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suPAR to Guide Antibiotics in Emergency Department

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ClinicalTrials.gov Identifier: NCT03717350
Recruitment Status : Recruiting
First Posted : October 24, 2018
Last Update Posted : February 21, 2019
Sponsor:
Information provided by (Responsible Party):
Hellenic Institute for the Study of Sepsis

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.

Condition or disease Intervention/treatment Phase
Sepsis Drug: Meropenem Drug: Placebo Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 244 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Similar appearance of study drug of both arms
Primary Purpose: Treatment
Official Title: A suPAR Guided Double-blind Randomized Clinical Trial of Initiation of Antibiotics for Presumed Infection at the Emergency Department
Actual Study Start Date : October 27, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics Sepsis
Drug Information available for: Meropenem

Arm Intervention/treatment
Placebo Comparator: Placebo
100ml of sodium chloride 0.9% within 15 minutes intravenously
Drug: Placebo
100ml of sodium chloride 0.9% within 15 minutes intravenously once
Other Name: Diluent

Active Comparator: Antibiotic
2g of meropenem diluted in 100ml of sodium chloride 0.9% within 15 minutes intravenously
Drug: Meropenem
2g of meropenem diluted in 100ml of sodium chloride 0.9% within 15 minutes intravenously administered once
Other Name: Carbapenem




Primary Outcome Measures :
  1. Mortality [ Time Frame: 28 days ]
    Comparative efficacy of the applied intervention on 28-day mortality


Secondary Outcome Measures :
  1. Sepsis mortality [ Time Frame: 28 days ]
    Comparative efficacy of the applied intervention on mortality for patients meeting the Sepsis-3 definition of sepsis

  2. Short-term mortality [ Time Frame: 7 days ]
    Comparative efficacy of the applied intervention on 7-day mortality

  3. Long-term mortality 1 [ Time Frame: 60 days ]
    Comparative efficacy of the applied intervention on 60-day mortality

  4. Long-term mortality 2 [ Time Frame: 90 days ]
    Comparative efficacy of the applied intervention on 90-day mortality

  5. Infection resolution [ Time Frame: 90 days ]
    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.

  6. Change of initial treatment [ Time Frame: 28 days ]
    Comparative efficacy of the applied intervention on the need to change antibiotics

  7. Duration of hospitalization [ Time Frame: 90 days ]
    Comparative efficacy of the applied intervention on the duration of hospitalization

  8. Rate of new infections [ Time Frame: 90 days ]
    Comparative efficacy of the applied intervention on the rate of new infections



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Deny to consent
  2. Patients with 0, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03717350


Contacts
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Contact: Evangelos J Giamarellos-Bourboulis, MD, PhD +306945521800 egiamarel@med.uoa.gr
Contact: Charambos Gogos, MD, PhD +306944799784 egogos@med.upatras.gr

Locations
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Greece
4th Department of Internal Medicine, ATTIKON University Hospital Recruiting
Athens, Attiki, Greece, 12462
Contact: Antonios Papadopoulos, MD, PhD    +306977302400    antpapa1@otenet.gr   
Contact: Evdoxia Kyriazopoulou, MD, PhD    +302105832563    ekyr@med.uoa.gr   
Sub-Investigator: Antonios Papadopoulos, MD, PhD         
Sub-Investigator: Nikolaos Antonakos, MD, PhD         
Sub-Investigator: Maria-Evangelia Adami, MD         
Department of Internal Medicine, Patras University Hospital Recruiting
Patras, Greece
Contact: Charalambos Gogos, MD, PhD    +306944799784    cgogos@med.upatras.gr   
Contact: Karolina Akinosoglou, MD, PhD    ++306977762897    akin@upatras.gr   
Principal Investigator: Charalambos Gogos, MD, PhD         
Sub-Investigator: Karolina Akinosoglou, MD, PhD         
Sub-Investigator: Ann-Liz Delastic, MD, PhD         
Sponsors and Collaborators
Hellenic Institute for the Study of Sepsis
Investigators
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Study Chair: Evangelos Giamarellos-Bourboulis, MD, PhD ATTIKON University Hospital

Publications:
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Responsible Party: Hellenic Institute for the Study of Sepsis
ClinicalTrials.gov Identifier: NCT03717350    
Other Study ID Numbers: SUPERIOR
First Posted: October 24, 2018    Key Record Dates
Last Update Posted: February 21, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hellenic Institute for the Study of Sepsis:
biomarkers
suPAR
outcome
antibiotics
Additional relevant MeSH terms:
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Emergencies
Disease Attributes
Pathologic Processes
Anti-Bacterial Agents
Meropenem
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents