Phase 3
N=640
Chloroquine Alone or in Combination for Malaria in Children in Malawi
Plasmodium Falciparum Infection
Bottom Line
View on ClinicalTrials.gov: NCT00379821 ↗Enrolled (actual)
640
Serious AEs
7.7%
Results posted
Jul 2011
Primary outcome: Primary: Number of Clinical Malaria Episodes Per Year of Follow-up — 0.61; 0.68; 0.64; 0.59 Episodes per PYAR — p=0.8097
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Atovaquone-proguanil (Drug); Artesunate (Drug); Azithromycin (Drug); Chloroquine (Drug)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary completion
- Aug 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Clinical Malaria Episodes Per Year of Follow-up |
0.61; 0.68; 0.64; 0.59 | 0.8097 |
| SECONDARY Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm |
2; 1 | — |
| SECONDARY Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm |
2; 1 | — |
| SECONDARY Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm |
2; 1 | — |
| SECONDARY Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm |
2; 1 | — |
| SECONDARY Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm |
2; 1 | — |
| SECONDARY Number of Cases of Severe Malaria in Each Treatment Arm |
0; 2; 2; 6 | — |
| SECONDARY Mean Hemoglobin at the Last Study Visit in Each Treatment Arm for the Age Group of Participants 3 Years of Age or Younger. |
11.6; 11.7; 12.2; 11.8 | — |
| SECONDARY Mean Hemoglobin at the Last Study Visit in Each Treatment Arm for the Age Group of Participants Greater Than 3 Years to 5 Years of Age. |
12.5; 12.3; 12.1; 12.5 | — |
| SECONDARY Mean Creatinine in Each Treatment Arm (Renal Function) |
44.2 | — |
| SECONDARY Mean Creatinine in Each Treatment Arm (Renal Function) |
44.2 | — |
| SECONDARY Mean Creatinine in Each Treatment Arm (Renal Function) |
44.2 | — |
| SECONDARY Mean Creatinine in Each Treatment Arm (Renal Function) |
44.2 | — |
| SECONDARY Mean Creatinine in Each Treatment Arm (Renal Function) |
44.2 | — |
| SECONDARY Mean Creatinine in Each Treatment Arm (Renal Function) |
44.2 | — |
| SECONDARY Mean Creatinine in Each Treatment Arm (Renal Function) |
44.2 | — |
| SECONDARY Mean Creatinine in Each Treatment Arm (Renal Function) |
44.2 | — |
| SECONDARY Mean Creatinine in Each Treatment Arm (Renal Function) |
44.2 | — |
| SECONDARY Mean Creatinine in Each Treatment Arm (Renal Function) |
44.2 | — |
| SECONDARY Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function) |
13.9 | — |
| SECONDARY Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function) |
13.9 | — |
| SECONDARY Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function) |
13.9 | — |
| SECONDARY Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function) |
13.9 | — |
| SECONDARY Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function) |
13.9 | — |
| SECONDARY Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function) |
13.9 | — |
| SECONDARY Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function) |
13.9 | — |
| SECONDARY Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function) |
13.9 | — |
| SECONDARY Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function) |
13.9 | — |
| SECONDARY Mean Alanine Transaminase (ALT) in Each Treatment Arm (Hepatic Function) |
13.9 | — |
| SECONDARY Number of Participants in Each Treatment Arm Who Change From "Normal" to "Abnormal" on Any Questions of the Neurological Examination |
6; 4; 3; 12 | — |
| SECONDARY Number of Participants Infected With Parasites With the Mutation Pfcrt 76T on Day 0 of the Initial Episode of Malaria |
1; 0; 0; 0 | — |
| SECONDARY Number of Participants Infected With Parasites With the Mutation Pfcrt 76T at Recrudescent Episodes of Malaria |
0; 0; 1; 0 | — |
| SECONDARY Number of Participants With New and Recrudescent Malaria Infections After Initial Treatment |
0; 0; 1; 0; 1; 0 | — |
| SECONDARY Number of Participants With New and Recrudescent Infections After Subsequent New Episodes |
0; 0; 1; 1; 0; 0 | — |
| SECONDARY Time to First Malaria Episode in Participants Who Travelled and Slept Outside the City Versus Those Who Did Not Travel and Sleep Outside the City. |
432; 201; 0; 0; 63; 28 | 0.79 |
| SECONDARY Nearest Neighbor Index as a Measure of Spatial Pattern of the Distribution of Malaria Cases in Ndirande |
0.328 | — |
| SECONDARY Pharmacokinetics of Chloroquine Represented by Time of Maximal Concentration (Tmax) and Chloroquine Half-life |
5.6; 5.6; 5.5; 5.6; 41.6; 46.2 | — |
| SECONDARY Pharmacokinetics of Chloroquine Represented by Maximum Concentration (Cmax) |
351.0; 345.1; 353.1; 384.2 | — |
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:
- fever at the time of evaluation (axillary temperature greater than or equal to 37.5 degrees Celsius by digital thermometer)
- report of fever within the last two days
- clinically profound anemia (conjunctival or palmar pallor)
- headache
- body aches
- abdominal pain
- decreased intake of food or fluids
- 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:
- hemoglobin less than or equal to 5 g/dL
- prostration
- respiratory distress
- bleeding
- recent seizures, coma or obtundation (Blantyre coma score < 5)
- inability to drink
- 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)
Data sourced from ClinicalTrials.gov (NCT00379821). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.