Malaria
Conditions
Keywords
Uncomplicated malaria, P falciparum, Children, National treatment protocol, Burkina Faso, Artemether-lumefantrine, Artesunate-amodiaquine, In vivo efficacy, In vitro efficacy
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.
Interventions
Coformulated AQ+AS by Sanofi-Aventis has been pre-qualified by WHO in 2008. It is administered once daily for three consecutive days, and it is available in three different dosages (25mg/67.5mg; 50mg/135mg; 100mg/270mg)
DRUGArtemether-lumefantrine
Artemether-lumefantrine by Novartis was the first fixed-dose ACT that was prequalified by WHO in April 2004. A 3-day, 6-dose regimen of AL is recommended for infants and children weighing 5-35 kg and adults weighing \> 35 kg.
Sponsors
Institute of Tropical Medicine, Belgium
Centre Muraz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 15 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PCR unadjusted treatment failure (regardless of genotyping). | 42 days |
Secondary
| Measure | Time frame |
|---|---|
| PCR unadjusted treatment failure | 28 days |
| Fever clearance time | day 1, 2, 3 |
| Asexual parasite clearance time | day 7, 14, 21, 28, 35, 42 |
| PCR adjusted treatment failure | 42 days |
| Safety profiles of the two treatments | 42 days overall |
| Parasites in vitro sensitivity to the drugs tested and their relationship with the in vivo results | before treatment and at the day of reccurrente parasitemia |
| Gametocytaemia (prevalence and density) | Day 7, 14, 21, 28, 35 and 42 |
Countries
Burkina Faso
Outcome results
None listed