Condition category
Infections and Infestations
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Background and study aims
Malaria is a serious tropical disease caused by a parasite spread by mosquitoes. Malaria has become increasingly difficult to treat over the last 50 years. The reason is that the parasite is able to adapt and become resistant to antimalarial drugs. In response to this problem the approach to treating malaria has changed. Combinations of drugs are used to reduce the chance of resistance developing. At first malaria patients were given the different treatments as separate tablets. This meant there was still a chance that patients might take one of the treatments without the other, especially if one had more side-effects. Increasingly more combined treatments have been developed with both drugs present in a single tablet. The aim of this study is to compare a new combined tablet containing two antimalarial drugs (artesunate and mefloquine) with the same drugs given as loose tablets for the treatment of malaria.

Who can participate?
Adults and children with malaria

What does the study involve?
Participants are randomly allocated to receive either received the new combined tablet or the separate tablets for 3 days as treatment for their malaria. Participants are seen daily for 3 days when they are given the treatment under supervision and then weekly for 9 weeks when blood samples are taken to see if they have been cured of their malaria.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Clinics of the Shoklo Malaria Research Unit (Thailand)

When is the study starting and how long is it expected to run for?
July 2004 to October 2005

Who is funding the study?
1. Wellcome Trust (UK)
2. Drugs for Neglected Disease Initiative (Switzerland)
3. European Commission (Belgium)

Who is the main contact?
Prof. Nicholas J White

Trial website

Contact information



Primary contact

Prof Nicholas J White


Contact details

Wellcome Unit
Faculty of Tropical Medicine
420/6 Rajvithi Road
+66 (0)2 3549172

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

A randomised, open study to assess the safety and efficacy of a new artesunate-mefloquine coformulation with an equivalent dose regimen of the individual drugs for the treatment of acute uncomplicated falciparum malaria (Thailand)


Study hypothesis

The aim of this trial is to measure the efficacy of a new fixed dose combination of mefloquine and artesunate for the treatment of acute uncomplicated malaria in adults and children and compare this to the efficacy of the loose tablets. The tolerability and safety of the new treatment will also be assessed and pharmacokinetic data will be collected.

Ethics approval

Institutional Review Boards of:
1. Faculty of Tropical Medicine, Mahidol University, Thailand, 20/02/2004
2. Oxford Tropical Research Ethics Committee (OXTREC), Oxford University, UK, 04/08/2004
3. Secretariat Committee on Research Involving Human Subjects (SCRIHS), World Health Organization (WHO), July 2004

Study design

Randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use contact details to request a participant information sheet




Fixed dose coformulation (intervention):
Once a day for three days - target dose of mefloquine is 8 mg/kg/day and for artesunate is 4 mg/kg/day using paediatric tablets 25/50 mg artesunate/mefloquine, or adult tablets 100/200 mg artesunate/mefloquine.

Non fixed tablets/standard dose (control):
Artesunate 12 mg/kg split as 4 mg/kg/day for three days and mefloquine 25 mg/kg split as 15 mg/kg/day and 10 mg/kg/day on second and third days of treatment.

Intervention type



Not Applicable

Drug names


Primary outcome measure

1. Parasitological cure
2. Adverse effects

Secondary outcome measures

1. Tolerability and safety of drugs defined as incidence of adverse events within 28 days of follow up
2. Haematological recovery during 63 days of follow up
3. Incidence of Plasmodium vivax infection during 63 days of follow up
4. Prevalence of gametocytaemia during 63 days of follow up
5. Description of population pharmacokinetic profile of mefloquine and artesunate during 63 days of follow up

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Age more than six months, either sex
2. Minimum weight of 5 kg
3. Microscopically confirmed mono or mixed infection of P. falciparum (asexual falciparum parasitaemia more than 5/500 White Blood Cell [WBC] count)
4. History of fever or presence of fever (tympanic or axillary temperature more than 37.5°C)
5. Written informed consent to participate in trial

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Pregnancy or lactation
2. P. falciparum asexual stage parasitaemia more than 4% red blood cells (175,000/µL)
3. Clinical features of severe malaria: impaired consciousness, inability to drink or breast feed, convulsions during the present illness, prostration, severe anaemia, respiratory distress, shock, spontaneous bleeding, acute haemolysis with haemoglobinuria
4. Other significant illnesses or signs e.g. severe jaundice, liver disease, renal disease, severe malnutrition
5. Recent ingestion of mefloquine within previous 60 days
6. Contraindications to mefloquine - history of convulsions and/or neuropsychiatric illnesses
7. Known hypersensitivity to artemisinins or mefloquine
8. Splenectomy

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Faculty of Tropical Medicine

Sponsor information


Drugs for Neglected Diseases initiative (DNDi) (Switzerland)

Sponsor details

15 Chemin Louis Dunant
+41 (0)22 906 9230

Sponsor type

Research organisation



Funder type


Funder name

Wellcome Trust

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

International organizations


United Kingdom

Funder name

Drugs for Neglected Diseases initiative (DNDi) (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

European Commission (Belgium) (INCO-Dev programme) (project number: ICA4-2001 10193)

Alternative name(s)

European Union, EC, EU

Funding Body Type

government organisation

Funding Body Subtype

National government


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

2006 results in

Publication citations

  1. Results

    Ashley EA, Lwin KM, McGready R, Simon WH, Phaiphun L, Proux S, Wangseang N, Taylor W, Stepniewska K, Nawamaneerat W, Thwai KL, Barends M, Leowattana W, Olliaro P, Singhasivanon P, White NJ, Nosten F, An open label randomized comparison of mefloquine-artesunate as separate tablets vs. a new co-formulated combination for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand., Trop. Med. Int. Health, 2006, 11, 11, 1653-1660, doi: 10.1111/j.1365-3156.2006.01724.x.

Additional files

Editorial Notes

28/03/2017: Internal review. 20/10/2016: Plain English summary added.