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

Study Overview
=================
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.

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

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)


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SICU cohort<br>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)<br>* 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).<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Severe sepsis in patients with neurological haemorrhage