suPAR to Guide Antibiotics in Emergency Department

NCT ID: NCT03717350

Last Updated: 2020-07-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-27
• Study Completion Date: 2021-08-31

Brief Summary

The aim of the current study is to evaluate suPAR - guided medical intervention, consisting of early antibiotic administration at the emergency room for presumed infection and sepsis and evaluate the impact of this intervention to the patients' final outcome. Since the traditionally used biomarkers (PCT, CRP) and scores (SOFA score) for early recognition of severity of infection fail to achieve maximum accuracy in all cases, suPAR levels are assessed as a probably better prognostic rule for early recognition of severe infections. The primary study endpoint will be the comparative efficacy of the early suPAR-guided administration of antibiotics versus standard practice on 28-day mortality.

Detailed Description

Sepsis is among the leading causes of death worldwide. It is well-perceived that early recognition of sepsis is the mainstay of treatment. Recently it has been proposed that the quick sequential organ fialure assessment (qSOFA) score can be used as a screening tool in the emergency department (ED) to triage patients with high-risk of death; patients scoring positive at least two of the three signs of qSOFA are at a high-risk for death. However, this is challenged since it may be the case that the risk of death is high even among patients with only one sign of qSOFA.

Soluble urokinase plasminogen activator receptor (suPAR), the soluble form of the membrane bound receptor (uPAR), is a recently known glycoprotein involved in inflammation. uPAR is expressed on various immune cells (neutrophils, lymphocytes, monocytes, macrophages) and is cleaved from their surface after an inflammatory stimuli to enhance chemotaxis and cell migration. Increased suPAR blood levels mirror the degree of activation of the immune system by different antigenic stimuli including diverse neoplastic and infectious agents and other inflammation-mediated diseases. SuPAR levels generally correlate to the severity of the disease.

It has been shown that suPAR blood levels have low diagnostic value (cannot discriminate between bacterial, viral or parasitic infection, Gram (+) or Gram (-) bacteraemia. However, they present superior prognostic value as compared with single parameters of inflammation and organ dysfunction (like C-reactive protein (CRP) and procalcitonin (PCT) in critically ill patients, and suPAR's prognostic value of death is even more enhanced when combined to other biomarkers and physiological scores (e.g. Acute Physiology and Chronic Health Evaluation-APACHE II).

Why choose suPAR as biomarker at emergency basis? Because, in contrast to many pro-inflammatory cytokines, suPAR exhibits favorable properties due to its high stability in serum samples and limited circadian changes in plasma concentrations. It also constitutes a serum/plasma biomarker that is easily performed on-site and provides information within one hour after sampling21, 22.

Unpublished data of the Hellenic Sepsis Study Group (HSSG) suggest that among patients with at least one sign of the qSOFA score, those with suPAR greater than 12 ng/ml are at a substantial risk for death with mortality exceeding 30%. To this end, patients with suspicion for an infection and with qSOFA 1 and suPAR greater than 12 ng/ml constitute a group of patients requiring early intervention.

The aim of the current study is to evaluate suPAR - guided medical intervention, consisting of early antibiotics' administration at the emergency room for presumed infection and sepsis and evaluate the impact of this intervention to the patients' final outcome.

Conditions

Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

100ml of sodium chloride 0.9% within 15 minutes intravenously

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

100ml of sodium chloride 0.9% within 15 minutes intravenously once

Antibiotic

2g of meropenem diluted in 100ml of sodium chloride 0.9% within 15 minutes intravenously

Group Type: ACTIVE_COMPARATOR

Meropenem

Intervention Type: DRUG

2g of meropenem diluted in 100ml of sodium chloride 0.9% within 15 minutes intravenously administered once

Interventions

Meropenem

2g of meropenem diluted in 100ml of sodium chloride 0.9% within 15 minutes intravenously administered once

Intervention Type: DRUG

Placebo

100ml of sodium chloride 0.9% within 15 minutes intravenously once

Intervention Type: DRUG

Other Intervention Names

Carbapenem; Diluent

Eligibility Criteria

Inclusion Criteria

1. Written informed consent provided by the patient or by their legal representative in case of patients unable to consent

2. Age equal to or above 18 years

3. Male or female gender

4. Clinical suspicion of infection

5. qSOFA equal to 1 point

6. suPAR blood level equal or above 12 ng/ml

Exclusion Criteria

1. Denial to consent

2. Patients with 2 or 3 qSOFA signs

3. Pregnancy (confirmed by blood or urinary pregnancy test) for female patients of reproductive age

4. Organ transplantation

5. Fully-blown sepsis with overt failing organs necessitating immediate resuscitation as defined by the attending physicians

6. Do not resuscitate decision

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hellenic Institute for the Study of Sepsis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Evangelos Giamarellos-Bourboulis, MD, PhD

Role: STUDY_CHAIR

Attikon Hospital

Locations

4th Department of Internal Medicine, ATTIKON University Hospital

Athens, Attica, Greece

Site Status: RECRUITING

1st Department of Internal Medicine of G. GENNIMATAS General Hospital

Athens, , Greece

Site Status: RECRUITING

3rd Department of Internal Medicine at SOTIRIA General Hospital of Chest Diseases of Athens

Athens, , Greece

Site Status: RECRUITING

Εmergency Department of Sismanogleion Athens General Hospital

Athens, , Greece

Site Status: RECRUITING

Department of Internal Medicine, Patras University Hospital

Pátrai, , Greece

Site Status: RECRUITING

Countries

Greece

Central Contacts

Evangelos J Giamarellos-Bourboulis, MD, PhD

Role: CONTACT

egiamarel@med.uoa.gr

+306945521800

Charambos Gogos, MD, PhD

Role: CONTACT

egogos@med.upatras.gr

+306944799784

Facility Contacts

Antonios Papadopoulos, MD, PhD

Role: primary

antpapa1@otenet.gr

+306977302400

Evdoxia Kyriazopoulou, MD, PhD

Role: backup

ekyr@med.uoa.gr

+302105832563

George Adamis, MD

Role: primary

adamismd@otenet.gr

2107768534

Garyfallia Poulakou, MD, PhD

Role: primary

gpoulakou@gmail.com

2107763400

Vassileios Kaldis, MD

Role: primary

vkaldis@yahoo.gr

2132058 841

Charalambos Gogos, MD, PhD

Role: primary

cgogos@med.upatras.gr

+306944799784

Karolina Akinosoglou, MD, PhD

Role: backup

akin@upatras.gr

++306977762897

References

Giamarellos-Bourboulis EJ, Tsaganos T, Tsangaris I, Lada M, Routsi C, Sinapidis D, Koupetori M, Bristianou M, Adamis G, Mandragos K, Dalekos GN, Kritselis I, Giannikopoulos G, Koutelidakis I, Pavlaki M, Antoniadou E, Vlachogiannis G, Koulouras V, Prekates A, Dimopoulos G, Koutsoukou A, Pnevmatikos I, Ioakeimidou A, Kotanidou A, Orfanos SE, Armaganidis A, Gogos C; Hellenic Sepsis Study Group. Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification. Clin Microbiol Infect. 2017 Feb;23(2):104-109. doi: 10.1016/j.cmi.2016.11.003. Epub 2016 Nov 14.

Reference Type: BACKGROUND

PMID: 27856268 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22873681 (View on PubMed)

Adami ME, Kotsaki A, Antonakos N, Giannitsioti E, Chalvatzis S, Saridaki M, Avgoustou C, Akinosoglou K, Dakou K, Damoraki G, Katrini K, Koufargyris P, Lekakis V, Panagaki A, Safarika A, Eugen-Olsen J, Giamarellos-Bourboulis EJ. qSOFA combined with suPAR for early risk detection and guidance of antibiotic treatment in the emergency department: a randomized controlled trial. Crit Care. 2024 Feb 6;28(1):42. doi: 10.1186/s13054-024-04825-2.

Reference Type: DERIVED

PMID: 38321472 (View on PubMed)

Kyriazopoulou E, Poulakou G, Giamarellos-Bourboulis EJ. Biomarkers in sepsis: can they help improve patient outcome? Curr Opin Infect Dis. 2021 Apr 1;34(2):126-134. doi: 10.1097/QCO.0000000000000707.

Reference Type: DERIVED

PMID: 33534419 (View on PubMed)

Other Identifiers

SUPERIOR

Identifier Type: -

Identifier Source: org_study_id