In Vivo and in Vitro Efficacy of Antimalarial Treatments in Children in Burkina Faso

Malaria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00808951
• Other study ID #: Malactres-BF
• Status: Completed
• Phase: Phase 4
• First received: December 5, 2008
• Last updated: July 30, 2015
• Start date: December 2008
• Est. completion date: February 2011

Study information

• Verified date: July 2015
• Source: Centre Muraz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Burkina Faso: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 440
• Est. completion date: February 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 15 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Artesunate-amodiaquine
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)
• Artemether-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.

Locations

Country	Name	City	State
Burkina Faso	Tinto Halidou	Bobo-Dioulasso	Houet

Sponsors (2)

Lead Sponsor	Collaborator
Centre Muraz	Institute of Tropical Medicine, Belgium

Country where clinical trial is conducted

Burkina Faso, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PCR unadjusted treatment failure (regardless of genotyping).		42 days	No
Secondary	PCR adjusted treatment failure		42 days	No
Secondary	PCR unadjusted treatment failure		28 days	No
Secondary	PCR adjusted treatment failure		28 days	No
Secondary	Fever clearance time		day 1, 2, 3	No
Secondary	Asexual parasite clearance time		day 7, 14, 21, 28, 35, 42	No
Secondary	Gametocytaemia (prevalence and density)		Day 7, 14, 21, 28, 35 and 42	No
Secondary	Safety profiles of the two treatments		42 days overall	Yes
Secondary	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	No