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 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
28/07/2004
Overall trial end date
01/10/2005
Reason abandoned (if study stopped)
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
Funders
Funder type
Charity
Funder name
Wellcome Trust
Alternative name(s)
Wellcome
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
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 http://www.ncbi.nlm.nih.gov/pubmed/17054744
Publication citations
-
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.