Dr Paul Newton
Thiamin treatment and Plasmodium falciparum malaria in Laos
The frequency of adverse events after antimalarial therapy will be significantly lower in those who receive thiamin supplementation in comparison to those who do not.
Ethics approval received from:
1. Oxford Tropical Research Ethics Committee (UK) on the 21st August 2007 (ref: OXTREC 026-07)
2. Lao PDR National Ethics Committee for Health Research (NECHR) on the 18th July 2007
An exploratory, double-blind, parallel group, placebo-controlled trial, randomised (variable blocks), superiority trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Oral thiamin (5 mg tablet) two tablets immediately after antimalarial drugs, followed by two tablets daily for 7 days followed by one tablet daily until day 42.
Physically identical placebo containing no thiamin.
Primary outcome measures
To determine whether the frequency of adverse events, after antimalarial therapy, are significantly lower in those who receive thiamin supplementation in comparison to those who do not.
For the primary endpoint the outcome measure will be assessed clinically before treatment and on each day until discharge and then on days 7, 14, 21, 28, 38 and 42 after start of treatment.
Secondary outcome measures
To determine the frequency of biochemical thiamin deficiency and whether this is related to the clinical severity of disease and the extent of resolution of deficiency between those who do and do not receive thiamin supplementation.
The secondary outcome measures will be assessed by red cell transketolase assays of washed red cell samples on day 0 and 42.
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Written fully informed consent given by patients and in the case of children, by parents or guardians
2. Males and females of any age
3. Microscopically confirmed Plasmodium falciparum infection with history of fever. Multiple Plasmodium species infections will be included.
4. Willingness and ability to comply with the study protocol for the duration of the 42 days follow up
5. Did not take a full course of any antimalarial drugs in previous three days
Target number of participants
Participant exclusion criteria
1. Known hypersensitivity to thiamin
2. Presence of intercurrent non-malarial illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study
3. Clinically apparent suspected thiamin deficiency (beriberi), which will be defined (World Health Organization [WHO] 1999) as:
3.1. Children less than 5 years: peripheral oedema or clinical evidence for pulmonary oedema, or cyanosis or classical hoarse cry
3.2. Adults and children greater than 5 years: peripheral oedema or clinical evidence for pulmonary oedema or lower limb paraesthesia or, before malarial illness, difficulty in rising from squatting position (it will be difficult to distinguish features of wet beriberi, such as peripheral and pulmonary oedema, from consequences of malaria, such as severe anaemia, acute respiratory distress syndrome [ARDS] and pneumonia. Clinicians will be cautious and classify the patient as having beriberi if there is doubt).
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
The Wellcome Trust (UK) (grant ref: 066828)
Funding Body Type
Funding Body Subtype
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
Mayxay M, Khanthavong M, Chanthongthip O, Imwong M, Pongvongsa T, Hongvanthong B, Phompida S, Vanisaveth V, White NJ, Newton PN, Efficacy of artemether-lumefantrine, the nationally-recommended artemisinin combination for the treatment of uncomplicated falciparum malaria, in southern Laos., Malar. J., 2012, 11, 184, doi: 10.1186/1475-2875-11-184.
Mayxay M, Khanthavong M, Cox L, Sichanthongthip O, Imwong M, Pongvongsa T, Hongvanthong B, Phompida S, Vanisaveth V, White NJ, Newton PN, Thiamin supplementation does not reduce the frequency of adverse events after anti-malarial therapy among patients with falciparum malaria in southern Laos., Malar. J., 2014, 13, 275, doi: 10.1186/1475-2875-13-275.