Clinical trial NCT04624945: DetectIon of Severe Sepsis In PATients With Neurological haemorrhagE (The DISSIPATE Study)
Official title: DetectIon of Severe Sepsis In PATients With Neurological haemorrhagE (The DISSIPATE Study)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sepsis
Hemorrhage Brain
Keywords: Severe sepsis in patients with neurological haemorrhage
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
Collaborators: name: Sysmex Asia Pacific
First posted: 2020-11-12
Enrollment: 150
Sex: ALL
Minimum age (years): 21
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: SICU stay from day 1 to day 5 through to 2 years of blood test completion
Secondary outcomes:
measure: 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.
timeFrame: SICU stay from day 1 to day 5 through to 2 years of blood test completion
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital, Singapore
Study officials:
affiliation: National University Hospital, Singapore
name: Will NH Loh, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Crit Care. 2010;14(1):R15. doi: 10.1186/cc8872. Epub 2010 Feb 9.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.