence of severe manutrition * absence of infectious diseases that can be responsible of fever * absence of allergy to the study drugs
Exclusion criteria
* presence of general danger signs or signs of severe falciparum malaria according to the definitions of WHO; * body weight \< 5kg * hemoglobin level \< 5g/ dL or hematocrit \< 15% * presence of severe malnutrition * presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS); * regular medication, which may interfere with antimalarial pharmacokinetics; * malaria treatment within 2 days prior to recruitment * history of hypersensitivity reactions or contraindications to any of the medicines being tested or used as alternative treatment; * body weight below 5 kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PCR adjusted efficacy | day 28 | Absence of fever and negative blood smear during the follow-up until day 28 or new infection occurred during the follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of adverse events and serious adverse events | day 28 | Number of adverse events and serious adverse events that every participant will experience |
| Prevalence of HRP2 deletion | Baseline | Proportion of positive samples that fail to be detected by malaria rapid diagnostic tests due to the deletion of the related antigen |
| Prevalence of resistance markers at baseline | Baseline | Proportion of samples containing different markers of resistance to different antimalarial drugs |
| Quantification of Lumefantrine | day 7 | Level of lumefantrine in the blood of children who will be randomized to the Artemether-lumefantrine arm |
Countries
Democratic Republic of the Congo
Outcome results
None listed