Efficacy of Artemether-Lumefantrine in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Children Under 12 Years at Four Sentinel Sites in Mozambique

NCT ID: NCT06970600

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 352 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-07
• Study Completion Date: 2025-01-31

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.

Conditions

Malaria (Uncomplicated)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Artemether-lumefantrine

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.

Group Type: OTHER

Artemether-lumefantrine (Coartem)

Intervention Type: DRUG

Eligible patients will be consecutively assigned to the four cohorts. Rescue therapy according to national malaria treatment guidelines will be also administered in cases of early or late treatment failure. Follow-up visits will take place on days 1, 2, 3, 7, 14,21 and 28 after enrolment or at any time point whenever the child is sick. Adverse events will be recorded and assessed for severity and association with study medication. Thick and thin Giemsa-stained blood slides will be prepared before each dose to be administered and at every follow-up visit of days 2, 3, 7, 14, 21, 28, 35 and 42. Blood samples for PCR analysis will be collected from every patient at baseline and at days 7, 14, 28, and 42 day of treatment failure or at any other unscheduled visit. To differentiate recrudescence from new infection by polymerase chain reaction (PCR) analysis.The Molecular markers associated with suboptimal response to ACTs will be investigated.

Interventions

Artemether-lumefantrine (Coartem)

Eligible patients will be consecutively assigned to the four cohorts. Rescue therapy according to national malaria treatment guidelines will be also administered in cases of early or late treatment failure. Follow-up visits will take place on days 1, 2, 3, 7, 14,21 and 28 after enrolment or at any time point whenever the child is sick. Adverse events will be recorded and assessed for severity and association with study medication. Thick and thin Giemsa-stained blood slides will be prepared before each dose to be administered and at every follow-up visit of days 2, 3, 7, 14, 21, 28, 35 and 42. Blood samples for PCR analysis will be collected from every patient at baseline and at days 7, 14, 28, and 42 day of treatment failure or at any other unscheduled visit. To differentiate recrudescence from new infection by polymerase chain reaction (PCR) analysis.The Molecular markers associated with suboptimal response to ACTs will be investigated.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

World Health Organization (Mozambique)

UNKNOWN

Sponsor Role: collaborator

National Malaria Control Program (NMCP), Mozambique

UNKNOWN

Sponsor Role: collaborator

Instituto Nacional de Saúde, Mozambique

OTHER_GOV

Sponsor Role: collaborator

Centro de Investigacao em Saude de Manhica

OTHER

Sponsor Role: lead

Responsible Party

Pedro Aide

PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pedro Aide, MD, Msc, PhD

Role: PRINCIPAL_INVESTIGATOR

Centro de Investigaçao em Saude de Manhiça

Locations

Hospital Distrital de Massinga

Massinga, Inhambane Province, Mozambique

Hospital Rural de Cuamba

Cuamba, Niassa Province, Mozambique

Hospital Distrital de Dondo

Dondo, Sofala, Mozambique

Hospital Distrital de Mopeia

Mopeia, Zambezia Province, Mozambique

Countries

Mozambique

Other Identifiers

SUB CONTRACT AGREEMENT #1

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

MEFI_V

Identifier Type: -

Identifier Source: org_study_id