ISRCTN - ISRCTN38002730: A research study of the role of chloroquine in treating patients with dengue

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

http://www.ox.ac.uk

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

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data