Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
CTU04DXAPR08
Study information
Scientific title
Acronym
Study hypothesis
We hypothesise that factors other than enhancing antibody level affect viral load and dengue severity. To identify such factors we will focus on patients with symptomatic primary dengue who by definition lack pre-existing dengue antibodies.
Ethics approval
1. The Oxford Tropical Medicine Research Ethics Committee (OXTREC) (UK) gave approval on the 25th June 2008 (ref: 26/08)
2. Pending as of 25/07/2008 from the NIITD Ethical Committee (Viet Nam)
Study design
Observational descriptive study
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Hospitals
Trial type
Screening
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Dengue fever
Intervention
Because dengue is seasonal, most of the dengue patients will be recruited over a period of some 6 months, from May to September. During this time, patients will be recruited and then followed up. If some patients have a persistent abnormality that may be dengue related, e.g. evidence of reduced cardiac function, they will be followed up until either their abnormality stabilises or for at least one year. Depending on recruitment, the study may be extended to cover a second dengue season.
Descriptive analyses of the endpoints will consist of proportions for categorical data and means (SD, 95% CIs) and/or median (inter-quartile and full ranges) for continuous data supplemented by graphical displays where relevant. Simple correlations (Pearson's correlation coefficient or Spearman's rho) will be made between continuous data, e.g. cytokine and complement concentrations. Comparative analyses will be between:
1. Patients who develop severe dengue (DHF/DSS) versus those who do not, and
2. Patients with 10 and 20 infections
For categorical data, the comparisons will be by chi squared. For continuous data, the student's 't' test for normally distributed data or Mann Whitney U tests for skewed data.
Other analyses:
1. Full blood count, differential white cell count
2. Clotting studies - prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and d-dimers. Antithromin III, protein C and S may be done later on stored plasma.
3. Sodium, potassium, urea, creatinine, glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), total creatine kinase (CK), creatine kinase myocardial bands (CKmb) fraction, cardiac troponins, total bilirubin, total protein, albumin
4. Quantitative protein electrophoresis
5. Urine analysis
6. Radiology
7. Electrocardiograms (ECGs)
8. Echocardiograms (ECHO)
9. Spirometry (for lung function)
10. Virology studies
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measure
1. Proportions of patients with 10 (Immunoglobulin M and Immunoglobulin G ratio [IgM:IgG] greater than or equal to 1.8:1) or 20 (IgM:IgG ratio less than 1.8:1) infections*
2. Proportions of patients who develop severe dengue (DHF/DSS)
* as noted in section 4.3 of the protocol; these definitions may change
As it is a descriptive study the data will be analysed once all data have been collected. There are no timepoints for interim analyses.
Secondary outcome measures
1. The ECG abnormalities of rate, rhythm and ECG intervals (PR, QRS, QT)
2. Cardiac function (echocardiogram) - ejection fraction (%), cardiac index (L/min/m^2) and rate corrected velocity of circumferential ventricular fibre shortening adjusted for left ventricular wall stress (kilodyne/cm^2)
3. Lung volumes: forced vital capacity (FVC) in litres, forced expiratory volume in one second (FEV1) in litres/s, and the FEV1/FVC ratio
4. The proportions of patients with pleural effusions and ascites
5. Dengue viral load at baseline and over time
6. NS1 concentration at baseline and over time
7. Cytokine, complement and anti-dengue neutralising antibody concentrations at baseline and over time
8. Fractional clearances of albumin and other plasma proteins
As it is a descriptive study the data will be analysed once all data have been collected. There are no timepoints for interim analyses.
Overall trial start date
01/08/2008
Overall trial end date
30/01/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. A patient of any age, including pregnant women, with suspected dengue infection using the World Health Organization (WHO) criteria below:
1.1. History of fever and two or more of the following:
1.1.1. Headache
1.1.2. Retro-orbital pain
1.1.3. Myalgia
1.1.4. Arthralgia
1.1.5. Rash
1.1.6. Haemorrhagic manifestation
1.1.7. Leukopaenia
2. Informed consent signed by the patient or parent/guardian
Participant type
Patient
Age group
Other
Gender
Both
Target number of participants
200
Participant exclusion criteria
Does not comply with the above inclusion criteria.
Recruitment start date
01/08/2008
Recruitment end date
30/01/2009
Locations
Countries of recruitment
Viet Nam
Trial participating centre
Oxford University Clinical Research Unit
Hanoi
-
Viet Nam
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
Clinical Trials and Research Governance
Manor House
John Radcliffe Hospital
Headington
Oxford
OX3 9DZ
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
The Wellcome Trust (UK) (grant ref: 077078)
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
Basic results (scientific)
Publication list