DetectIon of Severe Sepsis In PATients With Neurological haemorrhagE (The DISSIPATE Study) (DISSIPATE)

The research study is to explore novel early predictors and validation of laboratory parameters in the management of sepsis in critically ill patients especially with brain injuries and systemic inflammatory response syndrome (SIRS).

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Hemorrhage Brain
• Intervention / Treatment: Diagnostic test: APTT CWA (Activated partial thromboplastin time clot waveform analysis), Procalcitonin and Serological/Inflammatory markers (KL-6, SPA, MIG, Presepsin)

Detailed Description

This is a prospective observational study. 150 subjects with the admission diagnosis of neurological haemorrhage (e.g. subarachnoid haemorrhage, intracerebral haemorrhage etc), admitted to SICU of National University Hospital, Singapore, who are expected to stay for more than 48 hours, will be recruited and enrolled. No adverse events are expected as a result of this study as patients do not deviate from the current standard of care. Frequency of blood sampling will be stipulated at day 1/2/3/4/5 to draw clinical relevance. An additional 0.5 tablespoonful (7.7ml) of blood will be taken daily from each subject as well as residual blood from routine laboratory test blood samples. In total, an additional volume of 2.5 tablespoonful (38.5ml) of blood will be collected from each subject over a period of 5 days. Residual blood refers to any leftover blood samples collected for routine laboratory tests which will be shared and used to carry out additional blood tests. All ICU patients will have arterial lines inserted as part of routine care, so there will not be pain from the blood sampling. In the current study, measurements will be made on the routine laboratory haematology, coagulation and immunoassay analyzers. Research blood parameters that are not usually reported as indicated in the background section will be used for the correlation and association analysis to sepsis. In addition, the study team will also be collecting clinical and demographic data of recruited subjects from medical records for purposes of this study.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Will NH Loh, MBBS; Phone Number: 6772 4208; Email: Will.Loh@nus.edu.sg
• Study Contact Backup: Name: Christina YC Yip, PhD; Phone Number: 67724109; Email: christina_yip@nuhs.edu.sg

Study Locations

• Singapore
  • Singapore, Singapore, 119074
    • Recruiting
    • National University Hospital, Singapore
    • Contact: Will NH Loh, MBBS; Phone Number: 6772 4208; Email: Will.Loh@nus.edu.sg
    • Contact: Christina YC Yip, PhD; Phone Number: 67724109; Email: christina_yip@nuhs.edu.sg
    • Principal Investigator: Will NH Loh, MBBS
    • Sub-Investigator: Christina YC Yip, PhD
    • Sub-Investigator: Eng Soon Yap, MBBS
    • Sub-Investigator: Shir Ying Lee, MBBS
    • Sub-Investigator: Jiayi Shen, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is a prospective observational study. 150 subjects with the admission diagnosis of neurological haemorrhage (e.g. subarachnoid haemorrhage, intracerebral haemorrhage etc), admitted to SICU of National University Hospital, Singapore, who are expected to stay for more than 48 hours, will be recruited and enrolled.

Description

Inclusion Criteria:

• Adults 21 years and above
• Clinical/radiological suspicion or confirmation of neurological haemorrhage

Exclusion Criteria:

• Age below 21 years
• Prisoners
• Known pregnancy
• Do-not-attempt resuscitation status
• Requirement for immediate surgery
• Active chemotherapy/neutropenia (Neutrophil count <1.0 x 109/L)
• Immuno-compromised
• Haematological malignancy
• Treating physician deems aggressive care unsuitable
• Unable to provide informed consent or comply with study requirements

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

SICU cohort; 150 subjects with the admission diagnosis of neurological haemorrhage (e.g. subarachnoid haemorrhage, intracerebral haemorrhage etc), admitted to SICU of National University Hospital, Singapore, who are expected to stay for more than 48 hours, will be recruited and enrolled. Frequency of blood sampling will be stipulated atday 1/2/3/4/5 to draw clinical relevance. An additional 0.5 tablespoonful (7.7ml) of blood will be taken daily from each subject as well as residual blood from routine laboratory test blood samples.

Diagnostic test: APTT CWA (Activated partial thromboplastin time clot waveform analysis), Procalcitonin and Serological/Inflammatory markers (KL-6, SPA, MIG, Presepsin); Primary Aim: To validate the use of APTT CWA (Activated partial thromboplastin time clot waveform analysis) and ICIS (Intensive Care Infection Score), as early sepsis markers for neurosurgical ICU patients suffering subarachnoid haemorrhage, traumatic brain injury and other intracranial haemorrhages. Secondary Aim: To examine the evolution of CWA, immuno-parameters (KL-6, SP-A, MIG, presepsin) and various WBC (white blood cell count) activation markers over the time in relation to diagnosis of sepsis, development of positive blood cultures and mortality or recovery. Blood parameter measurements using a 3-part and 5-part differential analyser will be performed. KL-6, SP-A, MIG, presepsin are serum biomarkers - MIG (Monokine induced by gamma interferon), SP-A (Surfactant protein A), KL-6 (Krebs von den Lungen 6).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To validate the use of APTT CWA and ICIS, as early sepsis markers for neurosurgical ICU patients suffering subarachnoid haemorrhage, traumatic brain injury and other intracranial haemorrhages.	Activated Partial Thromboplastin Time (APTT) clot waveform analysis (CWA) by flow cytometry-based method	SICU stay from day 1 to day 5 through to 2 years of blood test completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To examine the evolution of CWA, immuno-parameters (KL-6, SP-A, MIG, presepsin) and various WBC activation markers over the time in relation to diagnosis of sepsis, development of positive blood cultures and mortality or recovery.	Blood parameter measurements using a 3-part and 5-part differential analyser will be performed.	SICU stay from day 1 to day 5 through to 2 years of blood test completion

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Collaborators: Sysmex Asia Pacific Pte Ltd
• Investigators: Principal Investigator: Will NH Loh, MBBS, National University Hospital, Singapore

Publications and helpful links

General Publications

• Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):762-74. doi: 10.1001/jama.2016.0288. Erratum In: JAMA. 2016 May 24-31;315(20):2237.
• Scaravilli V, Tinchero G, Citerio G; Participants in the International Multi-Disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage. Fever management in SAH. Neurocrit Care. 2011 Sep;15(2):287-94. doi: 10.1007/s12028-011-9588-6.
• Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Crit Care. 2010;14(1):R15. doi: 10.1186/cc8872. Epub 2010 Feb 9.
• Jang JH, Park WB, Lim YS, Choi JY, Cho JS, Woo JH, Choi WS, Yang HJ, Hyun SY. Combination of S100B and procalcitonin improves prognostic performance compared to either alone in patients with cardiac arrest: A prospective observational study. Medicine (Baltimore). 2019 Feb;98(6):e14496. doi: 10.1097/MD.0000000000014496.
• Pelinka LE, Petto H, Kroepfl A, Schmidhammer R, Redl HJEJoT. Serum Procalcitonin and S100B Are Associated with Mortality after Traumatic Brain Injury. European Journal of Trauma 2003; 29(5): 316-323.
• Chopin N, Floccard B, Sobas F, Illinger J, Boselli E, Benatir F, Levrat A, Guillaume C, Crozon J, Negrier C, Allaouchiche B. Activated partial thromboplastin time waveform analysis: a new tool to detect infection? Crit Care Med. 2006 Jun;34(6):1654-60. doi: 10.1097/01.CCM.0000217471.12799.1C.
• Sevenet PO, Depasse F. Clot waveform analysis: Where do we stand in 2017? Int J Lab Hematol. 2017 Dec;39(6):561-568. doi: 10.1111/ijlh.12724. Epub 2017 Sep 6.
• Zakariah AN, Cozzi SM, Van Nuffelen M, Clausi CM, Pradier O, Vincent JL. Combination of biphasic transmittance waveform with blood procalcitonin levels for diagnosis of sepsis in acutely ill patients. Crit Care Med. 2008 May;36(5):1507-12. doi: 10.1097/CCM.0b013e3181709f19.
• Toh CH, Ticknor LO, Downey C, Giles AR, Paton RC, Wenstone R. Early identification of sepsis and mortality risks through simple, rapid clot-waveform analysis. Implications of lipoprotein-complexed C reactive protein formation. Intensive Care Med. 2003 Jan;29(1):55-61. doi: 10.1007/s00134-002-1557-2. Epub 2002 Nov 22.
• Linssen J, Aderhold S, Nierhaus A, Frings D, Kaltschmidt C, Zanker K. Automation and validation of a rapid method to assess neutrophil and monocyte activation by routine fluorescence flow cytometry in vitro. Cytometry B Clin Cytom. 2008 Sep;74(5):295-309. doi: 10.1002/cyto.b.20422.
• Weimann K, Zimmermann M, Spies CD, Wernecke KD, Vicherek O, Nachtigall I, Tafelski S, Weimann A. Intensive Care Infection Score--A new approach to distinguish between infectious and noninfectious processes in intensive care and medicosurgical patients. J Int Med Res. 2015 Jun;43(3):435-51. doi: 10.1177/0300060514557711. Epub 2015 Apr 7.

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2020
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: November 5, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Severe sepsis in patients with neurological haemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Hemorrhage; Hemostatics; Coagulants; Thromboplastin
• Other Study ID Numbers: 2020/00020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No