Clinical trial NCT03717350: suPAR to Guide Antibiotics in Emergency Department
Official title: A suPAR Guided Double-blind Randomized Clinical Trial of Initiation of Antibiotics for Presumed Infection at the Emergency Department
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Sepsis
Keywords: biomarkers
suPAR
outcome
antibiotics
Lead sponsor: Hellenic Institute for the Study of Sepsis
Sponsor class: OTHER
First posted: 2018-10-24
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The efficacy of the applied intervention versus standard practice on the early worsening of the patient.
timeFrame: 1 day (24 hours)
Secondary outcomes:
measure: Sepsis mortality
timeFrame: 28 days
measure: Short-term mortality
timeFrame: 7 days
measure: Long-term mortality 1
timeFrame: 60 days
measure: Long-term mortality 2
timeFrame: 90 days
measure: Infection resolution
timeFrame: 90 days
measure: Change of initial treatment
timeFrame: 28 days
measure: Duration of hospitalization
timeFrame: 90 days
measure: Rate of new infections
timeFrame: 90 days
measure: The early worsening of the patient
timeFrame: 1 day (24 hours)
Other outcomes:
Locations:
city: Athens
country: Greece
facility: 4th Department of Internal Medicine, ATTIKON University Hospital
state: Attiki
city: Athens
country: Greece
facility: 1st Department of Internal Medicine of G. GENNIMATAS General Hospital
city: Athens
country: Greece
facility: 3rd Department of Internal Medicine at SOTIRIA General Hospital of Chest Diseases of Athens
city: Athens
country: Greece
facility: Εmergency Department of Sismanogleion Athens General Hospital
city: Patras
country: Greece
facility: Department of Internal Medicine, Patras University Hospital
Study officials:
affiliation: Attikon Hospital
name: Evangelos Giamarellos-Bourboulis, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
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.
citation: 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.