Chloroquine Alone or in Combination for Malaria in Children in Malawi
Condition: Plasmodium Falciparum Infection
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 3

Summary: 
      Malaria is a sickness caused by a germ that can get into a person's body when a mosquito
      bites them. It can cause fever, headache, body aches and weakness. It can even cause death,
      especially in children. When malaria is treated with the appropriate medicine(s), it can be
      cured completely. The purpose of this study is to find out if it is better to use chloroquine
      alone or in combination with another drug to most effectively treat malaria. About 640
      children with malaria, aged 6 months to 5 years of age, from the Blantyre Malaria Project
      Research Clinic at the Ndirande Health Center in Malawi will be in the study. They will be
      treated with either chloroquine alone or a combination of chloroquine plus another medication
      (azithromycin or artesunate or atovaquone-proguanil) every time they get malaria for a year.
      Blood samples will be collected and tested at least every 4 weeks. Participants will be
      involved in the study for 1 year.
    

Detailed description: 
      Combination therapy is becoming the mainstay of malaria treatment. In general, the goal of
      combination therapy is to treat resistant infections successfully and to prevent the
      emergence and spread of resistance. The antimalarial combination therapies currently in use
      were not designed based on optimal pairing of drugs to deter the development and spread of
      parasite resistance to the individual partner drugs in settings of high malaria transmission.
      Careful studies are needed to identify the pharmacokinetic and pharmacodynamic properties of
      drug combinations that will deter resistance and prolong the useful therapeutic life of the
      next generation of antimalarial drug combinations. Current in vivo methods for measuring
      antimalarial drug efficacy in high-transmission areas use a 14 or 28-day follow-up period,
      but a single episode study misses several critical factors in assessing the efficacy and
      impact of antimalarial treatment. When follow-up is extended beyond 28 days, more cases of
      apparent resistance or treatment failure are found. Single-episode studies cannot assess the
      impact of therapy on the incidence of malaria over time. These limitations of standard in
      vivo studies have led the investigators to advocate longitudinal studies of drug efficacy. In
      addition to measuring efficacy of individual treatments, longitudinal studies measure
      sustained efficacy with repeated use of the same regimen over time, a scenario that more
      accurately reflects the real-life use of anti-malarial medication. The primary outcome of
      interest is the incidence of malaria episodes, as well as the secondary outcomes of anemia
      and severe malaria, are all highly relevant to public health policy-makers, as they reflect
      not only the burden of disease but also the utilization of health resources. Longitudinal
      studies also permit assessment of how pharmacokinetic properties of drugs affect the
      incidence of treatment episodes. This is a randomized, open-label, longitudinal drug efficacy
      trial. Participants will include 640 children, aged 6 months to 5 years, who are found to
      have uncomplicated malaria at the Blantyre Malaria Project Research Clinic at the Ndirande
      Health Centre in Blantyre, Malawi. After enrollment, participants will be randomized to one
      of four treatment arms: chloroquine alone or chloroquine in combination with artesunate,
      atovaquone-proguanil (AP), or azithromycin. The treatment outcome will be assessed through a
      standard 28-day efficacy study. Participants will subsequently be evaluated every 4 weeks and
      encouraged to return to the study clinic any time they are ill during the course of one year.
      If a new episode of uncomplicated malaria is diagnosed, the participant will receive the same
      therapy as assigned on enrollment. Polymerase chain reaction-corrected 28-day efficacy will
      be evaluated for each treatment episode. The primary study objective is to compare annual
      incidence of malaria clinical episodes. Secondary objectives are to: assess anti-malarial
      drug efficacy at first administration, by treatment arm; assess anti-malarial drug efficacy
      during subsequent episodes of malaria, by treatment arm; measure prevalence of chloroquine
      resistant parasites during the trial, by treatment arm; assess effect of each treatment arm
      on anemia at the end of study participation; assess safety of these drugs with repeated use;
      determine the chloroquine blood levels at which chloroquine sensitive and resistant parasites
      are able to cause infection; assess the effect of population movements on the risk of malaria
      infection; and assess the spatial patterns and the environmental determinants of malaria
      infection. Participants will be involved in study rela
    

Intervention name(s): Atovaquone-proguanil; Artesunate; Azithromycin; Chloroquine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Atovaquone-proguanil: once a day for 3 days, Pediatric tablet: 62.5 mg/25 mg, Full strength tablet: 250 mg/100 mg; Artesunate: 4mg/kg once a day for 3 days, 50 mg tablet; Azithromycin 30 mg/kg once a day for 3 days, 200 mg/5cc suspension; Chloroquine: 10 mg/kg on days 0 and 1, 5 mg/kg/day on day 2, 100 mg tablet.
Intervention MeSH terms: Azithromycin; Artesunate; Chloroquine; Atovaquone; Proguanil; Atovaquone, proguanil drug combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: chloroquine, malaria, Plasmodium falciparum, Malawi, children