Clinical trial NCT00808951: In Vivo and in Vitro Efficacy of Antimalarial Treatments in Children in Burkina Faso
Official title: In Vivo and in Vitro Efficacy of the Recommended First Line Antimalarial Treatments (Artemether-Lumefantrine and Amodiaquine-Artesunate) in Children With Uncomplicated Malaria in Burkina Faso
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria
Keywords: Uncomplicated malaria
P falciparum
Children
National treatment protocol
Burkina Faso
Artemether-lumefantrine
Artesunate-amodiaquine
In vivo efficacy
In vitro efficacy
Lead sponsor: Centre Muraz
Sponsor class: OTHER
Collaborators: name: Institute of Tropical Medicine, Belgium
First posted: 2008-12-16
Enrollment: 440
Sex: ALL
Minimum age (years): 6
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Resistance to antimalarial drugs represents a major obstacle for controlling malaria in endemic countries, so that most sub-Saharan countries have changed their antimalarial drug policy to the new Artemisinin Containing Therapies. Burkina Faso has changed its policy for uncomplicated malaria to Artemether-Lumefantrine (AL) and Artesunate-Amodiaquine (AQ+AS), but there are still little available data on safety and efficacy of these treatments in Burkina Faso; both treatments have shown to be efficacious, but AL seems to have higher occurrence of recurrent malaria infections during a 28-day follow up period. Thus, this study aims at comparing the safety and efficacy of AL and AS-AQ (42-day follow-up), AND also at comparing their in vitro sensitivity, in patients with recurrent infection, with the results obtained in vivo.

Detailed description: Plasmodium falciparum resistance to antimalarial drugs represents the major drawback and obstacle for controlling malaria in endemic countries; that's why most sub-Saharan countries have changed their antimalarial drug policy to Artemisinin Containing Therapies (ACT), which produce a rapid clinical and parasitological cure, reduce gametocyte carriage rate and are generally well tolerated. Burkina Faso has recently changed its policy for the treatment of uncomplicated malaria, from Chloroquine to Artemether-Lumefantrine (AL) and Artesunate-Amodiaquine (AQ+AS). However, there are still little available data on safety and efficacy of these treatments in Burkina Faso; a recent study carried out in Bobo Dioulasso showed that both treatments were extremely efficacious (adjusted treatment failure less than 5%) but with AL showing significantly high occurrence of recurrent infections during the 28-day follow up period. The higher risk for recurrent infections for AL was confirmed in a subsequent trial comparing AL with AQ-SP and dihydroartemisinin-piperaquine, but so far no direct comparison between AQ+AS and AL has been completed, though a study in Nanoro, near Ouagadougou, is ongoing. Thus, the present study aims at comparing the in vivo safety and efficacy of AL and AS-AQ (42-day follow-up),AND at comparing the in vitro sensitivity of the different ACT components, in patients with recurrent infection, with the results obtained in vivo.

Eligibility criteria: Inclusion Criteria:

* Age 6 - 59 months
* Weight \> 5 kg
* Mono-infection with P. falciparum
* Parasitemia of 4,000-200,000 asexual parasites per µl
* Fever: \> 37.5 °C or history of fever in the preceding 24 hours
* Haemoglobin \> 5.0 g/dl
* Signed informed consent by the parents or guardians
* Parents' or guardians' willingness and ability to comply with the study protocol for the duration of the trial.

Exclusion Criteria:

* Participation in any other clinical trial during the previous 30 days
* Known hypersensitivity to the study drugs
* Severe and/or complicated malaria (cases will be referred to Bobo-Dioulasso University hospital for treatment)
* Danger signs: not able to drink or breast-feed, vomiting (\> twice in 24hours), recent history of convulsions (\>1 in 24h), unconscious state, unable to sit or stand;
* Known intercurrent illness or any condition which would place the subject at undue risk or interfere with the results of the study.
* Severe malnutrition (weight for height \<70% of the median NCHS/WHO reference)

Primary outcomes:
measure: PCR unadjusted treatment failure (regardless of genotyping).
timeFrame: 42 days
Secondary outcomes:
measure: PCR adjusted treatment failure
timeFrame: 42 days
measure: PCR unadjusted treatment failure
timeFrame: 28 days
measure: PCR adjusted treatment failure
timeFrame: 28 days
measure: Fever clearance time
timeFrame: day 1, 2, 3
measure: Asexual parasite clearance time
timeFrame: day 7, 14, 21, 28, 35, 42
measure: Gametocytaemia (prevalence and density)
timeFrame: Day 7, 14, 21, 28, 35 and 42
measure: Safety profiles of the two treatments
timeFrame: 42 days overall
measure: Parasites in vitro sensitivity to the drugs tested and their relationship with the in vivo results
timeFrame: before treatment and at the day of reccurrente parasitemia
Other outcomes:
Locations:
city: Bobo-Dioulasso
country: Burkina Faso
facility: Tinto Halidou
state: Houet
Study officials:
affiliation: Centre Muraz
name: Halidou Tinto, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lingani M, Bonkian LN, Yerbanga I, Kazienga A, Valea I, Sorgho H, Ouedraogo JB, Mens PF, Schallig HDFH, Ravinetto R, d'Alessandro U, Tinto H. In vivo/ex vivo efficacy of artemether-lumefantrine and artesunate-amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso. Malar J. 2020 Jan 6;19(1):8. doi: 10.1186/s12936-019-3089-z.