Longitudinal Antimalarial Combinations in Uganda
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to compare different ways of treating uncomplicated malaria in a
      group of Ugandan children. The study will be divided into 2 parts. Part 1 of the study will
      consist of 600 children, ages 1-10, living in the Mulago III Parish of Kampala. Approximately
      90 children living in the same household as children from the Phase 1 portion of the study
      will be enrolled in Phase II of this study. Participants in Phase II of the study will
      receive an insecticide treated net to cover their bed. Over the course of the study,
      participants will be tested for malaria when they present to the clinic with a fever or
      illness. Participants that test positive for malaria will be given 1 of 3 possible study drug
      combinations. Study procedures will include physical exams and blood samples. Children will
      participate for about 3 years. Protocol 05-0110 is a study related to this protocol.
    

Detailed description: 
      Malaria is one of the most important infectious diseases worldwide. New therapies are needed,
      and it is generally agreed that combination therapy for uncomplicated malaria offers the best
      opportunity for effective therapy and for the prevention of selection of resistant parasites.
      Phase I of this study will be a randomized, single-blinded longitudinal clinical trial,
      comparing the efficacies of different combination antimalarial regimens for the treatment of
      uncomplicated malaria in a cohort of Ugandan children. The clinical study will be linked to
      an epidemiological survey and molecular analyses of parasite and human genetic polymorphisms.
      The aims of the study will be to: compare safety, tolerability, and efficacy of combination
      antimalarial therapies using a longitudinal design; follow plasmodial genetic polymorphisms
      as longitudinal markers of antimalarial drug resistance; and evaluate the roles of host
      genetic polymorphisms in antimalarial drug resistance and the incidence of clinical malaria.
      The clinical study will recruit participants from a defined and mapped source population in
      the Mulago III Parish, Kawempe District in Kampala, Uganda; conduct a survey of
      epidemiological factors on participants; and follow clinical care and outcomes over an
      extended period of time. Molecular analyses of parasite and human genetic polymorphisms will
      evaluate the impact of parasite mutations on treatment efficacy, the effects of repeated
      treatments on selection for resistance-mediating genotypes, and the impact of host
      polymorphisms on the incidence of malaria and responses to therapy. Phase I will include a
      random sample of 600 Ugandan children between the ages of 1-10 years. Participants will be
      followed for 3 years for all routine medical care in the study clinic at Mulago Hospital.
      Children presenting to the study clinic with a new episode of fever will undergo standard
      evaluation (history, physical examination and Giemsa-stained blood smear) for the diagnosis
      of malaria. Participants will be randomized to one of three combination treatment regimens at
      the time of their first diagnosis of uncomplicated malaria. Subsequent episodes of
      uncomplicated malaria will be treated with each participant's assigned treatment regimen.
      Clinical treatment failures occurring within 14 days of diagnosis and all episodes of
      complicated malaria will be treated with quinine, the standard therapy for malaria after
      treatment failure in Uganda. Routine home visits will be made for participants not seen in
      the clinic after any consecutive 30-day period. Routine home visits, made every 90 days, will
      include review of study protocol with the participants, assessment for any outside medical
      care, a focused history and physical examination and routine laboratory testing. Phase II
      will be a randomized, open-label, longitudinal clinical trial, comparing two combination
      antimalarial regimens. Following the first year of follow up, recruitment will be re-opened
      for children belonging to the same households previously recruited to the study, for children
      not previously enrolled ages 1-10 years. At this time, all participants will receive an
      insecticide treated bed net and phase II follow up will begin. All other aspects of subject
      evaluation, management, and follow-up will be the same as in Phase I, except that researchers
      will discontinue 30 day finger sticks (subjects will still be visited if they have not been
      seen in the clinic for 30 days, but finger sticks for blood smears and filter paper will only
      be performed during clinic evaluations, when clinically indicated or if the patient has not
      been evaluated in the clinic over a 90 day period). The primary outcome and endpoint (power
      calculations are based only on this endpoint) for this study will be treatment incidence
      density (treatments per time at risk) for each treatment arm. Secondary outcomes include drug
      efficacy and safety and tolerability. Protocol 05-0110 is a sub study of this protocol.
    

Intervention name(s): Amodiaquine+Artesunate; Amodiaquine+Sulfadoxine/Pyrimethamine; Artemether+Lumefantrine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Amodiaquine 10 mg/kg on day 1, then 5 mg/kg on day 2 and 3; Artesunate 4 mg/kg/d for three days; Amodiaquine 10 mg/kg on day 1, then 5 mg/kg on day 2 and 3; S/P at 25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine single dose; Artemether 20 mg + Lumefantrine 120 mg 6 dose regimen at 0 and 8 hours on day 1 and twice daily on days 2 and 3:5 kg to < 15 kg: 1 tab/dose; 15 to 24 kg: 2 tabs/dose; >35 kg:4 tabs per dose
Intervention MeSH terms: Artesunate; Lumefantrine; Pyrimethamine; Artemether; Sulfadoxine; Amodiaquine; Artemether, Lumefantrine Drug Combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Care Provider)
Primary purpose: Treatment
Keywords: Uganda, malaria, combination antimalarial therapy