Clinical trial NCT00297882: Artemisinin-Based Combination Therapy: Clinical Trials in Cameroon
Official title: Phase III Clinical Trials of Artemisinin-based Combination Therapy in Cameroon
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria
Keywords: Efficacy
Safety
Children
Cameroon
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: University of Yaounde
name: Cameroon Baptist Convention Health
First posted: 2006-03-01
Enrollment: 816
Sex: ALL
Minimum age (years): 6
Maximum age (years): 120
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This proposal aims to evaluate the safety and efficacy of artemisinin-based anti-malaria combination drugs (ACTs) for the treatment of children aged 6-120 months in different locations in Cameroon. Randomized clinical trials will provide local data on the safety of the test drugs, and on putative marker mutations of the development of resistance to ACT. The study will involve three centers, namely, Banso (Guinea-Savannah region), Limbe(Littoral Forest), and Garoua(Sahel-Savannah). The trial will compare the efficacy and safety of Amodiaquine(AQ)-Artesunate(Art) with Coartem®(Artemether-Lumefantrine). Drug efficacy will be determined using a WHO standardized 28-day protocol. Safety will be monitored through clinical examination and biochemical and hematological indices. Molecular markers of artemisinin resistance will be investigated by molecular sequencing and comparison of parasite profiles of the PfATP6 gene in drug failure cases, . Recrudescences or re-infections will be assessed by analysis of the msp1 and msp2 genes. The impact of these combinations on generation of gametocytes will be determined from gametocyte carriage rates measured by microscopy.

Detailed description: * Outpatients will be screened for malaria by blood film examination
* Malaria-positive children will be examined by the physician for inclusion or exclusion(see below)
* Informed consent will be sought from the guardians of potential patients
* Patients or guardians will be interviewed and a case record form completed
* Patients will be randomized into one of the two arms in the ratio 4:1 AQ/Art: CoArtem and issued a study card
* Filter paper and 5ml venous blood samples will be collected
* Patients will be hospitalised for three days to allow completion of therapy under observation
* The patient will be asked to return on days 7, 14 and 28 for assessment of clearance or recrudescence of parasites
* Patient will be examined for parasites and evaluated for early treatment failure (ETF), late treatment failure (LTF), late parasitological failure (LPF) or adequate clinical and parasitological response.(ACPR).
* If a patient does not appear for follow up, a community health worker will try to trace them and will collect blood onto filter paper and a microscope slide should the patient have a temperature ≥ 37.5°C
* Patients whose parents opt out of the study will be administered quinine sulphate if parasitaemic
* Filter paper samples will be air dried and stored with dessicant until required.
* Whole blood samples collected into citrate as anticoagulant will be processed for plasma, aliquoted into 300µl lots and stored at -70°C.
* Patient information will be entered at the close of each day into laptops and collectively sent to Yaounde at the end of the first month of study and thereafter at the end of each week, along with the hard copies of the case report forms.
* Analysis will be performed on the samples within three months of collection for molecular markers of resistance, genetic structure of parasites and for blood drug levels of medications used in the trial

Eligibility criteria: Inclusion criteria:

* children aged 6-120 months;
* axillary temperature ≥ 37.5°C and/or history of fever within past 24 hours;
* P. falciparum asexual parasitemia between 1000 and 100000/µl;
* ability to attend follow-up visits.

Exclusion criteria:

* co-infections;
* underlying chronic disease;
* severe malaria as indicated by hyperparasitemia, severe anemia (PCV 15%, Hb 5g/ml), respiratory distress, inability to drink, persistent vomiting in past 24 hours;
* recent history of multiple convulsions;
* jaundice;
* the inability to stand or sit;
* history of allergy to study drugs.

Primary outcomes:
measure: Cure Rate on Day 28
timeFrame: Day 0 - 28
Secondary outcomes:
measure: Cure Rate Day 14
timeFrame: Day 0-14
Other outcomes:
Locations:
Study officials:
affiliation: University of Yaounde
name: Wilfred F Mbacham, ScD
role: PRINCIPAL_INVESTIGATOR
References: