Clinical trial NCT06076213: Test Efficacy Study on the Recommended Antimalarial Drugs in the Democratic Republic of the Congo
Official title: Efficacy and Safety of Artesunate-amodiaquine and Artemether-lumefantrine in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Democratic Republic of the Congo: a Randomized Controlled Trial (TES2022)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Uncomplicated Plasmodium Falciparum Malaria
Keywords: Uncomplicated malaria
Plasmodium falciparum
Artemisinin-based Combination Treatment
Artemether-lumefantrine
Artesunate-amodiaquine
Lead sponsor: Ministry of Public Health, Democratic Republic of the Congo
Sponsor class: OTHER_GOV
Collaborators: name: Centers for Disease Control and Prevention
name: Global Fund
First posted: 2023-10-10
Enrollment: 1260
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization 1:1 in two treatment arms: artesunate-amodiaquine and artemether-lumefantrine
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: PCR adjusted efficacy
timeFrame: day 28
Secondary outcomes:
measure: Proportion of adverse events and serious adverse events
timeFrame: day 28
measure: Prevalence of HRP2 deletion
timeFrame: Baseline
measure: Prevalence of resistance markers at baseline
timeFrame: Baseline
measure: Quantification of Lumefantrine
timeFrame: day 7
Other outcomes:
Locations:
city: Kapolowe
country: Congo, The Democratic Republic of the
facility: Centre de santé Lupidi 1
state: Haut-Katanga
city: Kazumba
country: Congo, The Democratic Republic of the
facility: Centres de santé de Mikalayi et Matamba
state: Kasai Central
city: Kimpese
country: Congo, The Democratic Republic of the
facility: Centre de santé de Coopération
state: Kongo Central
city: Vanga
country: Congo, The Democratic Republic of the
facility: Centre de Santé de Vanga
state: Kwilu
city: Kalima
country: Congo, The Democratic Republic of the
facility: Centre de santé de Kalima
state: Maniema
city: Kabondo
country: Congo, The Democratic Republic of the
facility: Centres de santé Umoja et Foyer social
state: Tshopo
city: Boende
country: Congo, The Democratic Republic of the
facility: Centre de santé Boende 2 Nsele
state: Tshuapa
Study officials:
References: