An observational study in Dengue, sponsored by Liverpool School of Tropical Medicine. Not yet recruiting at 1 site in Vietnam. Open to participants aged 16 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-02.
Sponsored by Liverpool School of Tropical Medicine · Observational
The goal of this observational study is to investigate the natural history of dengue in hospitalised patients in Vietnam, to better understand the disease process, and utilise the data to improve future clinical trials. The main questions it aims to answer are:
In participants hospitalised with dengue in Vietnam:
Participants will be observed without any intervention throughout their hospitalisation. Participants will be be asked to provide informed consent for:
Dengue is a life-threatening infection caused by a virus, spread between humans by the bite of mosquitoes. It is present throughout the tropics, including in Vietnam, where cases have dramatically increased in recent years. Dengue causes severe illness predominantly through vascular leak, where patients' blood vessels break down, becoming leaky, leading to fluid from the vessels moving into tissues and organs such as the lungs.
However, it is still not fully understand how the virus causes vascular leak, or in which patients it is most likely to occur in. There are no licensed treatments for vascular leak. This is because the mechanism of vascular leak is incompletely understood, making therapeutic targeting difficult. Additionally, when drugs are trialled, many trials have been poorly designed and not included enough patients.
To answer our research questions, the investigators will recruit 142 patients admitted to hospital with dengue in Nha Trang, Vietnam who have dengue vascular leak. If they are happy to enter the study, data will be recorded that is already being collected as part of their hospital admission; this will include clinical data (such as blood pressure, pulse and treatments given) and the results of their blood tests. Investigators will also run tests beyond what they would normally have in hospital; this will include the results of regular ultrasound scans and biomarker blood tests (small molecules that can be detected in their blood in response to stress and vascular leak). Most patients have blood tests daily in hospital, and clinicians will aim to take the extra tubes of blood required at the same time, to minimise the number of extra procedures requested from participants.
Investigators will put this data it into a statistical model of dengue vascular leak they have been developing, called a multi-state model. These models have previously been used in other areas of medicine, but this would be their first application in dengue and infectious diseases research. Multi-state models aim to track how patients move through different stages of illness over time. Models such as this make better use of all the information collected during a patient's illness. Rather than only looking at a single outcome, such as whether a patient had recovered by a certain day, or how long recovery took, they track how patients move through different stages of dengue over time and how long they spend in each stage. This may give a more complete picture of how treatments affect the course of illness. If successful, it could improve how future dengue clinical trials are designed, helping researchers detect whether new treatments work more quickly and with fewer volunteers.
Investigators will also use data and samples collected from this study to explore why vascular leak occurs and evaluate new ways of diagnosing dengue, particularly in low-resource settings. To achieve this, investigators will need to compare patients who have dengue to people who have not got dengue, looking for differences. As such 93 people who do not have dengue (called "control" participants) will be recruited. Some will have a fever from another cause, and others will be healthy volunteers. Comparing these control populations with patients who have dengue helps us understand which findings are specific to dengue and how accurate new dengue tests are. People in these groups will only have a single small blood sample taken and will not receive any treatment or need follow-up visits.
Overall, this study aims to support the development of better treatments and more efficient clinical trials for dengue.
Patients presenting to Khánh Hòa Hospital of Tropical Diseases, Nha Trang, Vietnam.
Inclusion Criteria (hospitalised cohort):
Inclusion Criteria (diagnostic control cohort):
Inclusion Criteria (platelet control cohort):
Exclusion Criteria:
Exclusion Criteria (platelet substudy only):
Patients hospitalised with dengue with warning signs or severe dengue
Patients with non-dengue febrile illness
Healthy Vietnamese volunteers
Degree of vascular leak
Presence and severity of vascular leak (none, moderate, severe) per Tomashek et al. 2018 consensus definitions - composite of change of haematocrit from baseline, presence of ascites/pleural effusion by point of care ultrasound and presence of respiratory/cardiovascular compromise.
Time frame: From enrollment until day 10 of illness, or discharge
Multi-state model evaluation - precision
Confidence in model parameters: 95% confidence interval width around 3- and 5-day probabilities of all state transition pairs (probability with 95% confidence interval)
Time frame: Assessed at 3 days and 5 days post admission
Multi-state model evaluation: model fit
Goodness of fit of model compared to observed data, as assessed by Akaike information criteria (AIC) values, Bayesian information criteria (BIC) values and Likelihood-ratio test (p-value)
Time frame: From enrollment until day 10 of illness or discharge
Viral dynamics
Dengue viral load by reverse-transcriptase polymerase chain reaction (copies per microlitre)
Time frame: From enrollment until day 10 of illness, or discharge
Degree of thrombocytopenia
Presence and severirty of thrombocytopenia (none, moderate, severe) per Tomashek et al. 2018 consensus definitions - measured by platelet count (10\^9/L)
Time frame: From enrollment until day 10 of illness or discharge
Degree of bleeding
Presence and severirty of bleeding (none, moderate, severe) per Tomashek et al. 2018 consensus definitions - composite score measured by presence/absence of clinical bleeding, requirement for local intervention, cardiovascular compromise, requirement for blood transfusion.
Time frame: From enrollment until day 10 of illness or discharge
Modified sequenetial organ failure score (mSOFA)
mSOFA score composite score (0-24) with 6 systems assessed, each component contributing 0-4 points to the overal score. Systems assessed: respiratory system (peripheral saturations of oxygen/fraction inspired oxygen, mmHg), Coagulation (platelet count / microlitre), Liver function (Bilirubin, mg/dl), Cardiovascular system (mean arterial pressure / pulse pressure, mmHg), Central nervous system (glasgow coma score), renal function (creatinin, mg/dL or urine output, mL/day)
Time frame: From enrollment until day 10 of illness or discharge
Volume of Intravenous Fluid Received in 24 hours
Fluid type and volume (mL)
Time frame: From enrollment until day 10 of illness or discharge
Dengue Clinical Severity
Dengue clinical severity classification per WHO 2009 criteria (dengue without warning signs, dengue with warning signs, severe dengue)
Time frame: From enrollment until day 10 of illness or discharge
Concentration of a panel of plasma biomarkers of endothelial dysfunction, inflammation and platelet dysfunction.
Longitudinal measurement of biomarkers such as Syndecan-1, Angiopoietin 1/2, VCAM-1, CRP, Ferritin, platelet function assay, platelet-leucocyte aggregate assay, platelet receptor panel
Time frame: From enrollment until day 10 of illness, or discharge
Performance of plasma biomarkers of dengue vascular leak as robust secondary endpoints in future dengue interventional trials.
Correlation of biomarker values with clinical and model outcomes
Time frame: From enrollment until day 10 of illness or discharge
Performance of dengue diagnostic platforms, for use in participant screening in low- and middle-income countries.
Diagnostic accuracy of novel LAMP assay compared to reference standard and RDT: sensitivity, specificity and predictive values of diagnostic platforms against RT-PCR as reference and RDTs as standard of care.
Time frame: At enrollment
Plan to share: Yes — Anonymised study results will be made publicly available through scientific publications and, where appropriate, data repositories. Requests from bona fide researchers for access to de-identified participant-level data will be considered on a case-by-case basis, subject to applicable ethical approvals, participant consent, and local and institutional policies.
Supporting information: Study protocol, Analytic code
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Liverpool School of Tropical Medicine