Prospective Study for the Evaluation of Dengue Prognostic Biomarkers in Singapore

NCT04048837 | Completed DMC

• 1 other identifier: PrognosDen
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 3

Brief Summary

World Health Organisation (WHO) has identified Dengue as the fastest spreading mosquito-borne disease in the world. This study follows on from the National Medical Research Council STOP Dengue Translational and Clinical Research flagship grant. Differential serum concentrations of alpha2-macroglobulin (A2M), chymase (CMA1) and vascular endothelial growth factor A (VEGFA) were discovered to accurately identify dengue patients who will develop severe disease from those who will not, prior to the development of severe complications. By identifying patients at risk of developing severe disease in advance, these patients can be monitored more closely to provide more timely fluid interventions, and hopefully further reduce fatality rate. At the same time, more patients who are not at risk can be managed as outpatients to further minimize unnecessary hospitalization costs and wastage of healthcare resources. After discovery of the Dengue prognostic biomarkers, a multivariate logistic regression predictive model was built from a small retrospective derivative cohort (50 subjects), followed by validation using a small prospective validation cohort (50 subjects). The model had a receiver operating characteristic (ROC) curve AUC (area under the curve) of 0.944, and a sensitivity and specificity of 90% and 91% during validation, respectively. The premise of this study is to validate our observations in a larger prospective cohort (200 subjects). At the same time, we would like to better understand the characteristics of the Dengue prognostic biomarkers, especially whether there are situations in which the biomarkers cannot predict Dengue Haemorrhagic Fever (DHF)/ Dengue Shock Syndrome (DSS) and/or Severe Dengue (SD) and how the biomarkers can further improve the cost-effectiveness of the clinical management of Dengue patients.

Conditions

Dengue Hemorrhagic Fever; Dengue Shock Syndrome; Severe Dengue

Keywords

Dengue

Outcome Measures

Primary Outcomes (1)

• Concentration of serum A2M, CMA1 and VEGFA will be use to predict whether a dengue patient will develop severe disease as defined by WHO 1997 and WHO 2009 classifications.

  Blood will be drawn for measurements of serum concentrations of biomarkers via quantitative enzyme-linked immunosorbent assays (ELISA).

  7 days

Secondary Outcomes (4)

• Number of participants develop Dengue Haemorrhagic fever (DHF) within study periods

  7 days

• Number of participants develop Dengue Shock Syndrome (DSS) within study periods

  7 days

• Number of participants develop Severe Dengue within study periods

  7 days

• Cost of dengue treatments for adoption of such a dengue prognostic technology in hospital

  7 days

Eligibility Criteria

• Age: 21 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from patients presenting themselves to the emergency departments, outpatient clinic or inpatient wards of the participating sites, and who are diagnosed by laboratory tests to be infected with Dengue. Delegated research staff will screen laboratory-confirmed dengue patients with inclusion/exclusion criteria. Each participant will be given an information sheet and informed consent will obtained from him/her before any study procedures.

You may qualify if:

• Confirmed Dengue i.e. laboratory confirmation of acute Dengue for this current disease episode by either (i) Positive polymerase chain reaction (PCR) for viral ribonucleic acid (RNA), or (ii) Positive NS1 antigen test with a compatible clinical syndrome
• At least 21 years of age based on his/her birthday, and
• Willing and able to give informed consent.

You may not qualify if:

• Already classified as having Dengue Haemorrhagic Fever or Dengue Shock Syndrome (WHO 1997 classification) or severe Dengue (WHO 2009 classification) when they first present themselves to the hospital.
• Assessed by Investigators to be unlikely to comply with trial procedures.
• Have known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the past 6 months or long term corticosteroid therapy.
• Have received blood or blood-derived products in the past three months that might interfere with the assessment of the biomarker responses.
• Have participated in another clinical trial investigating a vaccine or drug in the four weeks preceding the study.
• Have received any vaccine in the four weeks preceding the study.
• Are deprived of freedom by an administrative or court order or in an emergency setting or hospitalized without his/her consent.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Tan Tock Seng Hospital: collaborator
• Ng Teng Fong General Hospital: collaborator

Study Sites (3)

Tan Tock Seng Hospital

Singapore, 308433, Singapore

Location

Ng Teng Fong General Hospital

Singapore, 609606, Singapore

Location

National University Hospital

Singapore, Singapore

Location

Related Publications (5)

• Lee LK, Earnest A, Carrasco LR, Thein TL, Gan VC, Lee VJ, Lye DC, Leo YS. Safety and cost savings of reducing adult dengue hospitalization in a tertiary care hospital in Singapore. Trans R Soc Trop Med Hyg. 2013 Jan;107(1):37-42. doi: 10.1093/trstmh/trs009.

  PMID: 23296696 BACKGROUND

• Ingram PR, Mahadevan M, Fisher DA. Dengue management: practical and safe hospital-based outpatient care. Trans R Soc Trop Med Hyg. 2009 Feb;103(2):203-5. doi: 10.1016/j.trstmh.2008.07.007. Epub 2008 Aug 29.

  PMID: 18760815 BACKGROUND

• Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GR, Simmons CP, Scott TW, Farrar JJ, Hay SI. The global distribution and burden of dengue. Nature. 2013 Apr 25;496(7446):504-7. doi: 10.1038/nature12060. Epub 2013 Apr 7.

  PMID: 23563266 BACKGROUND

• Brady OJ, Gething PW, Bhatt S, Messina JP, Brownstein JS, Hoen AG, Moyes CL, Farlow AW, Scott TW, Hay SI. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis. 2012;6(8):e1760. doi: 10.1371/journal.pntd.0001760. Epub 2012 Aug 7.

  PMID: 22880140 BACKGROUND

• Chawla S, Sahoo SS, Singh I, Verma M, Gupta V, Kumari S. Dengue vaccine: come let's fight the menace. Hum Vaccin Immunother. 2015;11(2):474-6. doi: 10.4161/21645515.2014.981077.

  PMID: 25695523 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma and serum sample will be stored if patient agreeable to keep for future research.

MeSH Terms

Conditions

Severe Dengue; Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Officials

• Sophia Archuleta

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2018
• First Posted: August 7, 2019
• Study Start: July 30, 2018
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: September 13, 2019

Record last verified: 2019-09

Locations

SG (3)