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 : July 30, 2020
|Condition or disease||Intervention/treatment||Phase|
|Sepsis||Drug: Meropenem Drug: Placebo||Phase 2 Phase 3|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||220 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Similar appearance of study drug of both arms|
|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 :||July 31, 2021|
|Estimated Study Completion Date :||August 31, 2021|
Placebo Comparator: Placebo
100ml of sodium chloride 0.9% within 15 minutes intravenously
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
2g of meropenem diluted in 100ml of sodium chloride 0.9% within 15 minutes intravenously administered once
Other Name: Carbapenem
- 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.
- Sepsis mortality [ Time Frame: 28 days ]Comparative efficacy of the applied intervention on mortality for patients meeting the Sepsis-3 definition of sepsis
- Short-term mortality [ Time Frame: 7 days ]Comparative efficacy of the applied intervention on 7-day mortality
- Long-term mortality 1 [ Time Frame: 60 days ]Comparative efficacy of the applied intervention on 60-day mortality
- Long-term mortality 2 [ Time Frame: 90 days ]Comparative efficacy of the applied intervention on 90-day mortality
- 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.
- Change of initial treatment [ Time Frame: 28 days ]Comparative efficacy of the applied intervention on the need to change antibiotics
- Duration of hospitalization [ Time Frame: 90 days ]Comparative efficacy of the applied intervention on the duration of hospitalization
- Rate of new infections [ Time Frame: 90 days ]Comparative efficacy of the applied intervention on the rate of new infections
- 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
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
|Contact: Evangelos J Giamarellos-Bourboulis, MD, PhDfirstname.lastname@example.org|
|Contact: Charambos Gogos, MD, PhDemail@example.com|
|4th Department of Internal Medicine, ATTIKON University Hospital||Recruiting|
|Athens, Attiki, Greece, 12462|
|Contact: Antonios Papadopoulos, MD, PhD +306977302400 firstname.lastname@example.org|
|Contact: Evdoxia Kyriazopoulou, MD, PhD +302105832563 email@example.com|
|Sub-Investigator: Antonios Papadopoulos, MD, PhD|
|Sub-Investigator: Nikolaos Antonakos, MD, PhD|
|Sub-Investigator: Maria-Evangelia Adami, MD|
|1st Department of Internal Medicine of G. GENNIMATAS General Hospital||Recruiting|
|Athens, Greece, 11527|
|Contact: George Adamis, MD 2107768534 firstname.lastname@example.org|
|3rd Department of Internal Medicine at SOTIRIA General Hospital of Chest Diseases of Athens||Recruiting|
|Athens, Greece, 11527|
|Contact: Garyfallia Poulakou, MD, PhD 2107763400 email@example.com|
|Εmergency Department of Sismanogleion Athens General Hospital||Recruiting|
|Athens, Greece, 15126|
|Contact: Vassileios Kaldis, MD 2132058 841 firstname.lastname@example.org|
|Department of Internal Medicine, Patras University Hospital||Recruiting|
|Contact: Charalambos Gogos, MD, PhD +306944799784 email@example.com|
|Contact: Karolina Akinosoglou, MD, PhD ++306977762897 firstname.lastname@example.org|
|Principal Investigator: Charalambos Gogos, MD, PhD|
|Sub-Investigator: Karolina Akinosoglou, MD, PhD|
|Sub-Investigator: Ann-Liz Delastic, MD, PhD|
|Study Chair:||Evangelos Giamarellos-Bourboulis, MD, PhD||Attikon Hospital|