Clinical trial NCT05343312: In Vivo Efficacy of Artemether-Lumefantrine, Amodiaquine-Artesunate, Dihydroartemisinin-Piperaquine, and Pironaridine-Artesunate in Mozambique
Official title: Monitoring the Therapeutic Efficacy of the Combinations Artemether-Lumefantrine, Amodiaquine-Artesunate, Dihydroartemisinin-Piperaquine, and Pironaridine-Artesunate in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Children Under 5 Years of Age in Five Sentinel Sites in Mozambique
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Malaria
Keywords: Treatment
Artemisine-based combinations
children
Lead sponsor: Centro de Investigacao em Saude de Manhica
Sponsor class: OTHER
Collaborators: name: United States Agency for International Development (USAID)
First posted: 2022-04-25
Enrollment: 870
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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 5 sites of the four oral ACTS artemether-lumefantrine (AL), Amodiaquine-Artesunate (AQ-AS), Dihydroartemisinin-Piperaquine (DHP) and Pironaridine-Artesunate for the treatment of uncomplicated malaria in children aged\<5 years.

Detailed description: Eligible patients were consecutively assigned to the cohort and treated with AL (cohort 1), AQ-AS (cohort 2), DHP (cohort 3) and PA (cohort 4). 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. AQ-AS (Winthrop™) will be administered once daily according to body weight: one 25mg artesunate and 67.5mg amodiaquine tablet in children \<9kg, one 50mg artesunate and 135mg amodiaquine tablet in children 9-17.9kg; and one 100mg artesunate and 270mg amodiaquine tablet in children \>18-35kg. DHP will be administered once daily according to body weight: half tablet (40mg dihydroartemisinin e 320 mg piperaquine) for children 5 to \< 10Kg, one tablet for per dose for those 10 \< 20Kg and 2 tablets for 20 or more Kg. PA (granules 60mg pirinaridine +/20mg artesunate) will administered once daily according to body weight: 1 granule per dose for children 5 to \< 8Kg, two for children 8 \< 15Kg, three for those 15 \< 20Kg. PA (180mg pyrinaridine+60 mg artesunate) one tablet for children 20 \< 24Kg and two tablets for those 24 \< 45Kg. 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.

Eligibility criteria: Inclusion Criteria:

* Ages 6 to 59 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 2,000 and 200,000 asexual parasites per microliter of blood;
* 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
* Haemoglobin greater than 5.0 g / dl
* 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: To measure the Day 28, PCR corrected cure rates of artemether-lumefantrine and Amodiaquine-artesunate.
timeFrame: 28 days
measure: To measure the Day 42, PCR corrected cure rates of Dihydroartemisinin-Piperaquine and Pironaridine-Artesunate
timeFrame: 42 days
Secondary outcomes:
measure: To evaluate the incidence of adverse events
timeFrame: 28/42 days
measure: To measure the Day PCR uncorrected cure rates of Artemether-Lumefantrine, Amodiaquine-Artesunate, Dihydroartemisinin-Piperaquine, and Pironaridine-Artesunate.
timeFrame: 28/42 days
measure: Evaluate the presence of Molecular Markers associated with sub optimum responses to ACTs
timeFrame: 28/42 days
Other outcomes:
Locations:
city: Montepuez
country: Mozambique
facility: Hospital Rural de Montepuez
state: Cabo Delgado
city: Massinga
country: Mozambique
facility: Hospital Distrital de Mssinga
state: Inhambane
city: Dondo
country: Mozambique
facility: Hospital Distrital de Dondo
state: Sofala
city: Moatize
country: Mozambique
facility: Mospital Distrital de Moatize
state: Tete
city: Mopeia
country: Mozambique
facility: Hospital Distrital de Mopeia
state: Zambezia
Study officials:
References: