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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03717350
Other study ID # SUPERIOR
Secondary ID
Status Recruiting
Phase Phase 2/Phase 3
First received
Last updated
Start date October 27, 2018
Est. completion date August 31, 2021

Study information

Verified date July 2020
Source Hellenic Institute for the Study of Sepsis
Contact Evangelos J Giamarellos-Bourboulis, MD, PhD
Phone +306945521800
Email egiamarel@med.uoa.gr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 220
Est. completion date August 31, 2021
Est. primary completion date July 31, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Greece ?mergency Department of Sismanogleion Athens General Hospital Athens
Greece 1st Department of Internal Medicine of G. GENNIMATAS General Hospital Athens
Greece 3rd Department of Internal Medicine at SOTIRIA General Hospital of Chest Diseases of Athens Athens
Greece 4th Department of Internal Medicine, ATTIKON University Hospital Athens Attiki
Greece Department of Internal Medicine, Patras University Hospital Patras

Sponsors (1)

Lead Sponsor Collaborator
Hellenic Institute for the Study of Sepsis

Country where clinical trial is conducted

Greece, 

References & Publications (2)

Giamarellos-Bourboulis EJ, Norrby-Teglund A, Mylona V, Savva A, Tsangaris I, Dimopoulou I, Mouktaroudi M, Raftogiannis M, Georgitsi M, Linnér 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, Sundén-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. — View 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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary The efficacy of the applied intervention versus standard practice on the early worsening of the patient. The primary study endpoint will be the comparative efficacy of the applied intervention (meropenem versus standard practice on the early worsening of the patient. This is defined as any at least one point increase of the admission total SOFA score the first 24 hours. 1 day (24 hours)
Secondary Sepsis mortality Comparative efficacy of the applied intervention on mortality for patients meeting the Sepsis-3 definition of sepsis 28 days
Secondary Short-term mortality Comparative efficacy of the applied intervention on 7-day mortality 7 days
Secondary Long-term mortality 1 Comparative efficacy of the applied intervention on 60-day mortality 60 days
Secondary Long-term mortality 2 Comparative efficacy of the applied intervention on 90-day mortality 90 days
Secondary Infection resolution Effect of the intervention on the time to infection resolution. This time point is limited for patients who will eventually be diagnosed of a specific infectious diseases making them eligible for the study and it is defined as the time point when all clinical signs of the infection are cleared. 90 days
Secondary Change of initial treatment Comparative efficacy of the applied intervention on the need to change antibiotics 28 days
Secondary Duration of hospitalization Comparative efficacy of the applied intervention on the duration of hospitalization 90 days
Secondary Rate of new infections Comparative efficacy of the applied intervention on the rate of new infections 90 days
Secondary The early worsening of the patient The early worsening of the patient defined as for the primary endpoint but analyzed separately per quartile of the total SOFA score of the patient population 1 day (24 hours)
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