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

NCT ID: NCT00808951

Last Updated: 2015-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2011-02-28

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.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Artemether -lumefantrine

Treatment of malaria with Artemether-lumefantrine (AL), according to one of the two options given by national protocol in Burkina Faso

Group Type: EXPERIMENTAL

Artemether-lumefantrine

Intervention Type: DRUG

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.

Artesunate-amodiaquine

Treatment of malaria with Artesunate-amodiaquine(AS-AQ), according to one of the two options given by national protocol in Burkina Faso

Group Type: EXPERIMENTAL

Artesunate-amodiaquine

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

ASAQ, Coarsucam; AL, Coartem(R), Riamet(R)

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)

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role: collaborator

Centre Muraz

OTHER

Sponsor Role: lead

Responsible Party

Tinto Halidou

PharmD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Halidou Tinto, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Muraz

Locations

Tinto Halidou

Bobo-Dioulasso, Houet, Burkina Faso

Countries

Burkina Faso

References

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.

Reference Type: DERIVED

PMID: 31906948 (View on PubMed)

Other Identifiers

Malactres-BF

Identifier Type: -

Identifier Source: org_study_id