To assess the efficacy and tolerability of three antimalarial treatments in The Democratic Republic of Congo (DRC)

ISRCTN ISRCTN20984426
DOI https://doi.org/10.1186/ISRCTN20984426
Secondary identifying numbers Version # 1.01 30 March 2011
Submission date
22/09/2011
Registration date
06/10/2011
Last edited
10/02/2016
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Malaria is a serious tropical disease spread by mosquitoes. Antimalarial medication is used to prevent and treat malaria, with the first-line treatment being the first treatment given. We are carrying out a detailed assessment of the effectiveness of the current first-line antimalarial treatment, 5 years after its introduction. We will also assess the effectiveness of two other antimalarial treatments which could replace the first line in the near future, or be proposed as first-line treatment as part of a multiple first-line treatment strategy.

Who can participate?
Children aged 6 to 59 months with uncomplicated malaria

What does the study involve?
Participants are randomly allocated to one of the three treatments. The three treatments are amodiaquine-artesunate, dihydroartemisinin-piperaquine and artemether-lumefantrine. The study is open label, so the doctor and the patients both know which treatment they have been assigned to. All children are hospitalized for four days and given supervised treatment. The effectiveness of the treatment is measured and participants are followed up for 42 days after treatment.

What are the possible benefits and risks of participating?
The results of the study will enable the Ministry of Health to make informed decisions about whether the current national antimalarial treatment guidelines should be updated, and offer possible alternatives.

Where is the study run from?
The study will be conducted in Kinshasa, Democratic Republic of Congo.

When is the study starting and how long is it expected to run for?
September 2011 to December 2012

Who is funding the study?
Oxford University (UK)

Who is the main contact?
Prof Nick PJ Day

Contact information

Prof Nick PJ Day
Scientific

Faculty of Tropical Medicine
Mahidol University
3rd Floor
60th Anniversary Chalermprakiat Building
420/6 Rajwithi Road
Bangkok
10400
Thailand

Study information

Study designRandomised three-arm open study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleA randomised study to assess the efficacy and tolerability of three Artemisinin-based combination therapy (ACT) in The Democratic Republic of Congo (DRC)
Study objectivesThis study will assess the efficacy of amodiaquine-artesunate for the treatment of uncomplicated P. falciparum malaria in children in Kinshasa, DRC, five years after its introduction as a first line treatment, and compare this with the efficacies of dihydroartemisinin-piperaquine and artemether-lumefantrine.
Ethics approval(s)1. Oxford Tropical Research Ethics Committee (OXTREC), 06/04/2011
2. Ethics Committee of Kinshasa University, Ministry of Higher Education and University, Democratic Republic of Congo (Ministère de I'Enseignement Supérieur et Universitaire, République Démocratique du Congo), 21/04/2011
Health condition(s) or problem(s) studiedMalaria
InterventionThis is a randomised, open study, comparing three ACTs, dihydroartemisinin-piperaquine (DHA-PQ), artemether–lumefantrine (ALN) and amodiaquine-artesunate coformulated (AQ-AS), for the treatment of symptomatic uncomplicated falciparum malaria. The study is post-marketing, all three study drugs are in fact commercialized and used worldwide. Our aim is to monitor their efficacy and tolerability in this particular geographical area. Dosage and length of treatment are according to manufacturer. Children aged 6 to 59 months with uncomplicated P. falciparum malaria are randomly assigned to one of the three arms. All children are hospitalized for 3 days and given supervised treatment. Treatment efficacy is measured according to WHO (Methods for surveillance of antimalarial drug, WHO 2009). Patients are followed-up actively weekly for 42 days after treatment. Treatment allocation is concealed until recruitment is confirmed and the laboratory technicians reading all malaria smears have no knowledge of the treatment received by individual patients. Randomisation is in blocks of 15.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Amodiaquine-artesunate, dihydroartemisinin-piperaquine, artemether-lumefantrine
Primary outcome measure1. Clinical and parasitological cure by day 42 post-treatment
2. Treatment tolerability
Secondary outcome measures1. The median parasite clearance time (PCT)
3. Fever clearance time (FCT)
Overall study start date08/09/2011
Completion date31/12/2012

Eligibility

Participant type(s)Patient
Age groupNeonate
SexBoth
Target number of participants684
Key inclusion criteria1. Children aged 3 to 59 months
2. Weight ≥ 5 kg [the minimum weight for treatment with artemether-lumefantrine (ALN)]
3. Mono-infection with P. falciparum
4. Parasitaemia of ≥2,000 and ≤200,000 asexual parasites per µL
5. Axillary temperature 37.5 °C or history of fever in the preceding 24 hrs
6. Ability to swallow oral medication
7. Haemoglobin ≥5.0 g/dL
8. Parents/guardians agree to hospitalize the child for the length of treatment (34 days) and bring the patient for planned follow-up visits at day 7, 14, 21, 28, 35, 42
9. Signed consent from guardian / parents
Key exclusion criteria1. Danger signs of severe malaria or signs of severe malaria (WHO 2000)
2. Children with severe malnutrition, marasmus or oedematous malnutrition (WHO 2006)
3. Febrile condition due to diseases other than malaria [e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal or hepatic diseases, human immunodeficiency virus (HIV) / acquired immune deficiency syndrome (AIDS)]
4. History of hypersensitivity reactions or contraindication to any medicine being tested
5. A clear history of adequate antimalarial treatment in the preceding 72 hours with drugs expected to be effective
6. Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocisti carini pneumonia in children born to HIV positive women
Date of first enrolment08/09/2011
Date of final enrolment31/12/2012

Locations

Countries of recruitment

  • Congo, Democratic Republic
  • Thailand

Study participating centre

Mahidol University
Bangkok
10400
Thailand

Sponsor information

The Centre for Tropical Medicine (UK)
University/education

CCVTM
Churchill Hospital
University of Oxford
Oxford
OX3 7LJ
England
United Kingdom

Email nickd@tropmedres.ac
Website http://www.tropmedres.ac/
ROR logo "ROR" https://ror.org/052gg0110

Funders

Funder type

University/education

Oxford University (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/09/2014 Yes No

Editorial Notes

10/02/2016: Plain English summary added

On 13/12/2012 the overall trial end date was changed from 08/09/2012 to 31/12/2012.