Investigating and Modelling the Natural History of Dengue in Hospitalised Patients to Improve Future Research (DENEM)

August 28, 2026 updated by: Liverpool School of Tropical Medicine

Dengue Evaluation of Multi-State Models (DENEM Study): A Prospective Observational Study of Patients Hospitalised With Dengue Vascular Leak in Nha Trang, Vietnam, to Develop Novel Statistical Methodology

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:

  1. How does dengue illness change over time, particularly the development and recovery of vascular leak (where blood vessels leak)?
  2. Can a new statistical approaches describe dengue illness accurately and be suitable for use in future clinical trials?
  3. Which blood biomarkers are associated with worsening or improving dengue illness, and what do they tell us about how severe dengue develops? Could these blood biomarkers act as reliable indicators of disease severity and recovery, making them useful outcome measures in future dengue treatment trials?
  4. How accurately do simplified diagnostic tests identify dengue compared with laboratory reference methods, and are they suitable for use in research and clinical settings in low- and middle-income countries?

Participants will be observed without any intervention throughout their hospitalisation. Participants will be be asked to provide informed consent for:

  • Recording of their routine clinical data
  • Regular blood tests
  • Regular ultrasound scans
  • A follow up appointment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
235

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Vietnam
      • Nha Trang, Vietnam
        • Nagasaki University Vietnam Research Station, Nha Trang
        • Contact:
        • Principal Investigator:
          • Lay Myint Yoshida, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Patients presenting to Khánh Hòa Hospital of Tropical Diseases, Nha Trang, Vietnam.

Description

Inclusion Criteria (hospitalised cohort):

  • Meet the 2009 WHO criteria for dengue with warning signs or severe dengue AND
  • Are being admitted as an inpatient AND
  • Have documented standard-of-care laboratory confirmation of dengue (defined as either positive by molecular assay (e.g. reverse transcription polymerase chain reaction) OR positive by antigen testing (non-structural protein-1) OR positive Immunoglobulin M (IgM) combined with clinical diagnosis of dengue by attending physician. AND
  • Were born in Vietnam (only for platelet phenomics substudy)

Inclusion Criteria (diagnostic control cohort):

  • Have a documented fever at assessment AND
  • Have a documented negative standard-of-care dengue test, with no clinical diagnosis of dengue AND
  • Were born in Vietnam (only for platelet phenomics substudy)

Inclusion Criteria (platelet control cohort):

  • Vietnamese-born adults ≥16 years of age with no history of febrile illness in the preceding 14 days.

Exclusion Criteria:

  • Receiving an experimental dengue treatment during their illness.
  • Inability to provide written, informed consent AND no legal guardian able to provide written, informed consent in the event of incapacity.
  • Clinician-determined unsuitability for recruitment.

Exclusion Criteria (platelet substudy only):

  • Any non-steroidal anti-inflammatory, antiplatelet or anticoagulant medication received in preceding 7 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Hospitalised Cohort
Patients hospitalised with dengue with warning signs or severe dengue
Diagnostic Control Cohort
Patients with non-dengue febrile illness
Platelet Control Cohort
Healthy Vietnamese volunteers

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Degree of vascular leak
Time Frame: From enrollment until day 10 of illness, or discharge
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.
From enrollment until day 10 of illness, or discharge

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Multi-state model evaluation - precision
Time Frame: Assessed at 3 days and 5 days post admission
Confidence in model parameters: 95% confidence interval width around 3- and 5-day probabilities of all state transition pairs (probability with 95% confidence interval)
Assessed at 3 days and 5 days post admission
Multi-state model evaluation: model fit
Time Frame: From enrollment until day 10 of illness or discharge
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)
From enrollment until day 10 of illness or discharge
Viral dynamics
Time Frame: From enrollment until day 10 of illness, or discharge
Dengue viral load by reverse-transcriptase polymerase chain reaction (copies per microlitre)
From enrollment until day 10 of illness, or discharge
Degree of thrombocytopenia
Time Frame: From enrollment until day 10 of illness or discharge
Presence and severirty of thrombocytopenia (none, moderate, severe) per Tomashek et al. 2018 consensus definitions - measured by platelet count (10^9/L)
From enrollment until day 10 of illness or discharge
Degree of bleeding
Time Frame: From enrollment until day 10 of illness or discharge
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.
From enrollment until day 10 of illness or discharge
Modified sequenetial organ failure score (mSOFA)
Time Frame: From enrollment until day 10 of illness or discharge
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)
From enrollment until day 10 of illness or discharge
Volume of Intravenous Fluid Received in 24 hours
Time Frame: From enrollment until day 10 of illness or discharge
Fluid type and volume (mL)
From enrollment until day 10 of illness or discharge
Dengue Clinical Severity
Time Frame: From enrollment until day 10 of illness or discharge
Dengue clinical severity classification per WHO 2009 criteria (dengue without warning signs, dengue with warning signs, severe dengue)
From enrollment until day 10 of illness or discharge
Concentration of a panel of plasma biomarkers of endothelial dysfunction, inflammation and platelet dysfunction.
Time Frame: From enrollment until day 10 of illness, or discharge
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
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.
Time Frame: From enrollment until day 10 of illness or discharge
Correlation of biomarker values with clinical and model outcomes
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.
Time Frame: At enrollment
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.
At enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Liverpool School of Tropical Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Nagasaki University
Pasteur Institute, Nha Trang

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 5, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 2, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0416

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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