Recruitment

Recruitment Status
Completed

Inclusion Criterias

Lack of danger signs, or no signs of severe and / or complicated malaria according to the WHO definition
Informed consent of parents, guardians or caregivers (legal guardian) after explaining the purpose of the study.
Mono-infection with Plasmodium falciparum in blood, confirmed by microscopy;
...
Lack of danger signs, or no signs of severe and / or complicated malaria according to the WHO definition
Informed consent of parents, guardians or caregivers (legal guardian) after explaining the purpose of the study.
Mono-infection with Plasmodium falciparum in blood, confirmed by microscopy;
Ability to swallow the drugs
Ages 6 to 59 months
Haemoglobin greater than 5.0 g / dl
Absence of a history of hypersensitivity to study medications;
Absence of severe malnutrition;
Axillary temperature ≥ 37.5 C° or history of fever in the last 24 hours;
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;
Parasite density between 2,000 and 200,000 asexual parasites per microliter of blood;
Weight Greater than or equal to 5 kg

Exclusion Criterias

Continuous prophylaxis with cotrimoxazole in HIV positive children
Regular medication that may interfere with the pharmacokinetics of antimalarials;
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)
...
Continuous prophylaxis with cotrimoxazole in HIV positive children
Regular medication that may interfere with the pharmacokinetics of antimalarials;
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)
A history of taking antimalarial drugs or drugs with antimalarial activity in less than 7 days.
History of hypersensitivity or contraindication to study drug;
Multi or mono-infection by another Plasmodium species detected by microscopy;
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 any danger sign or severe or complicated Plasmodium falciparum malaria according to WHO definitions

Summary

Conditions
Malaria
Type
Interventional
Phase
Phase 4
Design
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Younger than 659 years
Gender
Both males and females

Description

This study followed WHO recommendations for in vivo antimalarial efficacy trials. The study population comprised children aged 6 to 59 months with microscopically confirmed acute uncomplicated malaria. Other inclusion criteria included body weight ≥5kg, the presence of fever (≥37.5°C axillary) or a ...

This study followed WHO recommendations for in vivo antimalarial efficacy trials. The study population comprised children aged 6 to 59 months with microscopically confirmed acute uncomplicated malaria. Other inclusion criteria included body weight ≥5kg, the presence of fever (≥37.5°C axillary) or a history of fever in the preceding 24 hours, P. falciparum malaria mono infection with an asexual blood density ≥2,000/µL and <200,000/µL, and the absence of severe signs of complicated malaria as defined by WHO. Key exclusion criteria included mixed malarial infections, haemoglobin <5g/dL, severe malnutrition, intake of anti-malarials within the preceding seven days, ongoing prophylaxis in HIV positive patients with cotrimoxazole or the intake of any other drug with anti-malarial activity, and any serious underlying disease. Patients satisfying the inclusion criteria were enrolled if the parent/guardian signed a detailed written informed consent. Eligible patients were consecutively assigned to the cohort and treated with AL (cohort 1) or AQ-AS (cohort 2). AL (Coartem™) was 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 (Coarsucam™) was 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. All treatments were 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. Antipyretics, such as paracetamol, were used to control fever>=38ºC. In the event of severe malaria or danger signs, the patient was hospitalized and received intravenous quinine, according to the national malaria treatment policy. Rescue therapy according to national malaria treatment guidelines was also administered in cases of early or late treatment failure Follow-up visits took place on days 1, 2, 3, 7, 14, and 28 after enrolment or at any time point whenever the child was sick. Patients who prematurely discontinued either study drug or the study were excluded from the study. Vital signs and body temperature were assessed during each follow-up visit. Adverse events were recorded and assessed for severity and association with study medication. Thick and thin Giemsa-stained blood slides were prepared before each dose was administered and at every follow-up visit of days 2, 3, 7, 14, 21 and 28. Slides were examined by two independent microscopists and considered negative if no parasites were seen after examination of 200 oil-immersion fields in a thick blood film. Species determination (and thus conformation of monoinfection) was made based on assessment of thin films. Blood samples for PCR analysis were collected from every patient at baseline and at days 7, 14 and 28, day of treatment failure or at any other unscheduled visit. PCR was performed centrally for all cases of recurrent parasitaemia from day 7 onwards to distinguish recrudescence from reinfection according to the standardized WHO method

Inclusion Criterias

Lack of danger signs, or no signs of severe and / or complicated malaria according to the WHO definition
Informed consent of parents, guardians or caregivers (legal guardian) after explaining the purpose of the study.
Mono-infection with Plasmodium falciparum in blood, confirmed by microscopy;
...
Lack of danger signs, or no signs of severe and / or complicated malaria according to the WHO definition
Informed consent of parents, guardians or caregivers (legal guardian) after explaining the purpose of the study.
Mono-infection with Plasmodium falciparum in blood, confirmed by microscopy;
Ability to swallow the drugs
Ages 6 to 59 months
Haemoglobin greater than 5.0 g / dl
Absence of a history of hypersensitivity to study medications;
Absence of severe malnutrition;
Axillary temperature ≥ 37.5 C° or history of fever in the last 24 hours;
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;
Parasite density between 2,000 and 200,000 asexual parasites per microliter of blood;
Weight Greater than or equal to 5 kg

Exclusion Criterias

Continuous prophylaxis with cotrimoxazole in HIV positive children
Regular medication that may interfere with the pharmacokinetics of antimalarials;
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)
...
Continuous prophylaxis with cotrimoxazole in HIV positive children
Regular medication that may interfere with the pharmacokinetics of antimalarials;
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)
A history of taking antimalarial drugs or drugs with antimalarial activity in less than 7 days.
History of hypersensitivity or contraindication to study drug;
Multi or mono-infection by another Plasmodium species detected by microscopy;
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 any danger sign or severe or complicated Plasmodium falciparum malaria according to WHO definitions

Locations

Dondo, Sofala
Montepuez, Cabo Delgado
Tete
Manhiça, Maputo, CP1929
Chokwe, Gaza
...
Dondo, Sofala
Montepuez, Cabo Delgado
Tete
Manhiça, Maputo, CP1929
Chokwe, Gaza

Tracking Information

NCT #
NCT02168569
Collaborators
FHI 360
Investigators
Not Provided