Clinical trial NCT02940756: Efficacy and Safety of Artemisinin-based Combination Treatments in the Democratic Republic of the Congo
Official title: Efficacy and Safety of Artesunate-amodiaquine, Artemether-lumefantrine and Dihydroartemisinine-piperaquine in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Democratic Republic of Congo: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria
Keywords: Malaria, efficacy, safety, ACT, DR Congo
Lead sponsor: Ministry of Public Health, Democratic Republic of the Congo
Sponsor class: OTHER_GOV
First posted: 2016-10-21
Enrollment: 1615
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: The Democratic Republic of the Congo (DRC) is among the countries most affected by malaria in Sub-Saharan Africa. Condidering its size and the geographic position, the DRC is meant to play a major role in the malaria control in the region. 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, in order to ascertain the relevance of treatment guidelines such that, 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®), artemether-lumefantrine (Coartem Dispersible®) and dihydro-artemisinin-piperaquine (Eurartesim®) at day 42 in the treatment of uncomplicated Plasmodium falciparum malaria in six surveillance sites around DRC.

Detailed description: This is a phase 4, randomized, open labelled clinical trial, aiming to assess efficacy and safety of 3 ACTs in the treatment of uncomplicated malaria in the Democratic Republic of the Congo. Children diagnosed with uncomplicated Plasmodium falciparum uncomplicated malaria will be randomized and followed-up during 42 days.

Eligibility criteria: Inclusion Criteria:

* children aged 6 to 59 months
* axillary temperature ≥ 37.5 °C or history of fever during the 24 h before recruitment
* monoinfection with Plasmodium falciparum with asexual parasite count of 2,000 to 200,000/µL
* 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/guardian
* absence of general danger signs or signs of severe falciparum malaria according to the definitions of WHO (2000)
* absence of severe malnutrition according to WHO child growth standards
* absence of febrile condition 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 or hepatic diseases, HIV/AIDS)
* absence of regular medication, which might interfere with antimalarial pharmacokinetics
* absence of history of hypersensitivity reactions or contraindication to any medicine being tested or used as alternative treatment

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
* mixed or monoinfection with another Plasmodium species detected by microscopy
* 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;
* history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s)

Primary outcomes:
measure: PCR-adjusted efficacy
timeFrame: day 42
Secondary outcomes:
measure: PCR-unadjusted efficacy
timeFrame: day 42
measure: K-13 propeller polymorphisms
timeFrame: day 42
measure: incidence of adverse events
timeFrame: day 42
Other outcomes:
Locations:
city: Bolenge
country: Congo, The Democratic Republic of the
facility: Centre de santé Bolenge
state: Equateur
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: Kabondo
country: Congo, The Democratic Republic of the
facility: Centre de Santé Foyer Social
state: Tshopo
Study officials:
affiliation: University of Kinshasa
name: Gauthier Mesia Kahunu, PhD
role: PRINCIPAL_INVESTIGATOR
References: