Clinical trial NCT04618523: Safety and Efficacy of Recommended Antimalarial 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria
Lead sponsor: Ministry of Public Health, Democratic Republic of the Congo
Sponsor class: OTHER_GOV
Collaborators: name: University of Kinshasa
name: World Health Organization
name: Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
First posted: 2020-11-06
Enrollment: 1117
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Despite all efforts, malaria remains a public health concern, in particular in the Democratic Republic of the Congo (DRC). The National Malaria Control program recommends artemisinin-based combination treatments (ACTs), in particular artesunate-amodiaquine or artemether-lumefrantrine for the treatment of uncomplicated malaria. Previous studies indicated that ACTs are still effective, with efficacy above the required threshold of 90%. It is required to assess regularly the efficacy of antimalarial drugs. I In case of increasing failure rates, alternative options can be decided ontime.

The purpose of this trial is to assess efficacy and safety of artesunate-amodiaquine (ASAQ Winthrop®) and artemether-lumefantrine (Coartem Dispersible®) at day 28 in the treatment of uncomplicated Plasmodium falciparum malaria in six surveillance sites around DRC.

Detailed description: This is a phase IV, randomized, open label, 2-arm trial. It will be performed in six malaria sentinel site around the Democratic Republic of the Congo. 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 will be done and malaria testing as well. Hemoglobin level will be measured on 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 aguardian
* living within the study catchment area

Exclusion Criteria:

* presence of general danger signs in children aged under 5 years 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

Primary outcomes:
measure: PCR adjusted efficacy
timeFrame: 28 days
Secondary outcomes:
measure: Proportion of adverse events and serious adverse events
timeFrame: 28 days
measure: Proportion of participants with positive blood smear at day 3
timeFrame: 3 days
Other outcomes:
measure: Presence of Plasmodium falciparum resistance markers and deletion of HRP2
timeFrame: 28 days
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: Centre de Santé de Référence Mikalayi
state: Kasai-central
city: Kimpese
country: Congo, The Democratic Republic of the
facility: Centre Evangélique de Coopération
state: Kongo Central
city: Rutshuru
country: Congo, The Democratic Republic of the
facility: Centre de Santé de Référence Rutshuru
state: Nord-Kivu
city: Kisangani
country: Congo, The Democratic Republic of the
facility: Centre de Santé Foyer Social
state: Tshopo
city: Boende
country: Congo, The Democratic Republic of the
facility: Centre de Santé Boende 2 Nsele
state: Tshuapa
Study officials:
affiliation: Université de Kinshasa
name: Gauthier Mesia Kahunu, PhD
role: PRINCIPAL_INVESTIGATOR
References: