NCT00123552

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
601

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Nov 2004

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2004

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

July 22, 2005

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 25, 2005

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2006

Completed
2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2008

Completed
Last Updated

June 9, 2020

Status Verified

June 1, 2020

Enrollment Period

1.6 years

First QC Date

July 22, 2005

Last Update Submit

June 3, 2020

Conditions

Malaria

Keywords

Uganda, malaria, combination antimalarial therapy

Outcome Measures

Primary Outcomes (1)

  • Annual incidence of malaria per treatment arm

    duration of study

Secondary Outcomes (5)

  • Short term: clinical and parasitological outcome; rates of fever and parasite clearance; presence of gametocytes following treatment

    14 days

  • Short term: change in hemoglobin level from day 0-14; safety and tolerability of study medications

    14 days

  • Long term: risk of reinfection using Kaplan-Meier product limit estimates of risk at various time intervals

    Beyond 14 days to end of study

  • Long term: risk of recrudescence; change in hemoglobin level; safety and tolerability of study medications

    Beyond 14 days to end of study

  • Longitudinal: prevalence of asymptomatic parasitemia; mean hemoglobin

    4 years

Study Arms (3)

1

EXPERIMENTAL
Drug: Amodiaquine+Artesunate

2

EXPERIMENTAL
Drug: Amodiaquine+Sulfadoxine/Pyrimethamine

3

EXPERIMENTAL
Drug: Artemether+Lumefantrine

Interventions

Amodiaquine+ArtesunateDRUG

Amodiaquine 10 mg/kg on day 1, then 5 mg/kg on day 2 and 3; Artesunate 4 mg/kg/d for three days

1
Amodiaquine+Sulfadoxine/PyrimethamineDRUG

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

2
Artemether+LumefantrineDRUG

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

3

Eligibility Criteria

Age1 Year - 10 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Phase I
  • Age 1 to 10 years.
  • Agreement to come to the study clinic for any febrile episode or other illness.
  • Agreement to avoid medications administered outside the study.
  • Willingness of parents or guardians to provide informed consent.
  • Phase II
  • Child and Guardian/Parent belong to household currently enrolled in the study.
  • Age 1 to 10 years.
  • Agreement to come to the study clinic for any febrile episode or other illness.
  • Agreement to avoid medications administered outside the study.
  • Willingness of parents or guardians to provide informed consent.

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Assessment Center - Mulago Hospital

Kampala, Uganda

Location

Related Publications (8)

  • Davis JC, Clark TD, Kemble SK, Talemwa N, Njama-Meya D, Staedke SG, Dorsey G. Longitudinal study of urban malaria in a cohort of Ugandan children: description of study site, census and recruitment. Malar J. 2006 Mar 21;5:18. doi: 10.1186/1475-2875-5-18.

    PMID: 16551365RESULT

  • Njama-Meya D, Clark TD, Nzarubara B, Staedke S, Kamya MR, Dorsey G. Treatment of malaria restricted to laboratory-confirmed cases: a prospective cohort study in Ugandan children. Malar J. 2007 Jan 21;6:7. doi: 10.1186/1475-2875-6-7.

    PMID: 17239256RESULT

  • Dorsey G, Staedke S, Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Dokomajilar C, Kamya MR, Rosenthal PJ. Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. JAMA. 2007 May 23;297(20):2210-9. doi: 10.1001/jama.297.20.2210.

    PMID: 17519410RESULT

  • Clark TD, Greenhouse B, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Staedke SG, Seto E, Kamya MR, Rosenthal PJ, Dorsey G. Factors determining the heterogeneity of malaria incidence in children in Kampala, Uganda. J Infect Dis. 2008 Aug 1;198(3):393-400. doi: 10.1086/589778.

    PMID: 18522503RESULT

  • Maiteki-Sebuguzi C, Jagannathan P, Yau VM, Clark TD, Njama-Meya D, Nzarubara B, Talisuna AO, Kamya MR, Rosenthal PJ, Dorsey G, Staedke SG. Safety and tolerability of combination antimalarial therapies for uncomplicated falciparum malaria in Ugandan children. Malar J. 2008 Jun 11;7:106. doi: 10.1186/1475-2875-7-106.

    PMID: 18547415RESULT

  • Staedke SG, Jagannathan P, Yeka A, Bukirwa H, Banek K, Maiteki-Sebuguzi C, Clark TD, Nzarubara B, Njama-Meya D, Mpimbaza A, Rosenthal PJ, Kamya MR, Wabwire-Mangen F, Dorsey G, Talisuna AO. Monitoring antimalarial safety and tolerability in clinical trials: a case study from Uganda. Malar J. 2008 Jun 11;7:107. doi: 10.1186/1475-2875-7-107.

    PMID: 18547416RESULT

  • Greenhouse B, Slater M, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Clark TD, Staedke SG, Kamya MR, Hubbard A, Rosenthal PJ, Dorsey G. Decreasing efficacy of antimalarial combination therapy in Uganda is explained by decreasing host immunity rather than increasing drug resistance. J Infect Dis. 2009 Mar 1;199(5):758-65. doi: 10.1086/596741.

    PMID: 19199542RESULT

  • Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Greenhouse B, Staedke SG, Kamya MR, Dorsey G, Rosenthal PJ. Incidence of malaria and efficacy of combination antimalarial therapies over 4 years in an urban cohort of Ugandan children. PLoS One. 2010 Jul 30;5(7):e11759. doi: 10.1371/journal.pone.0011759.

    PMID: 20689585RESULT

MeSH Terms

Conditions

Malaria

Interventions

amodiaquine, artesunate drug combinationPyrimethamineArtemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

PyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsArtemetherArtemisininsReactive Oxygen SpeciesFree RadicalsInorganic ChemicalsOrganic ChemicalsLumefantrineFluorenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSesquiterpenesTerpenesPolycyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
CARE PROVIDER
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

July 22, 2005

First Posted

July 25, 2005

Study Start

November 1, 2004

Primary Completion

June 1, 2006

Study Completion

December 1, 2008

Last Updated

June 9, 2020

Record last verified: 2020-06

Locations

UG(1)