Plain English Summary
Background and study aims
This study aims to find out whether chloroquine reduces the number of dengue viruses in a patient with a dengue infection. Dengue fever is the most common mosquito-transmitted viral disease in humans. Severe forms of dengue infection can result in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Currently, no vaccine or treatment exists except for supportive care. Studies have shown that the dengue virus needs a certain level of acidity (or pH) in order to enter into human cells. Chloroquine is a drug known to affect other viruses that require a pH-dependent step to enter human cells. Therefore, this study will test whether chloroquine shows potential to be a treatment for dengue-infected patients by reducing the number of viruses that infect cells.
Who can participate?
Eligible patients have uncomplicated signs of dengue fever (fever, headache, aches, rash) after a standard clinical examination, with a history of symptoms less than 5 days. They must be over 14 years of age and weigh more than 45 kg, with no previous history of hypersensitivity to chloroquine, and cannot be pregnant or be receiving therapy for other disorders.
What does the study involve?
Prior to recruitment, all patients will have a standard clinical examination, a chest x-ray and a blood test to count the number of dengue viruses. The patients will then be randomly allocated to either group A or group B. Group A patients will receive chloroquine treatment and group B patients will receive a placebo (dummy) tablet. The study will then compare dengue outcomes in patients receiving placebo versus chloroquine by measuring fever clearance time and the time until tests show no presence of dengue virus. All adverse events will be fully recorded including duration, severity, outcome and relationship to study drug. Liver function tests will be repeated at discharge in all patients.
What are the possible benefits and risks of participating?
The Oxford University Clinical Research Unit will provide the drugs and support for the trial, and all patients will receive standard dengue clinical examination, diagnosis and treatment. Chloroquine side effects include nausea, vomiting, diarrhea, abdominal cramps and headache.
Where is the study run from?
The study is run by researchers at the Oxford University Clinical Research Unit (Viet Nam) and the Hospital for Tropical Diseases (Ho Chi Minh City, Viet Nam).
When is the study starting and how long is it expected to run for?
The study began in July 2006 and ended in March 2008.
Who is funding the study?
The Wellcome Trust (UK).
Who is the main contact?
The Clinical Trials Unit at the Oxford University Clinical Research Unit - Viet Nam
Tel: +84 (0)839 241 983
Trial website
Contact information
Type
Scientific
Primary contact
Dr Cameron Simmons
ORCID ID
Contact details
Oxford University Clinical Research Unit
Hospital for Tropical Diseases
Ho Chi Minh City
District 5
Viet Nam
+84 (0)8 9237954
csimmons@oucru.org
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
061330
Study information
Scientific title
A randomised, double-blind, placebo-controlled trial of chloroquine for treatment of dengue
Acronym
EF
Study hypothesis
The primary purpose of this protocol is to evaluate chloroquine as compared to placebo in the treatment of dengue with the hypothesis that chloroquine will decrease viral replication and therefore may confer a clinical advantage. This protocol will also attempt to define differences in clinical manifestations, the relationship between chloroquine concentrations and viral dynamics, and the pathogenesis of dengue, which may help to improve the treatment of this disease.
Ethics approval
1. Hospital for Tropical Diseases, 20/04/2006
2. Oxford Tropical Research Ethical Committee, 23/02/2006, ref: 005-06
Study design
Double-blind randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Dengue fever
Intervention
Patients will receive placebo (starch) or 600 mg chloroquine on day one and two, then 300 mg on day three. Delivery is by oral ingestion.
Intervention type
Drug
Phase
Not Applicable
Drug names
Chloroquine
Primary outcome measure
The primary objective is to compare the antiviral efficacy of chloroquine in the treatment of dengue infections as assessed by negative Reverse Transcriptase (RT)-Polymerase Chain Reaction (PCR) detection of viral Ribonucleic Acid (RNA) in plasma and clearance of NS-1 from blood.
Secondary outcome measures
No secondary outcome measures
Overall trial start date
01/07/2006
Overall trial end date
30/03/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Any adult patient (either sex) with dengue who gives consent. We plan to enrol all patients with suspected dengue presenting within three days of illness onset.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
220
Participant exclusion criteria
No consent
Recruitment start date
01/07/2006
Recruitment end date
31/01/2008
Locations
Countries of recruitment
Viet Nam
Trial participating centre
Oxford University Clinical Research Unit
Ho Chi Minh City
District 5
Viet Nam
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom
+44 (0)1865 270143
research.services@admin.ox.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Wellcome Trust
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
International organizations
Location
United Kingdom
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
2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20706626
Publication citations
-
Results
Tricou V, Minh NN, Van TP, Lee SJ, Farrar J, Wills B, Tran HT, Simmons CP, A randomized controlled trial of chloroquine for the treatment of dengue in Vietnamese adults., PLoS Negl Trop Dis, 2010, 4, 8, e785, doi: 10.1371/journal.pntd.0000785.