Condition category
Infections and Infestations
Date applied
16/05/2005
Date assigned
10/06/2005
Last edited
09/08/2010
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Philip Rosenthal

ORCID ID

Contact details

San Francisco General Hopital
1001 Potrero Avenue
Building 30
Room 421
San Francisco
94110
United States of America
+1 415 206 8845
rosnthl@itsa.ucsf.edu

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

Study hypothesis

We will test the hypothesis that the malaria treatment incidence density (number of treatments for malaria per time at risk) will differ among patients randomised to our three treatment groups (amodiaquine and sulfadoxine-pyrimethamine versus amodiaquine and artesunate versus artemether-lumefantrine).

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Condition

Uncomplicated falciparum malaria

Intervention

Amodiaquine plus sulfadoxine-pyrimethamine versus amodiaquine plus artesunate versus artemether-lumefantrine

Intervention type

Drug

Phase

Not Specified

Drug names

Amodiaquine, sulfadoxine-pyrimethamine, artesunate, artemether-lumefantrine

Primary outcome measures

The effect of antimalarial drug therapy can be measured both in terms of drug efficacy (risk of true treatment failure) and post-treatment prophylactic effect (risk of new infection). To best reflect the overall impact of therapy, our primary outcome measurement will be the treatment incidence density (treatments per time at risk) for each treatment arm. To eliminate the period not influenced by study drugs, treatment count will exclude the first episode.

Follow-up time will be from the first episode to the end of the study. Treatment count will include both first-line treatments with study drugs and second-line treatments with quinine following study drug failure. It will be assumed that participants will not be at risk for repeat therapy for 14 days after treatment with quinine, for which resistance has not been reported, so this time will be excluded when calculating total time at risk.

Secondary outcome measures

1. Drug efficacy:
We will examine the efficacy of the different treatment groups using each episode of malaria treated with a study drug as the unit of analysis. We will examine the risk for repeat treatment as a function of time. Short-term (14-day) assessments of treatment efficacy will provide a standard analysis that will be useful for comparisons with other studies.
1.1. Specific short-term outcomes to be assessed will include:
1.1.1. Clinical and parasitological outcome
1.1.2. Rates of fever and parasite clearance
1.1.3. Change in hemoglobin level from day zero to 14
1.1.4. Presence of gametocytes following treatment
1.1.5. Safety and tolerability of study medications
1.2. Long-term (beyond 14-day) outcomes will be:
1.2.1. Risk of recrudescence
1.2.2. Risk of new infection using Kaplan-Meier product limit estimates of risk at various time intervals (i.e. four, six, and eight weeks after initiation of therapy)
In the analysis of long-term outcomes, molecular genotyping will be used to distinguish recrudescence (true treatment failure) from new infections.

2. Safety and tolerability:
All adverse events will be catalogued based on their frequency, severity, and relationship to study medication using standardised protocols. These indices of safety and tolerability among treatment groups will be compared using each episode of malaria treated with a study drug as the unit of analysis.

3. Other long-term outcomes that will be assessed will include:
3.1. Incidence of asymptomatic parasitemia
3.2. Change in haemoglobin level over time
3.3. Perceived tolerability of study medications among subjects and care givers
3.4. Drug costs (comparison of total cost per patient)

Overall trial start date

01/11/2004

Overall trial end date

20/04/2007

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged one to ten 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

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

601

Participant exclusion criteria

1. History (obtained from the parent/guardian) of any known serious chronic disease requiring frequent medical care (e.g. Acquired Immune Deficiency Syndrome [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 less than 10 kg
5. Severe malnutrition defined as weight-for-height or height-for-age Z-score less than -3
6. Homozygous haemoglobin SS (sickle cell) result by haemoglobin electrophoresis
7. Life-threatening screening laboratory value in the absence of malaria:
7.1. Absolute neutrophil count: less than 250/mm^3
7.2. Hemoglobin: less than 5.0 g/dl
7.3. Platelet count: less than 25,000/mm^3
7.4. Creatinine: less than two years: more than 1.5 mg/dl, more than two years: more than 2.0 mg/dl
7.5. Alanine transaminase (ALT): more than 15.0 x Upper Limit of Normal (ULN)
7.6. Bilirubin: more than 7.5 x ULN

Recruitment start date

01/11/2004

Recruitment end date

20/04/2007

Locations

Countries of recruitment

Uganda

Trial participating centre

San Francisco General Hopital
San Francisco
94110
United States of America

Sponsor information

Organisation

National Institutes of Health (NIH) - National Institute of Allergy and Infectious Diseases (NIAID) (USA)

Sponsor details

c/o Philip E. Coyne
Jr.
MD
MSPH
Program Officer
Parasitology and International Programs Branch
Division of Microbiology and Infectious Diseases
NIAID
6610 Rockledge Dr.
Room 5093
MSC 6604
Bethesda
20892-6603
United States of America

Sponsor type

Government

Website

Funders

Funder type

Government

Funder name

The National Institute of Allergy and Infectious Diseases (NIAID) (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17519410
2. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20689585

Publication citations

  1. Results

    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, 297, 20, 2210-2219, doi: 10.1001/jama.297.20.2210.

  2. Results

    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, 5, 7, e11759, doi: 10.1371/journal.pone.0011759.

Additional files

Editorial Notes