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Trial registered on ANZCTR


Registration number
ACTRN12610000465055
Ethics application status
Approved
Date submitted
1/06/2010
Date registered
8/06/2010
Date last updated
12/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Continuous Monitoring of Patients with Severe Sepsis or Septic Shock using SeptiCyte (registered trademark) Lab and Procalcitonin Comparator to Determine the Relationship Between Inflammatory Index and Clinical Progression and Outcome Measures
Scientific title
Continuous Monitoring of Patients with Severe Sepsis or Septic Shock using SeptiCyte (registered trademark) Lab and Procalcitonin Comparator to Determine the Relationship Between Inflammatory Index and Clinical Progression and Outcome Measures
Secondary ID [1] 251946 0
Nil
Universal Trial Number (UTN)
U1111-1115-4269
Trial acronym
NA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe sepsis and septic shock 257498 0
Condition category
Condition code
Inflammatory and Immune System 257653 257653 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
SeptiCyte Lab is a diagnostic that uses a panel of 42 molecular (gene expression) biomarkers to distinguish sepsis from other non-infectious inflammatory conditions. For the purposes of this trial it will be used to monitor patients with severe sepsis or septic shock, over a 10-day period and while in the intensive care unit, to establish immune status. This test will be conducted using ribonucleic acid (RNA) isolated from 5ml of arterial or venous blood. Blood draws will be taken on Days 1, 2, 3, 5, 7 and 10 during this clinical trial.
Intervention code [1] 256592 0
Diagnosis / Prognosis
Comparator / control treatment
Procalcitonin (PCT) will be used a comparator monitoring device/biomarker. The PCT test is based on assessment of a single analyte/biomarker that is known to increase during systemic infection. PCT tests will be conducted at the same time as the SeptiCyte Lab test and will involve 1ml blood draws on Days 1, 2, 3, 5, 7 and 10 during this clinical trial.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 258559 0
To determine the relationship between the SeptiCyte Lab inflammatory index and change in clinical progression and outcome measures (Acute Physiology and Chronic Health Evaluation [APACHE II] and Sequential Organ Failure Assessment [SOFA] scores) between Days 1 to 10
Timepoint [1] 258559 0
Experimental testing will be conducted once only on Days 1, 2, 3, 5, 7 and 10. This will require a 6ml arterial or venous blood draw on each study day.
Secondary outcome [1] 264418 0
To determine the relationship between procalcitonin (PCT) and change in clinical progression and outcome measures (Acute Physiology and Chronic Health Evaluation [APACHE II] and Sequential Organ Failure Assessment [SOFA] scores) between Days 1 to 10.
Timepoint [1] 264418 0
Experimental testing will be conducted once only on Days 1, 2, 3, 5, 7 and 10. This will require a 6ml arterial or venous blood draw on each study day.
Secondary outcome [2] 264419 0
Development of a machine learning algorithm to predict sepsis status using sepsis gene expression biomarker signatures, clinical progression measures and survival outcomes.
Timepoint [2] 264419 0
Experimental testing will be conducted once only on Days 1, 2, 3, 5, 7 and 10. This will require a 6ml arterial or venous blood draw on each study day.
Secondary outcome [3] 264420 0
Expansion of the sepsis algorithm to incorporate therapeutic regimens.
Timepoint [3] 264420 0
Experimental testing will be conducted once only on Days 1, 2, 3, 5, 7 and 10. This will require a 6ml arterial or venous blood draw on each study day.

Eligibility
Key inclusion criteria
1. Aged over 18 years
2. Body Mass Index < 40
3. Clinical signs and symptoms of severe sepsis or septic shock. In brief, patients must be admitted to the intensive care unit with two or more signs of systemic inflammation within the last 24 hours, with a proven or suspected source of infection and the sepsis-induced dysfunction of at least one organ or system. The absence of positive culture results will not affect clinical diagnosis of sepsis.
Systemic Inflammatory Response (SIRS) Criteria: temperature >38°C or <36°C; heart rate >90 beats/min; respiratory rate >20 breathes/min or a partial pressure of carbon dioxide (PaCO2) of <4.3 kPa (<32 mm Hg) or mechanical ventilation; and a white blood cell count <4,000 cells/mm3 (<4 x 109 cells/L) or >12,000 cells/mm3 (>12 x 109 cells/L) or >10% immature neutrophils (band forms). (Consensus from the American College of Chest Physicians/ Society of Critical Care Medicine)
Infection Criteria: evidence of proven or suspected infection as demonstrated by one or more of the following: white cells in a normally sterile body fluid; perforated viscus; radiographic evidence of pneumonia in association with the production of purulent sputum; a syndrome related to a high risk of infection

Organ/System Dysfunction Criteria:

Cardiovascular – systolic arterial blood pressure of less than or equal to 90 mmHg or mean arterial pressure of less than or equal to 70 mmHg for >1 hr, despite adequate fluid resuscitation, adequate intravascular volume status or the use of vasopressors in an attempt to maintain a systolic pressure of greater than or equal to 90 mmHg or a mean arterial pressure of greater than or equal to 70 mmHg;
Pulmonary – partial pressure of arterial oxygen/inspired oxygen (PaO2/FiO2 ratio) less than or equal to 250 in the presence of other dysfunctional organs or systems or less than or equal to 200 if the lung is the only dysfunctional organ;
Renal – urine output of <0.5 ml/kg of body weight/ hr for 1 hour, despite adequate fluid resuscitation;
Unexplained Metabolic Acidosis – pH less than or equal to 7.30 or a base deficit of greater than or equal to 5.0 mmol/L in association with a plasma lactate level that is >1.5 times the upper limit of the local laboratory reference range
Haematologic – platelet count <80,000/mm3 (<80,000 microlitres), or platelet count has decreased by 50% in the 3 days preceding enrolment.
4. The patient and substitute health authority are fluent in English (both written and spoken) and the patient or substitute health authority are capable of providing informed consent to participate in the study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who have an autoimmune disease or other documented chronic immunological disorder e.g. systemic lupus erythmatosus (SLE), Crohn’s disease, rheumatoid arthritis, multiple sclerosis (MS), Type 1 Diabetes Mellitus
2. Oncology patients receiving chemotherapy within the last 3 months
3. Solid-organ transplant recipients

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be screened at the time of admission to the intensive care unit to assess whether they meet the criteria for severe sepsis or septic shock and none of the exclusion criteria. This is an observational monitoring trial and no experimental treatment is to be administered.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
29/05/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
70
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 257087 0
Government body
Name [1] 257087 0
AusIndustry
Country [1] 257087 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
ImmuneXpress Pty Ltd
Address
PO Box 1448
Toowong Qld 4066
Country
Australia
Secondary sponsor category [1] 256344 0
None
Name [1] 256344 0
Address [1] 256344 0
Country [1] 256344 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259112 0
Mater Health Services Human Research Ethics Committee
Ethics committee address [1] 259112 0
Room 235 Aubigny Place
Mater Misericordiae Health Services
Raymond Tce
South Brisbane Queensland 4101
Ethics committee country [1] 259112 0
Australia
Date submitted for ethics approval [1] 259112 0
16/06/2009
Approval date [1] 259112 0
21/10/2009
Ethics approval number [1] 259112 0
1400A
Ethics committee name [2] 259113 0
Royal Brisbane & Women's Hospital Human Research Ethics Committee
Ethics committee address [2] 259113 0
Herston Road
Herston Queensland 4029
Ethics committee country [2] 259113 0
Australia
Date submitted for ethics approval [2] 259113 0
23/09/2009
Approval date [2] 259113 0
21/11/2009
Ethics approval number [2] 259113 0
HREC/09/QRBW/295
Ethics committee name [3] 266623 0
Metro South Human Research Ethics Committee
Ethics committee address [3] 266623 0
Princess Alexandra Hospital, Ipswich Road Woollongabba Q 4102
Ethics committee country [3] 266623 0
Australia
Date submitted for ethics approval [3] 266623 0
01/11/2010
Approval date [3] 266623 0
04/02/2011
Ethics approval number [3] 266623 0
HREC/10/QPAH/246

Summary
Brief summary
Sepsis is a specific systemic inflammatory response to either a gram positive or gram negative bacterial or fungal infection. The cornerstone of sepsis diagnosis and prognosis for many decades has been identifying the causative circulating pathogen and quantitating single blood analytes to assess the patient’s physiological response to the pathogen. However, it is an individual’s immune system, which determines clinical escalation to septic shock and not the causative pathogen. Given that the immune response is complex and multifactorial there is a necessity for an assay that can expedite the early diagnosis of sepsis, as well as evaluate the individual’s response to therapy/management. Recent developments in biomolecular technologies using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) enable gene expression patterns to be translated into diagnostic pathology profiles and have the capacity to improve acute clinical management.
“Athlomics” development has characterised a panel of 42 inflammatory gene expression biomarkers that significantly correlate with incidence of sepsis using both equine and human models. Athlomics preliminary outcomes, using data sets from local clinical trials, suggest that this investigational diagnostic has a better than 95% accuracy of detecting sepsis in patients admitted to a tertiary clinical setting with an acute non-specific immunoinflammatory response, based on area under the curve calculations using receiver operator characteristics (ROC) analyses. This is an important finding, and indicates that the specificity of the Athlomics sepsis signature is well within the performance band required for clinical use. To improve the strength of this signal Gene Expression Omnibus (GEO) samples were compared with gene expression profiles from the sepsis cohort, demonstrating a specificity of greater than 99% based on ROC curves. The Athlomics sepsis signature was applied to all currently available GEO Genechip data for human whole blood studies and a subset of 168 control samples, including both healthy controls and controls with known conditions not expected to produce inflammatory signals. These outcomes, suggest that this assay is robust and has the capacity to be used in future clinical practice for the definitive diagnosis of sepsis. Moreover, it has the potential to be used in the practice of ‘personalised’ medicine, where an individual’s gene expression signature can be used to structure a specific clinical management plan, determine response to therapy and provide prognostic updates
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31245 0
Address 31245 0
Country 31245 0
Phone 31245 0
Fax 31245 0
Email 31245 0
Contact person for public queries
Name 14492 0
Dr Roslyn Brandon
Address 14492 0
1100 Dexter Avenue North, Suite 100
Seattle WA, 98109
Country 14492 0
United States of America
Phone 14492 0
+1 206 351 2662
Fax 14492 0
+1 206 273 7401
Email 14492 0
[email protected]
Contact person for scientific queries
Name 5420 0
Dr Allison Sutherland
Address 5420 0
PO Box 1448, Toowong Q 4066
Country 5420 0
Australia
Phone 5420 0
+61 423 684 659
Fax 5420 0
+617 3870 9101
Email 5420 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIA standardized protocol for the multiplex PCR technique Septifast® Roche for neonatal samples with suspected sepsis2012https://doi.org/10.1186/cc11766
Dimensions AIAdvance directives and end-of-life decision-making in the ICU: results from an observational study2012https://doi.org/10.1186/cc11695
Dimensions AIAMP-activated protein kinase preserves endothelial tight junctions in the coronary microcirculation during sepsis2012https://doi.org/10.1186/cc11717
Dimensions AIAssessment of clinical deterioration and progressive organ failure in moderate-severity emergency department sepsis patients2012https://doi.org/10.1186/cc11788
Dimensions AIAudit of the ward-based management of severe sepsis in a large teaching hospital2012https://doi.org/10.1186/cc11763
Dimensions AICitrate anticoagulation protocol to treat septic shock patients with liver dysfunction in CPFA extracorporeal therapy2012https://doi.org/10.1186/cc11752
Dimensions AIDevelopment of a point-of-care-testing system for procalcitonin2012https://doi.org/10.1186/cc11776
Dimensions AIEarly fluid therapy with splanchnic sympathetic blockage prevented microcirculation damage, gut bacterial overgrowth, bacterial translocation and mortality in sepsis2012https://doi.org/10.1186/cc11779
Dimensions AIEffects of statins on mitochondrial respiration and outcome during experimental sepsis2012https://doi.org/10.1186/cc11711
Dimensions AIIL-6 and IFN? play a role in fatal cases of 5N1 influenza in children2012https://doi.org/10.1186/cc11740
Dimensions AIImmunological modulation of estrogen during sepsis2012https://doi.org/10.1186/cc11714
Dimensions AIImpact of interventions to reduce device-related infections in Indian cancer centre ICUs2012https://doi.org/10.1186/cc11778
Dimensions AILPS-induced Pellino3 degradation is mediated by p62-dependent autophagy2012https://doi.org/10.1186/cc11737
Dimensions AIManagement of sepsis in Indian ICUs: Indian data from the MOSAICS study2012https://doi.org/10.1186/cc11777
Dimensions AIMannose-binding lectin deficiency and NOD2 mutations do not predispose to Staphylococcus aureus bloodstream infections but may influence outcome2012https://doi.org/10.1186/cc11759
Dimensions AINoradrenergic neurons regulate the egress and trafficking of splenic monocytes and influence mortality during Gram-negative infection in mice2012https://doi.org/10.1186/cc11758
Dimensions AIPancreatic stone protein: a new predictor of outcome in patients with peritonitis2012https://doi.org/10.1186/cc11749
Dimensions AIQuantified temporal changes of heart rate variability when developing SIRS2012https://doi.org/10.1186/cc11796
Dimensions AIRole of TREM-1 in endothelial dysfunction during experimental sepsis2012https://doi.org/10.1186/cc11736
Dimensions AIUse of intravenous and intramuscular immunoglobulin in the practice of treatment for purulent and septic deaths in newborns2012https://doi.org/10.1186/cc11800
EmbaseA Molecular Host Response Assay to Discriminate Between Sepsis and Infection-Negative Systemic Inflammation in Critically Ill Patients: Discovery and Validation in Independent Cohorts.2015https://dx.doi.org/10.1371/journal.pmed.1001916
N.B. These documents automatically identified may not have been verified by the study sponsor.