Clinical trial NCT06970600: Efficacy of Artemether-Lumefantrine in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Children Under 12 Years at Four Sentinel Sites in Mozambique
Official title: Monitoring the Therapeutic Efficacy of Artemether-Lumefantrine Combination in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Children Under 12 Years of Age at Four Sentinel Sites in Mozambique
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria (Uncomplicated)
Keywords: Efficacy
Artemether-lumefantrine
Mozambique
Malaria
Lead sponsor: Centro de Investigacao em Saude de Manhica
Sponsor class: OTHER
Collaborators: name: World Health Organization (Mozambique)
name: National Malaria Control Program (NMCP), Mozambique
name: Instituto Nacional de Saúde, Mozambique
First posted: 2025-05-14
Enrollment: 352
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a classical in vivo clinical trial, following World Health organization's recommendations, ran as a multisite study within Mozambique trying to assess the efficacy and safety in four sites of artemether-lumefantrine (AL) combination for the treatment of uncomplicated malaria in children aged\<12 years. The goal of this study is to evaluate the clinical and parasitological efficacy of the study drug combinations in children aged between 6 - 143 months, suffering from uncomplicated P. falciparum malaria, by determining the proportion with early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF) or an adequate clinical and parasitological response (ACPR) as indicators of efficacy. The participants will take AL for three days and followed-up for 28 days.

Detailed description: Eligible patients were consecutively assigned to the cohort and treated with AL. AL (Coartem™) will be administered twice daily for three days (six doses in total) with dosage determined according to body weight: one tablet (20mg artemether and 120mg lumefantrine) for children 5 to \<15kg, two tablets per dose for those 15 to \<25kg, and three tablets per dose for those 25 to \<35kg. All treatments will be directly observed for a minimum of 30 minutes. Vomiting occurring within the first 30 minutes implied the repetition of the full dose of treatment. For those patients living far away from the health facilities, and for which direct observation of the evening doses of AL was challenging, admission was offered for the first three days of the study. Then after first four days, the patients were followed-up weekly ( clinical and laboratory assessment) until day 28.

Eligibility criteria: Inclusion Criteria:

* Ages 6 to 143 months
* Weight Greater than or equal to 5 kg
* Absence of severe malnutrition;
* Mono-infection with Plasmodium falciparum in blood, confirmed by microscopy;
* Parasite density between 1,000 and 200,000 asexual parasites per microliter of blood;
* Haemoglobin ≥ 7.0 g/dl;
* Axillary temperature ≥ 37.5 C° or history of fever in the last 24 hours;
* Lack of danger signs, or no signs of severe and / or complicated malaria according to the WHO definition
* Ability to swallow the drugs
* Residents within the study area and have the possibility of an adequate follow-up in the days of monitoring for a period of 28 days;
* Absence of a history of hypersensitivity to study medications;
* Informed consent of parents, guardians or caregivers (legal guardian) after explaining the purpose of the study.

Exclusion Criteria:

* Presence of any danger sign or severe or complicated Plasmodium falciparum malaria according to WHO definitions;
* Presence of fever due to diseases other than malaria (eg measles, acute respiratory infection, severe diarrhea with dehydration) or other known diseases, with chronic or serious illnesses (cardiac, renal, hepatic or known infection with HIV AIDS);
* Presence of severe malnutrition (defined as a child whose growth pattern is below the 3rd percentile, mid-upper-arm circumference \<110mm, weight / height \<70% according to the WHO tables, or the presence of bilateral edema of the lower limbs);
* Multi or mono-infection by another Plasmodium species detected by microscopy;
* Regular medication that may interfere with the pharmacokinetics of antimalarials;
* History of hypersensitivity or contraindication to study drug;
* A history of taking antimalarial drugs or drugs with antimalarial activity in less than 7 days.
* Continuous prophylaxis with cotrimoxazole in HIV positive children.

Primary outcomes:
measure: Measuring the Day 28, PCR corrected cure rates of artemether-lumefantrine.
timeFrame: 28 days
Secondary outcomes:
measure: To evaluate the incidence of adverse events
timeFrame: 28 days
measure: To evaluate the variation of the levels of haemoglobin during and after treatment
timeFrame: 28 days
measure: Measuring the Day PCR uncorrected cure rates of Artemether-Lumefantrine.
timeFrame: 28 days
measure: Evaluate the presence of Molecular Markers associated with sub optimum responses to ACTs
timeFrame: 28 days
Other outcomes:
Locations:
city: Massinga
country: Mozambique
facility: Hospital Distrital de Massinga
state: Inhambane
city: Cuamba
country: Mozambique
facility: Hospital Rural de Cuamba
state: Niassa
city: Dondo
country: Mozambique
facility: Hospital Distrital de Dondo
state: Sofala
city: Mopeia
country: Mozambique
facility: Hospital Distrital de Mopeia
state: Zambezia
Study officials:
affiliation: Centro de Investigaçao em Saude de Manhiça
name: Pedro Aide, MD, Msc, PhD
role: PRINCIPAL_INVESTIGATOR
References: