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

This study has been completed.
Sponsor:
Information provided by:
Centre Muraz
ClinicalTrials.gov Identifier:
NCT00808951
First received: December 5, 2008
Last updated: June 9, 2011
Last verified: February 2009
  Purpose

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.


Condition Intervention Phase
Uncomplicated P. Falciparum Malaria in Children
Drug: Artesunate-amodiaquine
Drug: Artemether-lumefantrine
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Centre Muraz:

Primary Outcome Measures:
  • PCR unadjusted treatment failure (regardless of genotyping). [ Time Frame: 42 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PCR adjusted treatment failure [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • PCR unadjusted treatment failure [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • PCR adjusted treatment failure [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Fever clearance time [ Time Frame: day 1, 2, 3 ] [ Designated as safety issue: No ]
  • Asexual parasite clearance time [ Time Frame: day 7, 14, 21, 28, 35, 42 ] [ Designated as safety issue: No ]
  • Gametocytaemia (prevalence and density) [ Time Frame: Day 7, 14, 21, 28, 35 and 42 ] [ Designated as safety issue: No ]
  • Safety profiles of the two treatments [ Time Frame: 42 days overall ] [ Designated as safety issue: Yes ]
  • Parasites in vitro sensitivity to the drugs tested and their relationship with the in vivo results [ Time Frame: before treatment and at the day of reccurrente parasitemia ] [ Designated as safety issue: No ]

Estimated Enrollment: 440
Study Start Date: December 2008
Study Completion Date: February 2011
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Artemether -lumefantrine
Treatment of malaria with Artemether-lumefantrine (AL), according to one of the two options given by national protocol in Burkina Faso
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.
Other Name: AL, Coartem(R), Riamet(R)
Experimental: Artesunate-amodiaquine
Treatment of malaria with Artesunate-amodiaquine(AS-AQ), according to one of the two options given by national protocol in Burkina Faso
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)
Other Name: ASAQ, Coarsucam

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

Ages Eligible for Study:   6 Months to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00808951

Locations
Burkina Faso
Tinto Halidou
Bobo-Dioulasso, Houet, Burkina Faso, 01
Sponsors and Collaborators
Centre Muraz
  More Information

Additional Information:
No publications provided

Responsible Party: Tinto Halidou, IRSS/Centre Muraz
ClinicalTrials.gov Identifier: NCT00808951     History of Changes
Other Study ID Numbers: Malactres-BF
Study First Received: December 5, 2008
Last Updated: June 9, 2011
Health Authority: Burkina Faso: Ministry of Health

Keywords provided by Centre Muraz:
Uncomplicated malaria
P falciparum
Children
National treatment protocol
Burkina Faso
Artemether-lumefantrine
Artesunate-amodiaquine
In vivo efficacy
In vitro efficacy

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Parasitic Diseases
Protozoan Infections
Amodiaquine
Antimalarials
Artemether
Artemether-lumefantrine combination
Artemisinins
Artesunate
Lumefantrine
Amebicides
Anthelmintics
Anti-Infective Agents
Antifungal Agents
Antiparasitic Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Coccidiostats
Pharmacologic Actions
Schistosomicides
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014