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Trial registered on ANZCTR


Registration number
ACTRN12617000429358
Ethics application status
Approved
Date submitted
27/01/2017
Date registered
24/03/2017
Date last updated
22/11/2019
Date data sharing statement initially provided
22/11/2019
Date results information initially provided
22/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Evaluation of the presence and the prognostic role of endogenous autoantibodies and circulating mediators in the blood of patients with sepsis and septic shock defined on the basis of the recently published new criteria.
Scientific title
Evaluation of the presence and the prognostic role of endogenous autoantibodies and circulating mediators in the blood of patients with sepsis and septic shock defined on the basis of the recently published new criteria.
Secondary ID [1] 291002 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Autoimmunity and sepsis
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis 301772 0
Condition category
Condition code
Infection 301462 301462 0 0
Studies of infection and infectious agents
Inflammatory and Immune System 301463 301463 0 0
Autoimmune diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients will be divided into three groups according to the diagnosis: 1) infection with quick SOFA<2, 2) sepsis, and 3)septic shock, according to the new definitions (Singer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:801-10).
The definition of sepsis will be given according to an increase in SOFA equal or greater than 2; while the definition of septic shock will require the use of vasopressors to maintain a mean arterial pressure of 65 mmHg or greater and the presence of serum lactate level greater than 2 mmol/L in the absence of hypovolemia. We will enroll prospectively the first 200 patients meeting the three diagnostic groups that enter the Emergency Department of the Maggiore della Carita Hospital in Novara (this estimate will be refined on the basis of a pilot study). We will also study a group of 30 healthy volunteers matched for gender and age.
With this study we aim to demonstrate the presence and the prognostic role of endogenous autoantibodies and circulating mediators in the blood of the three groups of patients studied and in a group of controls.
Data and samples (blood and urine) collection will be carried out at enrollment (T0), after 24 hours (T1), after 48 hours (T2) and after 7 days from the enrollment or at discharge (T3). We will also perform a telephonic follow-up 1 and 6 months after the enrollment in order to assess mortality.
Protein assays will be performed by using Enzyme-Linked Immunosorbent Assay (ELISA) in order to evaluate the blood or urine concentration of OPN and anti-OPN antibodies, IL-8 and anti-IL-8 IgM, , IL-6 and anti-IL-6, GAS6 and sMer, suPAR, NGAL and KIM1.
Isolation and characterization of primary cultures of human kidney-derived endothelial cells will be carried out using typical endothelial markers (CD31, CD105, and von Willebrand factor). Plasma collected from septic patients will be incubated on these cells for specific in vitro assays: angiogenetic, apoptotic, quantification of nitric oxide (NO) generation and radical oxygen species (ROS) production assay.
Intervention code [1] 296966 0
Not applicable
Comparator / control treatment
We will also study a group of 30 healthy volunteers matched for gender and age. Blood and urine from healthy volunteers will be used in the experimental study in vitro as control samples.
Control group
Active

Outcomes
Primary outcome [1] 300875 0
With this study we aim to demonstrate (as composite outcome) the presence and the prognostic role of endogenous autoantibodies and circulating mediators in the blood and urine of patients with 1) infection but quick SOFA<2; 2) sepsis and 3) septic shock defined on the basis of the recently published new criteria.
We will measure in blood and urine the concentration of OPN and anti-OPN antibodies, IL-8 and anti-IL-8 IgM, IL-6 and anti-IL-6, GAS6 and sMer, suPAR, NGAL and KIM1.
Timepoint [1] 300875 0
Data and samples collection will be carried out at enrollment (T0), after 24 hours (T1), after 48 hours (T2) and after 7 days from the enrollment or at discharge (T3). We will also perform a telephonic follow-up 1 and 6 months after the enrollment in order to assess mortality.
Primary outcome [2] 300876 0
We will evaluate the ability of the different biomarkers in blood and urine (i.e.,OPN and anti-OPN antibodies, IL-8 and anti-IL-8 IgM, IL-6 and anti-IL-6, GAS6 and sMer, suPAR, NGAL and KIM1). to predict mortality at 1 and 6 months . Mortality will be assessed by looking at the medical records and by phone call,
Timepoint [2] 300876 0
Mortality will be assessed at 1 and 6 months post enrolment.
Secondary outcome [1] 331083 0
We plan to study the specific role of these mediators and autoantibodies on endothelial cell injury through a set of experimental studies in vitro.
Timepoint [1] 331083 0
6 months

Eligibility
Key inclusion criteria
Inclusion criteria will be: suspected infection with at least two of the elements of the quick Sequential Organ Failure Assessment score (qSOFA)i.e., respiratory rate equal or more than 22/min, altered mental state with GCS less than 15, systolic arterial blood pressure equal or less than 100 mmHg. A written informed consent and age equal or more than 18 years and less than 85 years old will be mandatory as well. Healthy volunteers will be included if with an age equal or more than 18 years and less than 85 years old.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Age equal or more than 18 years; age less than 85; lack of informed consent.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
In order to perform our statistical analysis, patients will be divided into three groups (infection with quick SOFA less than 2, sepsis and septic shock) according to the diagnosis made by clinicians at the end of the study period. We will compute positive and negative predictive value for sepsis and septic shock of each biomarker and their ability in predicting 1 and 6-month mortality. We will also evaluate the survival during the 6-month follow-up period with Kaplan-Meier curves.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
1/10/2016
Date of last participant enrolment
Anticipated
30/12/2017
Actual
30/12/2017
Date of last data collection
Anticipated
1/06/2018
Actual
10/07/2018
Sample size
Target
200
Accrual to date
Final
118
Recruitment outside Australia
Country [1] 8607 0
Italy
State/province [1] 8607 0
Novara

Funding & Sponsors
Funding source category [1] 295428 0
University
Name [1] 295428 0
University of Piemonte Orientale "Amedeo Avogadro"
Country [1] 295428 0
Italy
Primary sponsor type
University
Name
University of Piemonte Oreintale "Amedeo Avogadro"
Address
University of Piemonte Oreintale "Amedeo Avogadro"
Via Solaroli 17
28100 Novara
(Italy)
Country
Italy
Secondary sponsor category [1] 294248 0
None
Name [1] 294248 0
None
Address [1] 294248 0
None
Country [1] 294248 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296760 0
Comitato Etico interaziendale di Novara
Ethics committee address [1] 296760 0
Corso Mazzini n. 18
28100 Novara
Ethics committee country [1] 296760 0
Italy
Date submitted for ethics approval [1] 296760 0
20/05/2016
Approval date [1] 296760 0
29/07/2016
Ethics approval number [1] 296760 0

Summary
Brief summary
BACKGROUND: Sepsis represents an acute condition with high mortality.
Endogenous anti-cytokine autoantibodies are present in healthy subjects and in a number of chronic inflammatory diseases. In autoimmune diseases, their role is detrimental as they cause dysfunction and worsen the illness. Their presence and role is sepsis is still not known.
AIM OF THE STUDY: With this study we aim to demonstrate the presence and the prognostic role of autoantibodies and circulating mediators in the blood and urine of patients with sepsis and septic shock defined on the basis of the recently published new criteria.
Trial website
Not applicable
Trial related presentations / publications
Not applicable
Public notes
Not applicable

Contacts
Principal investigator
Name 71978 0
Prof Paolo Navalesi
Address 71978 0
Universita degli Studi "Magna Graecia"di CATANZARO,
Viale Europa - Loc. Germaneto (88100) CATANZARO
Country 71978 0
Italy
Phone 71978 0
+39335 5321910
Fax 71978 0
Email 71978 0
[email protected]
Contact person for public queries
Name 71979 0
Paolo Navalesi
Address 71979 0
Universita degli Studi "Magna Graecia"di CATANZARO,
Viale Europa - Loc. Germaneto (88100) CATANZARO
Country 71979 0
Italy
Phone 71979 0
+39335 5321910
Fax 71979 0
Email 71979 0
[email protected]
Contact person for scientific queries
Name 71980 0
Paolo Navalesi
Address 71980 0
Universita degli Studi "Magna Graecia"di CATANZARO,
Viale Europa - Loc. Germaneto (88100) CATANZARO
Country 71980 0
Italy
Phone 71980 0
+39335 5321910
Fax 71980 0
Email 71980 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not written in the protocol submitted to the EC.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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