Fast Assay for Pathogen Identification and Characterization

NCT03841162 | Completed

• 1 other identifier: 18.106/infect18.03
• Study Type: observational
• Target: 1,957
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is a life-threatening disease caused by a dysregulated host response to infection. This can lead to organ-dysfunction and septic shock, which is a subset of sepsis where underlying abnormalities increase mortality remarkably. Blood cultures are the gold standard for identifying pathogens in the bloodstream (bacteremia). It is based on cultivation techniques which, theoretically, can detect a single pathogenic cell from a patient sample. However, blood cultures have serious limitations, such as long time to result (3-7 days). This leads to the fact that only a small fraction of the patients obtain a correct diagnosis and in further consequence get the optimal antimicrobial treatment. Patients with sepsis should get antimicrobial treatment within the hour. Thus, physicians start treatment empirically, with broad-spectrum antibiotics. This puts a selective pressure on pathogens and has led to an increased amount of antibiotic resistance. Faster diagnostics are necessary to ensure an immediate and targeted treatment. In the EU-funded FAPIC project, two diagnostic systems that can be used with direct sample material from patients will be developed, avoiding the time-consuming cultivation of pathogens. In this study, the evaluation of the rapid diagnostics will be performed in patients with sepsis, suspected of bacteremia. To this aim, the performance of the diagnostic systems will be evaluated using blood samples that are collected in parallel with blood cultures. In addition, clinical data of the patients will be collected. In routine care, two blood culture sets (2x2 bottles) per patient are collected. One extra blood samples (EDTA, 9 ml) will be sampled with each blood culture set, totaling 2 samples per patient. In this study, patients presenting at the Emergency Department (ED), and the department of infectious diseases/nephrology will be included. The results will be used to estimate the performance, sensitivity, and specificity of the diagnostic systems compared to blood culture. Furthermore, in order to determine the severity of sepsis and to describe the patient population, clinically relevant parameters and laboratory parameters (ferritin, HLA-DR, serum lactate, SOFA score) will be assessed to determine its association with severity of disease and patient mortality. Evaluation will be done exclusively in the lab, and will not be used directly for the diagnosis or management of patients. Standard care will still be provided.

Conditions

Bacteremia; Sepsis; Septic Shock

Keywords

Blood Cultures

Outcome Measures

Primary Outcomes (4)

• Confirmed bacteremia based on positive blood cultures (SOFA score)

  Differences in SOFA score between patients with positive blood cultures and patients with negative blood cultures. SOFA: Sequential Organ Failure Assessment; Range 0-4 (better to worse).

  7 days

• Confirmed bacteremia based on positive blood cultures (Serum Lactate)

  Differences in Serum Lactate levels between patients with positive blood cultures and patients with negative blood cultures

  7 days

• Confirmed bacteremia based on positive blood cultures (Ferritin)

  Differences in Ferritin levels between patients with positive blood cultures and patients with negative blood cultures

  7 days

• Test performance

  Performance characteristics (Clinical sensitivity, specificity and accuracy) of a new rapid diagnostic systems

  1 year

Secondary Outcomes (6)

• Length of Stay (SOFA score)

  1 year

• Length of Stay (Serum Lactate)

  1 year

• Length of Stay (Ferritin)

  1 year

• 30-day Mortality (Sofa score)

  30 days

• 30-day Mortality (Serum Lactate)

  30 days

Study Arms (1)

Patients with suspected sepsis

Patients for whom blood cultures are drawn at the Emergency Department or the department of Infectious Diseases/Nephrology

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with suspected sepsis, for whom blood cultures are drawn.

You may qualify if:

• Patients for whom blood cultures are drawn
• Age ≥ 18

You may not qualify if:

• Age \< 18
• Patients who are not hospitalized and sent home after ED admission
• Patients from the haematology department
• Duplicate blood cultures from the same bacteraemia episode (blood cultures drawn \<7 days after first blood culture)

Sponsors & Collaborators

• Hasselt University: lead
• Jessa Hospital: collaborator
• University of Zagreb: collaborator
• Molzym: collaborator
• AIT Austrian Institute of Technology GmbH: collaborator
• BEE Robotics: collaborator
• University of Warwick: collaborator
• Claude Bernard University: collaborator
• Axo Science: collaborator

Study Sites (1)

Jessa Hospital

Hasselt, Limburg, 3500, Belgium

Location

Related Publications (22)

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  PMID: 26903338 BACKGROUND

• Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, Angus DC, Rubenfeld GD, Singer M; Sepsis Definitions Task Force. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):775-87. doi: 10.1001/jama.2016.0289.

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• Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci. 2013 Jan-Feb;50(1):23-36. doi: 10.3109/10408363.2013.764490.

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  PMID: 22220196 BACKGROUND

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  PMID: 21398306 BACKGROUND

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  PMID: 19050640 BACKGROUND

• Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis. 2000 Jan;181(1):176-80. doi: 10.1086/315214.

  PMID: 10608764 BACKGROUND

• Rosario C, Zandman-Goddard G, Meyron-Holtz EG, D'Cruz DP, Shoenfeld Y. The hyperferritinemic syndrome: macrophage activation syndrome, Still's disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med. 2013 Aug 22;11:185. doi: 10.1186/1741-7015-11-185.

  PMID: 23968282 BACKGROUND

• Schulert GS, Grom AA. Pathogenesis of macrophage activation syndrome and potential for cytokine- directed therapies. Annu Rev Med. 2015;66:145-59. doi: 10.1146/annurev-med-061813-012806. Epub 2014 Nov 5.

  PMID: 25386930 BACKGROUND

• Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 2014 Apr;6(4):748-73. doi: 10.1039/c3mt00347g.

  PMID: 24549403 BACKGROUND

• Carcillo JA, Simon DW, Podd BS. How We Manage Hyperferritinemic Sepsis-Related Multiple Organ Dysfunction Syndrome/Macrophage Activation Syndrome/Secondary Hemophagocytic Lymphohistiocytosis Histiocytosis. Pediatr Crit Care Med. 2015 Jul;16(6):598-600. doi: 10.1097/PCC.0000000000000460. No abstract available.

  PMID: 26154908 BACKGROUND

• Bennett TD, Hayward KN, Farris RW, Ringold S, Wallace CA, Brogan TV. Very high serum ferritin levels are associated with increased mortality and critical care in pediatric patients. Pediatr Crit Care Med. 2011 Nov;12(6):e233-6. doi: 10.1097/PCC.0b013e31820abca8.

  PMID: 21263363 BACKGROUND

• Kyriazopoulou E, Leventogiannis K, Norrby-Teglund A, Dimopoulos G, Pantazi A, Orfanos SE, Rovina N, Tsangaris I, Gkavogianni T, Botsa E, Chassiou E, Kotanidou A, Kontouli C, Chaloulis P, Velissaris D, Savva A, Cullberg JS, Akinosoglou K, Gogos C, Armaganidis A, Giamarellos-Bourboulis EJ; Hellenic Sepsis Study Group. Macrophage activation-like syndrome: an immunological entity associated with rapid progression to death in sepsis. BMC Med. 2017 Sep 18;15(1):172. doi: 10.1186/s12916-017-0930-5.

  PMID: 28918754 BACKGROUND

• Shakoory B, Carcillo JA, Chatham WW, Amdur RL, Zhao H, Dinarello CA, Cron RQ, Opal SM. Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial. Crit Care Med. 2016 Feb;44(2):275-81. doi: 10.1097/CCM.0000000000001402.

  PMID: 26584195 BACKGROUND

• Antonakos N, Tsaganos T, Oberle V, Tsangaris I, Lada M, Pistiki A, Machairas N, Souli M, Bauer M, Giamarellos-Bourboulis EJ. Decreased cytokine production by mononuclear cells after severe gram-negative infections: early clinical signs and association with final outcome. Crit Care. 2017 Mar 9;21(1):48. doi: 10.1186/s13054-017-1625-1.

  PMID: 28274246 BACKGROUND

• Gainaru G, Papadopoulos A, Tsangaris I, Lada M, Giamarellos-Bourboulis EJ, Pistiki A. Increases in inflammatory and CD14dim/CD16pos/CD45pos patrolling monocytes in sepsis: correlation with final outcome. Crit Care. 2018 Mar 3;22(1):56. doi: 10.1186/s13054-018-1977-1.

  PMID: 29499723 BACKGROUND

• Drewry AM, Ablordeppey EA, Murray ET, Beiter ER, Walton AH, Hall MW, Hotchkiss RS. Comparison of monocyte human leukocyte antigen-DR expression and stimulated tumor necrosis factor alpha production as outcome predictors in severe sepsis: a prospective observational study. Crit Care. 2016 Oct 20;20(1):334. doi: 10.1186/s13054-016-1505-0.

  PMID: 27760554 BACKGROUND

• Cazalis MA, Friggeri A, Cave L, Demaret J, Barbalat V, Cerrato E, Lepape A, Pachot A, Monneret G, Venet F. Decreased HLA-DR antigen-associated invariant chain (CD74) mRNA expression predicts mortality after septic shock. Crit Care. 2013 Dec 10;17(6):R287. doi: 10.1186/cc13150.

  PMID: 24321376 BACKGROUND

• Wang AY, Ma HP, Kao WF, Tsai SH, Chang CK. Red blood cell distribution width is associated with mortality in elderly patients with sepsis. Am J Emerg Med. 2018 Jun;36(6):949-953. doi: 10.1016/j.ajem.2017.10.056. Epub 2017 Nov 10.

  PMID: 29133071 BACKGROUND

• Kim CH, Park JT, Kim EJ, Han JH, Han JS, Choi JY, Han SH, Yoo TH, Kim YS, Kang SW, Oh HJ. An increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock. Crit Care. 2013 Dec 9;17(6):R282. doi: 10.1186/cc13145.

  PMID: 24321201 BACKGROUND

• D'Onofrio V, Heylen D, Pusparum M, Grondman I, Vanwalleghem J, Meersman A, Cartuyvels R, Messiaen P, Joosten LAB, Netea MG, Valkenborg D, Ertaylan G, Gyssens IC. A prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis. J Intensive Care. 2022 Mar 9;10(1):13. doi: 10.1186/s40560-022-00602-x.

  PMID: 35264246 DERIVED

• D'Onofrio V, Van Steenkiste E, Meersman A, Waumans L, Cartuyvels R, Van Halem K, Messiaen P, Gyssens IC. Differentiating influenza from COVID-19 in patients presenting with suspected sepsis. Eur J Clin Microbiol Infect Dis. 2021 May;40(5):987-995. doi: 10.1007/s10096-020-04109-x. Epub 2020 Dec 3.

  PMID: 33274416 DERIVED

Related Links

• FAPIC project website

Biospecimen

Retention: SAMPLES WITH DNA

1 EDTA bood sample per blood culture set (2 per patient). 5mL of samples is used for validation of DNA-based diagnostics developed within the FAPIC-project. 4mL of samples is used for HLA-DR typing using flow cytometry. Left-overs are stored as plasma for future research.

MeSH Terms

Conditions

Bacteremia; Sepsis; Shock, Septic

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Inge C Gyssens, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 15, 2019
• Study Start: February 12, 2019
• Primary Completion: April 17, 2020
• Study Completion: April 17, 2020
• Last Updated: April 29, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)