- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03717350
suPAR to Guide Antibiotics in Emergency Department
A suPAR Guided Double-blind Randomized Clinical Trial of Initiation of Antibiotics for Presumed Infection at the Emergency Department
Study Overview
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Unpublished data of the Hellenic Sepsis Study Group (HSSG) suggest that among patients with at least one sign of the qSOFA score, those with suPAR greater than 12 ng/ml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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Athens, Greece, 11527
- Recruiting
- 1st Department of Internal Medicine of G. GENNIMATAS General Hospital
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Contact:
- George Adamis, MD
- Phone Number: 2107768534
- Email: adamismd@otenet.gr
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Athens, Greece, 11527
- Recruiting
- 3rd Department of Internal Medicine at SOTIRIA General Hospital of Chest Diseases of Athens
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Contact:
- Garyfallia Poulakou, MD, PhD
- Phone Number: 2107763400
- Email: gpoulakou@gmail.com
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Athens, Greece, 15126
- Recruiting
- Εmergency Department of Sismanogleion Athens General Hospital
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Contact:
- Vassileios Kaldis, MD
- Phone Number: 2132058 841
- Email: vkaldis@yahoo.gr
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Patras, Greece
- Recruiting
- Department of Internal Medicine, Patras University Hospital
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Contact:
- Charalambos Gogos, MD, PhD
- Phone Number: +306944799784
- Email: cgogos@med.upatras.gr
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Contact:
- Karolina Akinosoglou, MD, PhD
- Phone Number: ++306977762897
- Email: akin@upatras.gr
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Principal Investigator:
- Charalambos Gogos, MD, PhD
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Sub-Investigator:
- Karolina Akinosoglou, MD, PhD
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Sub-Investigator:
- Ann-Liz Delastic, MD, PhD
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Attiki
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Athens, Attiki, Greece, 12462
- Recruiting
- 4th Department of Internal Medicine, Attikon University Hospital
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Contact:
- Antonios Papadopoulos, MD, PhD
- Phone Number: +306977302400
- Email: antpapa1@otenet.gr
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Contact:
- Evdoxia Kyriazopoulou, MD, PhD
- Phone Number: +302105832563
- Email: ekyr@med.uoa.gr
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Sub-Investigator:
- Antonios Papadopoulos, MD, PhD
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Sub-Investigator:
- Nikolaos Antonakos, MD, PhD
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Sub-Investigator:
- Maria-Evangelia Adami, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent provided by the patient or by their legal representative in case of patients unable to consent
- Age equal to or above 18 years
- Male or female gender
- Clinical suspicion of infection
- qSOFA equal to 1 point
- suPAR blood level equal or above 12 ng/ml
Exclusion Criteria:
- Denial to consent
- Patients with 2 or 3 qSOFA signs
- Pregnancy (confirmed by blood or urinary pregnancy test) for female patients of reproductive age
- Organ transplantation
- Fully-blown sepsis with overt failing organs necessitating immediate resuscitation as defined by the attending physicians
- Do not resuscitate decision
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
100ml of sodium chloride 0.9% within 15 minutes intravenously
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100ml of sodium chloride 0.9% within 15 minutes intravenously once
Other Names:
|
Active Comparator: Antibiotic
2g of meropenem diluted in 100ml of sodium chloride 0.9% within 15 minutes intravenously
|
2g of meropenem diluted in 100ml of sodium chloride 0.9% within 15 minutes intravenously administered once
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The efficacy of the applied intervention versus standard practice on the early worsening of the patient.
Time Frame: 1 day (24 hours)
|
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.
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1 day (24 hours)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sepsis mortality
Time Frame: 28 days
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Comparative efficacy of the applied intervention on mortality for patients meeting the Sepsis-3 definition of sepsis
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28 days
|
Short-term mortality
Time Frame: 7 days
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Comparative efficacy of the applied intervention on 7-day mortality
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7 days
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Long-term mortality 1
Time Frame: 60 days
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Comparative efficacy of the applied intervention on 60-day mortality
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60 days
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Long-term mortality 2
Time Frame: 90 days
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Comparative efficacy of the applied intervention on 90-day mortality
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90 days
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Infection resolution
Time Frame: 90 days
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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.
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90 days
|
Change of initial treatment
Time Frame: 28 days
|
Comparative efficacy of the applied intervention on the need to change antibiotics
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28 days
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Duration of hospitalization
Time Frame: 90 days
|
Comparative efficacy of the applied intervention on the duration of hospitalization
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90 days
|
Rate of new infections
Time Frame: 90 days
|
Comparative efficacy of the applied intervention on the rate of new infections
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90 days
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The early worsening of the patient
Time Frame: 1 day (24 hours)
|
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
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1 day (24 hours)
|
Collaborators and Investigators
Investigators
- Study Chair: Evangelos Giamarellos-Bourboulis, MD, PhD, Attikon Hospital
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- SuPERIOR
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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