Artemisinin-Based Combination Therapy: Clinical Trials in Cameroon
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 3

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
    

Intervention name(s): 1. Artemether-Lumefantrine (AL); 2. Amodiaquine-Artesunate (AQ-AS)
Intervention type(s): Drug; Drug
Intervention description(s): Artemether-Lumefantrine(Co-Artem)=Artemether, 2mg/kg x 2(12h apart) and Lumefantrine, 12mg/kgx2 (12h apart).; Amodiaquine-Artesunate (0H),D1(24H),D2(48H)= Artesunate 4mg/kg and Amodiaquine at 10mg/kg
Other intervention name(s): CoArtem; Arsucam
Intervention MeSH terms: Artesunate; Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination; Amodiaquine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Efficacy; Safety; Children; Cameroon