Clinical trial NCT03306186: Hemospec Device for the Diagnosis of Sepsis
Official title: Integration of Clinical and Laboratory Information to Generate Technological Advance for the Diagnosis of Sepsis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Keywords: diagnosis
prognosis
Lead sponsor: University of Athens
Sponsor class: OTHER
Collaborators: name: Ippokration General Hospital
name: Tzanion General Hospital of Piraeus
name: Aghia Olga Konstantopouleion General Hospital
First posted: 2017-10-10
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: A diagnostic devise, namely HemoSpec, had been developed that integrates clinical information, along with information on circulating protein biomarkers and the morphology of white blood cells to achieve early diagnosis of sepsis. The current study is aiming to validate and improve performance of HemoSpec for the rapid assessment of the critically ill patient.

Detailed description: Sepsis is a life-threating organ dysfunction resulting from the dysregulated response of the host to an infection. It is estimated that 1.5 million people present with sepsis annually in Northern America and another 1.5 million people in Europe; 30 to 50% of them die making sepsis the leading cause of death. The key-point in the management of sepsis is the early resuscitation with broad-spectrum antimicrobials and intravenous fluids, if possible within the first hour. The great mortality of sepsis indicates that this goal is not easy to be achieved for two main reasons: the first is the delay in recognition of the septic patients and the second is the resistance of the implicated pathogen to broad-spectrum antimicrobials.

In an attempt to improve the failure of physicians for early sepsis recognition, several markers have been developed. Some of them rely on clinical signs of the host and others on the measurements of circulating biomarkers. Recently, qSOFA (quick SOFA score) has been introduced to help the early recognition of sepsis in patients who present with infection outside the Intensive care Unit (ICU) i.e. either in the community or during hospitalization in the general ward1. However, there are concerns of the sensitivity of qSOFA and many introduce the need to measure biomarkers in serum. These biomarkers are usually protein molecules that are over-produced in the host as a result of the interaction with an infective insult. However, these protein molecules are produced by white blood cells. What is currently known is that although most of patients present with a similar phenotype, their pathophysiology is diverse. More precisely, although the majority of patients with sepsis present with high concentrations of protein molecules like interleukin (IL)-6, C-reactive protein (CRP) and procalcitonin (PCT) in their blood, in some patients circulating white blood cells remain over-active and in other patients they are significantly anergic, a situation often known as sepsis-induced immunoparalysis. Another molecule, called soluble urokinase plasminogen activator receptor (suPAR), is the shed uPAR receptor on neutrophils and is released in the circulation as a result of neutrophil activation; concentrations greater than 12 ng/ml can trace with negative predictive value almost 95% the patient at great chance of unfavorable outcome. As such, the robust diagnosis of sepsis may rely on a combination of clinical assessment, measurement of protein biomarkers and validation of the activity of circulating white blood cells.

One FrameWork 7-funded initiative from seven European countries aims to develop a rapid score that can integrate all clinical and laboratory information and provide early diagnosis whether a patient has sepsis or not. The vision of this initiative is to build a device that is called HemoSpec. With this approach, whole blood coming from patients will be in parallel analyzed into three aspects: a) absolute white blood cell counting; b) information on the fluidity and activity of the white blood cells using Raman spectroscopy; and c) measurement of serum levels of IL-6, CRP, PCT and suPAR. The end result is building a diagnostic algorithm where clinical information is also taken into consideration.

The project was started in November 2013 and the HemoSpec device is anticipated to be ready by February 2017. The diagnostic performance of HemoSpec is currently based on preliminary data coming from 60 patients (20 controls, 20 with systemic inflammatory response syndrome and 20 with sepsis) hospitalized in Jena University Hospital. The current study is aiming to validate and improve performance of HemoSpec for the rapid assessment of the critically ill patient in a larger phase II diagnostic study.

Eligibility criteria: Inclusion Criteria:

* Age above or equal to 18 years old
* Both genders
* Written consent provided from patients or their first-degree relatives for patients unable to consent
* Patients with acute pancreatitis or post-operative or with clinical signs of infection
* Considerable risk of death as as indicated by the presence of at least one of the following: i) sudden alteration of mental status; ii) systolic blood pressure less than 100 mmHg; and iii) high respiratory rate defined as more than or equal to 22 breaths per minute.

Exclusion Criteria:

* Known infection by the human immunodeficiency virus-1;
* Neutropenia defined as an absolute neutrophil count lower than 1000 neutrophils/mm3 due to reasons other than an infection.
* Single trauma or multiple injuries

Primary outcomes:
measure: Sensitivity of HemoSpec for the diagnosis of sepsis
timeFrame: 3 days
Secondary outcomes:
measure: Diagnostic performance for sepsis
timeFrame: 3 days
measure: Prognostics performance for sepsis
timeFrame: 28 days
measure: Prognostic performance for organ dysfunction
timeFrame: 28 days
measure: Diagnostic performance over qSOFA
timeFrame: 3 days
measure: Diagnostic performance and microbiology
timeFrame: 3 days
Other outcomes:
Locations:
city: Athens
country: Greece
facility: 1st Department of Propedeutic Surgery, Ippokration General Hospital
city: Athens
country: Greece
facility: Intensive Care Unit, Ippokration General Hospital
city: Athens
country: Greece
facility: 4th Department of Internal Medicine, ATTIKON University Hospital
city: Athens
country: Greece
facility: Intensive Care Unit, Aghia Olga Konstantopouleion General Hospital
city: Piraeus
country: Greece
facility: Intensive Care Unit, Tzanio Hospital of Piraeus
Study officials:
affiliation: National and Kapodistrian University of Athens
name: Evangelos J Giamarellos-Bourboulis, MD, PhD
role: STUDY_CHAIR
affiliation: National and Kapodistrian University of Athens
name: Konstantinos Toutouzas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tzaneion General Hospital
name: Athanasios Prekates, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ippokration General Hospital
name: Stylianos Karatzas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aghia Olga General Hospital
name: Christos Mathas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
citation: Becker KL, Snider R, Nylen ES. Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations. Crit Care Med. 2008 Mar;36(3):941-52. doi: 10.1097/CCM.0B013E318165BABB.
citation: Giamarellos-Bourboulis EJ, Norrby-Teglund A, Mylona V, Savva A, Tsangaris I, Dimopoulou I, Mouktaroudi M, Raftogiannis M, Georgitsi M, Linner A, Adamis G, Antonopoulou A, Apostolidou E, Chrisofos M, Katsenos C, Koutelidakis I, Kotzampassi K, Koratzanis G, Koupetori M, Kritselis I, Lymberopoulou K, Mandragos K, Marioli A, Sunden-Cullberg J, Mega A, Prekates A, Routsi C, Gogos C, Treutiger CJ, Armaganidis A, Dimopoulos G. Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor. Crit Care. 2012 Aug 8;16(4):R149. doi: 10.1186/cc11463.