Condition category
Infections and Infestations
Date applied
21/01/2008
Date assigned
23/01/2008
Last edited
17/07/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Paul Newton

ORCID ID

Contact details

Microbiology Laboratory
Mahosot Hospital
Vientiane
100
Laos
paul@tropmedres.ac

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

LMC-18

Study information

Scientific title

Thiamin treatment and Plasmodium falciparum malaria in Laos

Acronym

TIP

Study hypothesis

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

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

Study design

An exploratory, double-blind, parallel group, placebo-controlled trial, randomised (variable blocks), superiority trial

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, beriberi

Intervention

Treatment arm:
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.

Placebo arm:
Physically identical placebo containing no thiamin.

Intervention type

Drug

Phase

Not Applicable

Drug names

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

01/06/2008

Overall trial end date

01/12/2011

Reason abandoned

Eligibility

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

Participant type

Patient

Age group

Other

Gender

Both

Target number of participants

814

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

01/06/2008

Recruitment end date

01/12/2011

Locations

Countries of recruitment

Laos

Trial participating centre

Microbiology Laboratory
Vientiane
100
Laos

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Churchill Hospital
CCVTM
Headington
Oxford
OX3 7LJ
United Kingdom
research.services@admin.ox.ac.uk

Sponsor type

University/education

Website

http://www.jr2.ox.ac.uk/ndm/Tropical_Medicine

Funders

Funder type

Charity

Funder name

The Wellcome Trust (UK) (grant ref: 066828)

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

2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22681769
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25027701

Publication citations

  1. Results

    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.

  2. Results

    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.

Additional files

Editorial Notes