This study will be a clinical trial comparing different ways to treat uncomplicated malaria in a group of Ugandan children. Participants will be assigned to interventional groups by chance. Participants will also be unaware of the intervention assignment; investigators will be aware.

Condition	Intervention	Phase
Malaria	Drug: Amodiaquine+Artesunate  Drug: Amodiaquine+Sulfadoxine/Pyrimethamine  Drug: Artemether+Lumefantrine	Phase IV

Further Study Details: 

Expected Total Enrollment:  600

Malaria is one of the most important infectious diseases, and its control is greatly threatened by drug resistance. Current methods for evaluating drug efficacy, including assessing outcome 14 days after treating a single malaria episode, likely significantly underestimate the level of drug resistance. This will be a randomized, single-blinded, longitudinal clinical trial comparing the safety, tolerability, and efficacy of three different combination antimalarial regimens for the treatment of uncomplicated malaria. The clinical study will recruit participants form a defined and mapped source population in the Mulago III Parish within the Kawempe District in Ugandan, conduct a survey of epidemiological factors on each study participant, and follow clinical care and outcomes for this cohort 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. Probability sampling of a census of households within a geographically defined community will be used to select a random sample of 600 Ugandan children between the ages of 1 to 10 years. Participants will be followed for 3 years for all routine medical care in our study clinic at Mulago Hospital. All patients presenting to our 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. All subsequent episodes of uncomplicated malaria will be treated with each participant''''s assigned treatment regiment. All 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. All episodes diagnosed more than 14 days after a previous episode will be considered new episodes for treatment purposes. Study investigators involved in patient evaluation and treatment outcomes classification will be blinded to treatment assignment. Study subjects will not be informed of their treatment assignments. Dosing regimens will be the same for all treatment groups, including the use of placebo tablets where applicable. The taste and color of study medications will not be identical. Only nurses responsible for administration of study drugs will remain unblinded to participant''''s assigned treatment regimens. Routine home visits will be made for any participant not seen in our study clinic after any consecutive 30-day period. Routine home visits will include review of study protocol with study participants, assessment for any outside medical care, a focused history and physical examination and routine laboratory testing. There is no direct benefit to the children participating in this trial. From studying the children''''s samples we may learn more about malaria or other diseases: how to prevent them, how to treat them, how to cure them. We hypothesize that longitudinal evaluation will identify important differences between the efficacies and selective pressures of leading antimalarial combination therapies even if short-term activities are similar. We further hypothesize that identifiable parasite and host polymorphisms will help predict outcomes after antimalarial therapy and that the characterization of these polymorphisms will identify factors that contribute to malaria incidence and responses to therapy.

Ages Eligible for Study:  1 Year   -   10 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

1. Age 1 to 10 years. 2. Agreement to come to the study clinic for any febrile episode or other illness. 3. Agreement to avoid medications administered outside the study. 4. Willingness of parents or guardians to provide informed consent.

Exclusion Criteria:

1. History (obtained from the parent/guardian) of any known serious chronic disease requiring frequent medical care (e.g. AIDS, sickle cell disease, malignancy). 2. Intention to move from Kampala during the follow-up period. 3. History (obtained from the parent/guardian) of serious side effects to study medications or sulfa drugs. 4. Weight < 10 kg. 5. Severe malnutrition defined as weight-for-height or height-for-age Z-score < -3. 6. Homozygous hemoglobin SS (sickle cell) result by hemoglobin electrophoresis. 7. Life-threatening screening laboratory value in the absence of malaria: a) Absolute neutrophil count: < 250/mm� b) Hemoglobin: < 5.0 g/dL c) Platelet count: < 25,000/mm� d) Creatinine: < 2 years: > 1.5 mg/dL, >= 2 years: > 2.0 mg/dL e) ALT: > 15.0 x ULN f) Bilirubin: > 7.5 x ULN

Please refer to this study by ClinicalTrials.gov identifier  NCT00123552

Philip Rosenthal      (415) 206-8845    rosnthl@itsa.ucsf.edu

Uganda
      University Of California San Francisco, Kampala,  Uganda; Recruiting
      Assessment Center- Mulago Hospital, Kampala,  Uganda; Recruiting

Study ID Numbers:  04-068
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 22, 2005
ClinicalTrials.gov Identifier:  NCT00123552
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-07-26