In Vivo Efficacy of Artemether-Lumefantrine, Amodiaquine-Artesunate, Dihydroartemisinin-Piperaquine, and Pironaridine-Artesunate in Mozambique

NCT ID: NCT05343312

Last Updated: 2025-08-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

870 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-16

Study Completion Date

2025-07-30

Brief Summary

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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

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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.

Conditions

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Malaria

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Artemether-Lumefantrine (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.

Group Type ACTIVE_COMPARATOR

AL (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. The Molecular markers associated with suboptimal response to ACTs will be investigated.

Amodiaquine-Artesunate (AS-AQ)

AQ-AS (Coarsucam™) 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.

Group Type ACTIVE_COMPARATOR

AS-AQ (Carsucam)

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, 28, 35 and 42 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, and 28 day of treatment failure or at any other unscheduled visit. The Molecular markers associated with suboptimal response to ACTs will be investigated.

Dihydroartimisin+Piperaquine (DHP)

DHP will be administered once daily according to body weight: tablet (40 mg dihydroartimisin+artesunate) half in children 5 \< 10kg, one in children 10 \< 20kg and 2 tablets for those children over 20 kg.

Group Type ACTIVE_COMPARATOR

DHP

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, 28, 35 and 42 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. The Molecular markers associated with suboptimal response to ACTs will be investigated.

Pyronaridine +Artesunate (PA)

PA will be administered once daily according to body weight: granule ( 60 mg pyronaridine + 20 artesunate), one in children 5 \< 7kg, two in children 8 \< 15kg and three in children 15 \< 20kg. Tablets ( 180 mg pyronaridine+ 60 mg artesunate), one in children 20 \< 24Kg and two in children 24 \< 45Kg.

Group Type ACTIVE_COMPARATOR

PA

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, 28, 35 and 42 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. The Molecular markers associated with suboptimal response to ACTs will be investigated.

Interventions

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AL (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. The Molecular markers associated with suboptimal response to ACTs will be investigated.

Intervention Type DRUG

AS-AQ (Carsucam)

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, 28, 35 and 42 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, and 28 day of treatment failure or at any other unscheduled visit. The Molecular markers associated with suboptimal response to ACTs will be investigated.

Intervention Type DRUG

DHP

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, 28, 35 and 42 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. The Molecular markers associated with suboptimal response to ACTs will be investigated.

Intervention Type DRUG

PA

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, 28, 35 and 42 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. The Molecular markers associated with suboptimal response to ACTs will be investigated.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

6 Months

Maximum Eligible Age

59 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United States Agency for International Development (USAID)

FED

Sponsor Role collaborator

Centro de Investigacao em Saude de Manhica

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hospital Rural de Montepuez

Montepuez, Cabo Delgado Province, Mozambique

Site Status

Hospital Distrital de Mssinga

Massinga, Inhambane Province, Mozambique

Site Status

Hospital Distrital de Dondo

Dondo, Sofala, Mozambique

Site Status

Mospital Distrital de Moatize

Moatize, Tete, Mozambique

Site Status

Hospital Distrital de Mopeia

Mopeia, Zambezia Province, Mozambique

Site Status

Countries

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Mozambique

References

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Nhama A, Chidimatembue A, Nhamussua L, Bassat Q, da Silva C, Nhacolo A, Arnaldo P, Salvador C, Cassy A, Candrinho B, Dimene M, Carvalho E, Saifodine A, Wate F, Mucavele H, Torres-Mendoza Y, Horton B, Plucinski M, Cistero P, Mayor A, Aide P. Efficacy of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in Mozambique, 2022. Malar J. 2025 Jul 14;24(1):231. doi: 10.1186/s12936-025-05473-9.

Reference Type DERIVED
PMID: 40660279 (View on PubMed)

Related Links

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Other Identifiers

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20/CNBS/22

Identifier Type: -

Identifier Source: org_study_id

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