In Vivo Efficacy of Artemether-lumefantrine and Amodiaquine-artesunate in Mozambican Children (MEFI)
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|ClinicalTrials.gov Identifier: NCT02168569|
Recruitment Status : Completed
First Posted : June 20, 2014
Last Update Posted : June 20, 2014
|Condition or disease||Intervention/treatment||Phase|
|Malaria||Drug: Coartem™ (Artemether-lumefantrine combination) Drug: Coarsucam™ (Amodiaquine-artesunate combination)||Phase 4|
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
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||700 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||In Vivo Efficacy of Artemether-lumefantrine and Amodiaquine-artesunate for the Treatment of Uncomplicated Falciparum Malaria in Children: A Multisite, Open-label, Two-cohort Clinical Trial in Mozambique.|
|Study Start Date :||June 2011|
|Actual Primary Completion Date :||January 2012|
|Actual Study Completion Date :||January 2013|
Active Comparator: Cohort 1
5 sites, namely Manhiça, Dondo, Montepuez, Tete and Chokwe
Drug: Coartem™ (Artemether-lumefantrine combination)
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.
Active Comparator: Cohort 2
3 sites, namely Montepuez, Dondo and Chokwe
Drug: Coarsucam™ (Amodiaquine-artesunate combination)
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.
- To measure the Day 28, PCR corrected cure rates of artemether-lumefantrine (Coartem) and Amodiaquine-artesunate (Coarsucam). [ Time Frame: 28 days ]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 friom new infections have been applied (and hence only considering as treatment failures those parasite recurrences confirmed as recrudescences).
- to evaluate the incidence of adverse events [ Time Frame: 28 days ]To evaluate the incidence of adverse events, including the variation of haemoglobin levels throughout follow-up, during the 28 days that each subject will be followed
- PCR uncorrected Day 28 efficacy of AL and AQ-AS [ Time Frame: 28 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02168569
|Hospital Rural de Montepuez|
|Montepuez, Cabo Delgado, Mozambique|
|Hospital Rural de Chókwe,|
|Chokwe, Gaza, Mozambique|
|Centro de Investigação em Saúde de Manhiça|
|Manhiça, Maputo, Mozambique, CP1929|
|Centro de Saúde de Dondo|
|Dondo, Sofala, Mozambique|
|Hospital Provinvial de Tete|