Condition category
Infections and Infestations
Date applied
15/04/2005
Date assigned
07/06/2005
Last edited
20/10/2016
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 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
nickw@tropmedres.ac

Trial website

Contact information

Type

Scientific

Primary contact

Prof Nicholas J White

ORCID ID

Contact details

Wellcome Unit
Faculty of Tropical Medicine
420/6 Rajvithi Road
Bangkok
10400
Thailand
+66 (0)2 3549172
nickw@tropmedres.ac

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RPC084

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)

Acronym

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

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

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

Condition

Malaria

Intervention

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

Drug

Phase

Not Applicable

Drug names

Artesunate-mefloquine

Primary outcome measures

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

28/07/2004

Overall trial end date

01/10/2005

Reason abandoned

Eligibility

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

Patient

Age group

Mixed

Gender

Both

Target number of participants

500

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

28/07/2004

Recruitment end date

01/08/2005

Locations

Countries of recruitment

Thailand

Trial participating centre

Faculty of Tropical Medicine
Bangkok
10400
Thailand

Sponsor information

Organisation

Drugs for Neglected Diseases initiative (DNDi) (Switzerland)

Sponsor details

15 Chemin Louis Dunant
Geneva
CH-1202
Switzerland
+41 (0)22 906 9230
dndi@dndi.org

Sponsor type

Research organisation

Website

http://www.dndi.org

Funders

Funder type

Charity

Funder name

Wellcome Trust

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Funder name

Drugs for Neglected Diseases initiative (DNDi) (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

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

Alternative name(s)

EC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Belgium

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

2006 results in http://www.ncbi.nlm.nih.gov/pubmed/17054744

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

20/10/2016: Plain English summary added.