Chloroquine Alone or in Combination for Malaria in Children in Malawi
Condition: Plasmodium Falciparum Infection
MeSH terms: Malaria
Intervention: Atovaquone-proguanil; Artesunate; Azithromycin; Chloroquine
Intervention description: 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
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 640.0
Sex: All
Minimum age: 6 Months
Maximum age: 5 Years
Healthy volunteers: No
Keywords: chloroquine, malaria, Plasmodium falciparum, Malawi, children

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects aged greater than or equal to 6 months to 5 years presenting to Ndirande
             Health Centre with signs or symptoms consistent with malaria including, but not
             limited to, one or more of the following:

               1. fever at the time of evaluation (axillary temperature greater than or equal to
                  37.5 degrees Celsius by digital thermometer)

               2. report of fever within the last two days

               3. clinically profound anemia (conjunctival or palmar pallor)

               4. headache

               5. body aches

               6. abdominal pain

               7. decreased intake of food or fluids

               8. weakness

          -  Weight greater than or equal to 5kg.

          -  Positive malaria smear for P. falciparum mono-infection with parasite density
             2,000-200,000/mm^3.

          -  Planning to remain in the study area for 1 year.

          -  Willingness to return for four-weekly routine visits, as well as unscheduled sick
             visits.

          -  Parental/guardian consent for each participant.

        Exclusion Criteria:

          -  Signs of severe malaria: One or more of the following:

               1. hemoglobin less than or equal to 5 g/dL

               2. prostration

               3. respiratory distress

               4. bleeding

               5. recent seizures, coma or obtundation (Blantyre coma score < 5)

               6. inability to drink

               7. persistent vomiting

          -  Known allergy or history of adverse reaction to chloroquine (CQ), artesunate,
             azithromycin, erythromycin or atovaquone-proguanil (AP)

          -  Chronic medication with any antibiotic or anti malarial medication

          -  Previous enrollment in this study

          -  Alanine aminotransferase (ALT) more than 5x the upper limit of normal or creatinine
             greater than 3x the upper limit of normal

          -  Evidence of chronic disease or physical stigmata of severe malnutrition (i.e., loss of
             muscle mass or subcutaneous tissue, edema, or skin or hair findings consistent with
             severe malnutrition)