ANZCTR - Registration

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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

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1115-4269

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Severe sepsis and septic shock

Condition category

Condition code

Inflammatory and Immune System

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]

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]

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]

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]

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]

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]

Development of a machine learning algorithm to predict sepsis status using sepsis gene expression biomarker signatures, clinical progression measures and survival outcomes.

Timepoint [2]

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]

Expansion of the sepsis algorithm to incorporate therapeutic regimens.

Timepoint [3]

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?

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)

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

AusIndustry

Address [1]

Department of Innovation, Industry, Science and Research
Level 12, Creek Street
Brisbane Qld 4000

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

ImmuneXpress Pty Ltd

Address

PO Box 1448
Toowong Qld 4066

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Mater Health Services Human Research Ethics Committee

Ethics committee address [1]

Room 235 Aubigny Place
Mater Misericordiae Health Services
Raymond Tce
South Brisbane Queensland 4101

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/06/2009

Approval date [1]

21/10/2009

Ethics approval number [1]

1400A

Ethics committee name [2]

Royal Brisbane & Women's Hospital Human Research Ethics Committee

Ethics committee address [2]

Herston Road 
Herston Queensland 4029

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

23/09/2009

Approval date [2]

21/11/2009

Ethics approval number [2]

HREC/09/QRBW/295

Ethics committee name [3]

Metro South Human Research Ethics Committee

Ethics committee address [3]

Princess Alexandra Hospital, Ipswich Road Woollongabba Q 4102

Ethics committee country [3]

Australia

Date submitted for ethics approval [3]

01/11/2010

Approval date [3]

04/02/2011

Ethics approval number [3]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

Dr Roslyn Brandon

Address

1100 Dexter Avenue North, Suite 100
Seattle WA, 98109

Country

United States of America

Phone

+1 206 351 2662

Fax

+1 206 273 7401

roz.b@immunexpress.com

Contact person for scientific queries

Name

Dr Allison Sutherland

Address

PO Box 1448, Toowong Q 4066

Country

Australia

Phone

+61 423 684 659

Fax

+617 3870 9101

allison.s@immunexpress.com

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

Source	Title	Year of Publication	DOI
Dimensions AI	A standardized protocol for the multiplex PCR technique Septifast® Roche for neonatal samples with suspected sepsis	2012	https://doi.org/10.1186/cc11766
Dimensions AI	Advance directives and end-of-life decision-making in the ICU: results from an observational study	2012	https://doi.org/10.1186/cc11695
Dimensions AI	AMP-activated protein kinase preserves endothelial tight junctions in the coronary microcirculation during sepsis	2012	https://doi.org/10.1186/cc11717
Dimensions AI	Assessment of clinical deterioration and progressive organ failure in moderate-severity emergency department sepsis patients	2012	https://doi.org/10.1186/cc11788
Dimensions AI	Audit of the ward-based management of severe sepsis in a large teaching hospital	2012	https://doi.org/10.1186/cc11763
Dimensions AI	Citrate anticoagulation protocol to treat septic shock patients with liver dysfunction in CPFA extracorporeal therapy	2012	https://doi.org/10.1186/cc11752
Dimensions AI	Development of a point-of-care-testing system for procalcitonin	2012	https://doi.org/10.1186/cc11776
Dimensions AI	Early fluid therapy with splanchnic sympathetic blockage prevented microcirculation damage, gut bacterial overgrowth, bacterial translocation and mortality in sepsis	2012	https://doi.org/10.1186/cc11779
Dimensions AI	Effects of statins on mitochondrial respiration and outcome during experimental sepsis	2012	https://doi.org/10.1186/cc11711
Dimensions AI	IL-6 and IFN? play a role in fatal cases of 5N1 influenza in children	2012	https://doi.org/10.1186/cc11740
Dimensions AI	Immunological modulation of estrogen during sepsis	2012	https://doi.org/10.1186/cc11714
Dimensions AI	Impact of interventions to reduce device-related infections in Indian cancer centre ICUs	2012	https://doi.org/10.1186/cc11778
Dimensions AI	LPS-induced Pellino3 degradation is mediated by p62-dependent autophagy	2012	https://doi.org/10.1186/cc11737
Dimensions AI	Management of sepsis in Indian ICUs: Indian data from the MOSAICS study	2012	https://doi.org/10.1186/cc11777
Dimensions AI	Mannose-binding lectin deficiency and NOD2 mutations do not predispose to Staphylococcus aureus bloodstream infections but may influence outcome	2012	https://doi.org/10.1186/cc11759
Dimensions AI	Noradrenergic neurons regulate the egress and trafficking of splenic monocytes and influence mortality during Gram-negative infection in mice	2012	https://doi.org/10.1186/cc11758
Dimensions AI	Pancreatic stone protein: a new predictor of outcome in patients with peritonitis	2012	https://doi.org/10.1186/cc11749
Dimensions AI	Quantified temporal changes of heart rate variability when developing SIRS	2012	https://doi.org/10.1186/cc11796
Dimensions AI	Role of TREM-1 in endothelial dysfunction during experimental sepsis	2012	https://doi.org/10.1186/cc11736
Dimensions AI	Use of intravenous and intramuscular immunoglobulin in the practice of treatment for purulent and septic deaths in newborns	2012	https://doi.org/10.1186/cc11800
Embase	A Molecular Host Response Assay to Discriminate Between Sepsis and Infection-Negative Systemic Inflammation in Critically Ill Patients: Discovery and Validation in Independent Cohorts.	2015	https://dx.doi.org/10.1371/journal.pmed.1001916

N.B. These documents automatically identified may not have been verified by the study sponsor.

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