Condition category
Infections and Infestations
Date applied
22/09/2011
Date assigned
06/10/2011
Last edited
10/02/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Prof Nick PJ Day

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Version # 1.01 30 March 2011

Study information

Scientific title

A randomised study to assess the efficacy and tolerability of three Artemisinin-based combination therapy (ACT) in The Democratic Republic of Congo (DRC)

Acronym

Study hypothesis

This 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

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

Study design

Randomised three-arm open study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

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

This 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 type

Drug

Phase

Not Applicable

Drug names

Amodiaquine-artesunate, dihydroartemisinin-piperaquine, artemether-lumefantrine

Primary outcome measures

1. Clinical and parasitological cure by day 42 post-treatment
2. Treatment tolerability

Secondary outcome measures

1. The median parasite clearance time (PCT)
3. Fever clearance time (FCT)

Overall trial start date

08/09/2011

Overall trial end date

31/12/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. 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

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

684

Participant exclusion criteria

1. 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

Recruitment start date

08/09/2011

Recruitment end date

31/12/2012

Locations

Countries of recruitment

Congo, Democratic Republic

Trial participating centre

Mahidol University
Bangkok
10400
Thailand

Sponsor information

Organisation

The Centre for Tropical Medicine (UK)

Sponsor details

CCVTM
Churchill Hospital
University of Oxford
Oxford
OX3 7LJ
United Kingdom
-
nickd@tropmedres.ac

Sponsor type

University/education

Website

http://www.tropmedres.ac/

Funders

Funder type

University/education

Funder name

Oxford University (UK)

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

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25001306

Publication citations

  1. Results

    Onyamboko MA, Fanello CI, Wongsaen K, Tarning J, Cheah PY, Tshefu KA, Dondorp AM, Nosten F, White NJ, Day NP, Randomized Comparison of the Efficacies and Tolerabilities of Three Artemisinin-Based Combination Treatments for Children with Acute Plasmodium falciparum Malaria in the Democratic Republic of the Congo., Antimicrob. Agents Chemother., 2014, 58, 9, 5528-5536, doi: 10.1128/AAC.02682-14.

Additional files

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.