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

NCT06970600 | Completed

• 2 other identifiers: MEFI_VSUB CONTRACT AGREEMENT #1
• Study Type: interventional
• Target: 352
• Locations: 1 country
• Sites: 4

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.

Conditions

Malaria (Uncomplicated)

Keywords

Efficacy; Artemether-lumefantrine; Mozambique; Malaria

Outcome Measures

Primary Outcomes (1)

• Measuring the Day 28, PCR corrected cure rates of artemether-lumefantrine.

  This cure rate is defined as the proportion of patients with adequate clinical and parasitological response (ACPR) at Day 28, once PCR correction to differentiate recrudescences from new infections have been applied (and hence only considering as treatment failures those parasite recurrences confirmed as recrudescences).

  28 days

Secondary Outcomes (4)

• To evaluate the incidence of adverse events

  28 days

• To evaluate the variation of the levels of haemoglobin during and after treatment

  28 days

• Measuring the Day PCR uncorrected cure rates of Artemether-Lumefantrine.

  28 days

• Evaluate the presence of Molecular Markers associated with sub optimum responses to ACTs

  28 days

Study Arms (1)

Artemether-lumefantrine

OTHER

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.

Drug: Artemether-lumefantrine (Coartem)

Interventions

Artemether-lumefantrine (Coartem) 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.

Artemether-lumefantrine

Eligibility Criteria

• Age: 6 Months - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centro de Investigacao em Saude de Manhica: lead
• World Health Organization (Mozambique): collaborator
• National Malaria Control Program (NMCP), Mozambique: collaborator
• Instituto Nacional de Saúde, Mozambique: collaborator

Study Sites (4)

Hospital Distrital de Massinga

Massinga, Inhambane Province, Mozambique

Location

Hospital Rural de Cuamba

Cuamba, Niassa Province, Mozambique

Location

Hospital Distrital de Dondo

Dondo, Sofala, Mozambique

Location

Hospital Distrital de Mopeia

Mopeia, Zambezia Province, Mozambique

Location

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Pedro Aide, MD, Msc, PhD

  Centro de Investigaçao em Saude de Manhiça

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: May 14, 2025
• Study Start: March 7, 2024
• Primary Completion: October 28, 2024
• Study Completion: January 31, 2025
• Last Updated: May 14, 2025

Record last verified: 2025-05

Locations

MO (4)