Ignite Creation Date:
2024-05-06 @ 2:38 PM
Last Modification Date:
2024-10-26 @ 1:34 PM
Study NCT ID:
NCT04370977
Status:
COMPLETED
Last Update Posted:
2020-05-01
First Post:
2020-04-09
Brief Title:
In Vivo Efficacy of Artemether-lumefantrine and Amodiaquine-artesunate in Mozambican Children MEFI_III
Sponsor:
Centro de Investigacao em Saude de Manhica
Organization:
Centro de Investigacao em Saude de Manhica
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2020-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MEFI_III
Brief Summary:
This is a classical in vivo clinical trial following World Health organizations recommendations ran as a multisite study within Mozambique trying to assess the efficacy and safety in 4 sites of the two oral ACTS artemether-lumefantrine AL and Amodiaquine-Artesunate AQ-AS first line treatment for malaria in mozambique for the treatment of uncomplicated malaria in children aged5 years
Detailed 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 375C axillary or a history of fever in the preceding 24 hours P falciparum malaria mono infection with an asexual blood density 2000µL and 200000µL and the absence of severe signs of complicated malaria as defined by WHO Key exclusion criteria included mixed malarial infections haemoglobin 5gdL 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 parentguardian 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 Winthrop was administered once daily according to body weight one 25mg artesunate and 675mg amodiaquine tablet in children 9kg one 50mg artesunate and 135mg amodiaquine tablet in children 9-179kg 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 fever38ºC 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 The Molecular markers associated with suboptimal response to ACTs will be investigated
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 375C axillary or a history of fever in the preceding 24 hours P falciparum malaria mono infection with an asexual blood density 2000µL and 200000µL and the absence of severe signs of complicated malaria as defined by WHO Key exclusion criteria included mixed malarial infections haemoglobin 5gdL 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 parentguardian 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 Winthrop was administered once daily according to body weight one 25mg artesunate and 675mg amodiaquine tablet in children 9kg one 50mg artesunate and 135mg amodiaquine tablet in children 9-179kg 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 fever38ºC 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 The Molecular markers associated with suboptimal response to ACTs will be investigated
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None