Plain English Summary
Background and study aims.
This was the largest ever study in children hospitalized with severe malaria. It sought to determine whether a drug called artesunate was a better treatment than the usual drug quinine. Artesunate had been shown already to be superior in patients (mainly adults) studied in South-East Asia, but uncertainty remained over whether it was better in African children, who bear most of the burden of severe malaria in the world.
Who can participate?
The study was conducted in 11 centers located in 9 countries across Africa during the study period. All children hospitalized could be enrolled provided the doctor suspected severe malaria, their blood test showed malaria, they were over 18 months of age, and their parent or carer agreed.
What does the study involve?
The children were randomly allocated to receive one drug or the other by injection or by a drip. The medical staff were all aware of which treatment was given. The primary outcome of the study was whether or not the child survived to leave hospital. We also checked carefully for complications of the disease or the drug, particularly residual brain damage from cerebral malaria.
What are the possible benefits and risks of participating?
Quinine was the established time-honoured treatment. There were no risks to participating in the study and most children who were eligible were enrolled.
Where is the study run from?
The study was coordinated by the Mahidol Oxford Research Unit in Bangkok, Thailand
When is the study starting and how long is it expected to run for?
The study ran between Oct 3, 2005, and July 14, 2010
Who is funding the study?
The Wellcome Trust
Who is the main contact?
Prof NJ White
nickw@tropmedres.ac
Trial website
Contact information
Type
Scientific
Primary contact
Prof Nicholas J White
ORCID ID
Contact details
Faculty of Tropical Medicine
Wellcome Unit
420/6 Rajvithi Road
Bangkok
10400
Thailand
+66 (0)2 3549172
nickw@tropmedres.ac
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
076908
Study information
Scientific title
The AQUAMAT trial: An open label randomised comparison of injectable artesunate and quinine in children with severe falciparum malaria in Africa
Acronym
AQUAMAT
Study hypothesis
To compare the mortality and significant sequelae of severe falciparum malaria in African children treated with parenteral quinine, to those treated with parenteral artesunate.
Please note that as of 26/01/2009 this record has been extensively updated. All updates can be found in the relevant section under the above update date. Please also note that as of 26/01/2009 the trial dates have changed. The inital trial dates were as follows:
Initial anticipated start date: 18/07/2005
Initial anticipated end date: 31/12/2007 (amended to 30/04/2009 in February 2007)
As of 02/02/2010 the Democratic Republic of Congo was added as a country of recruitment.
As of 20/04/2010 this record was updated to include an extended anticipated end date ; the previous anticipated end date was 31/03/2010. At this time, the secondary endpoints were also updated; please see the relevant section for more details of this.
Ethics approval
1. UK: Oxford Tropical Medicine Research Ethics Committee (OXTREC) (UK), 11th August 2008 (ref: 03402)
2. The Gambia: The Gambia Government/MRC Laboratories Joint Ethics Committee, 5th October 2005 (ref: L2005.91)
3. Kenya: KEMRI National Ethics Review Committee, 21st October 2005 (ref: KEMRI/RES/7/3/1)
4. Ghana: University of Science and Technology School of Medical Science, Committee on Human Research Publication and Ethics, 23rd January 2006 (ref: CHRPE/01/06)
5. Mozambique: Ministry of Health, Comité Nacional de Bioética para a saùde, 4th June 2007 (ref: IRB 00002657-105/CNBS/07)
6. Tanzania: Ministry of Health, National Institute for Medical Research (NIMR), 20th April 2007 (ref: NIMR/HQ/R.8c/ Vol. 1/22)
7. Uganda: Mbarara University of Science and Technology, Institutional Ethical Review Committee, 22nd August 2007 (ref: Dos 1/6)
8. Nigeria: University of Ilorin Teaching Hospital, Ethical Review Committee, 26th October 2007 (ref: UITH/CAT/189/10/659)
9. Rwanda: Ministry of Health National Ethics Committee, 3rd April 2008 (ref: IRB 00001497 of IORG 0001100)
Added 02/02/2010:
10. Democratic Republic of Congo: Le Comité dEthique de lEcole de Santé Publique de lUniversité de Kinshasa approved on the 24th September 2009 (ref: 050/2009)
All other centres received ethics approval prior to recruiting the first participant.
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Malaria
Intervention
Please note that as of 01/09/10 this trial has reached its target sample size and recruitment has been closed. The trial is now in follow-up.
Current information as of 26/01/2009:
Patients are randomised to treatment with either intravenous (i.v.) or intramuscular (i.m.) artesunate or i.v. or i.m. quinine.
Initial information at time of registration:
In two of the study sites intramuscular artesunate will be compared with intramuscular quinine. In two other study sites the comparison will be between intravenous artesunate and intravenous quinine.
Intervention type
Drug
Phase
Not Applicable
Drug names
Artesunate and quinine
Primary outcome measure
In-hospital mortality
Secondary outcome measures
Current information as of 20/04/2010:
1. Neurological sequelae at day 28 after discharge from the hospital
2. Combined in-hospital mortality and neurological sequelae at day 28 after discharge from the hospital
Initial information at time of registration:
1. Neurological sequelae
2. Recovery times:
2.1. To localise pain
2.2. To speak
2.3. To sit unsupported
2.4. To eat or breast feed, and
2.5. To discharge from hospital
Assessed at discharge.
Overall trial start date
08/10/2005
Overall trial end date
31/12/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. OptiMal malaria rapid test positive, and
2. Treating physician considers patient to have severe malaria
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
5300
Participant exclusion criteria
1. Patient has received more than or equal to 24 hours of effective treatment with quinine or an artemisinin derivative, or
2. Patient has a known allergy to quinine or an artemisinin derivative
Recruitment start date
08/10/2005
Recruitment end date
31/12/2010
Locations
Countries of recruitment
Congo, Democratic Republic, Gambia, Ghana, Kenya, Mozambique, Nigeria, Rwanda, Tanzania, Uganda
Trial participating centre
Faculty of Tropical Medicine
Bangkok
10400
Thailand
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
The Wellcome Trust (UK) (grant ref: 076908)
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
Basic results (scientific)
Publication list
1. 2010 results of main AQUAMAT study in http://www.ncbi.nlm.nih.gov/pubmed/21062666
2. 2012 results of sub-study on malaria and HIV co-infection in Mozambique in http://www.ncbi.nlm.nih.gov/pubmed/22752514
3. 2012 substudy results plasma PfHRP2 in http://www.ncbi.nlm.nih.gov/pubmed/22927801
4. 2012 pharmacokinetics results in www.ncbi.nlm.nih.gov/pubmed/23183442
Publication citations
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Results of main AQUAMAT study
Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A, Chhaganlal KD, Bojang K, Olaosebikan R, Anunobi N, Maitland K, Kivaya E, Agbenyega T, Nguah SB, Evans J, Gesase S, Kahabuka C, Mtove G, Nadjm B, Deen J, Mwanga-Amumpaire J, Nansumba M, Karema C, Umulisa N, Uwimana A, Mokuolu OA, Adedoyin OT, Johnson WB, Tshefu AK, Onyamboko MA, Sakulthaew T, Ngum WP, Silamut K, Stepniewska K, Woodrow CJ, Bethell D, Wills B, Oneko M, Peto TE, von Seidlein L, Day NP, White NJ, , Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial., Lancet, 2010, 376, 9753, 1647-1657, doi: 10.1016/S0140-6736(10)61924-1.
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Pharmacokinetics results
Hendriksen IC, Maiga D, Lemnge MM, Mtove G, Gesase S, Reyburn H, Lindegardh N, Day NP, von Seidlein L, Dondorp AM, Tarning J, White NJ, Population pharmacokinetic and pharmacodynamic properties of intramuscular quinine in Tanzanian children with severe Falciparum malaria., Antimicrob. Agents Chemother., 2013, 57, 2, 775-783, doi: 10.1128/AAC.01349-12.
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Hendriksen IC, Ferro J, Montoya P, Chhaganlal KD, Seni A, Gomes E, Silamut K, Lee SJ, Lucas M, Chotivanich K, Fanello CI, Day NP, White NJ, von Seidlein L, Dondorp AM, Diagnosis, clinical presentation, and in-hospital mortality of severe malaria in HIV-coinfected children and adults in Mozambique., Clin. Infect. Dis., 2012, 55, 8, 1144-1153, doi: 10.1093/cid/cis590.
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Hendriksen IC, Mwanga-Amumpaire J, von Seidlein L, Mtove G, White LJ, Olaosebikan R, Lee SJ, Tshefu AK, Woodrow C, Amos B, Karema C, Saiwaew S, Maitland K, Gomes E, Pan-Ngum W, Gesase S, Silamut K, Reyburn H, Joseph S, Chotivanich K, Fanello CI, Day NP, White NJ, Dondorp AM, Diagnosing severe falciparum malaria in parasitaemic African children: a prospective evaluation of plasma PfHRP2 measurement., PLoS Med., 2012, 9, 8, e1001297, doi: 10.1371/journal.pmed.1001297.