Molecular Diagnosis and Risk Stratification of Sepsis (MARS)

Study Description

Go to 

Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

Background: Sepsis is a major cause of in-hospital morbidity and mortality. Current tools available to the clinician to initiate therapy of patients with sepsis mainly comprise of symptom classification systems and culture techniques, which provide aspecific and slow information.

Objective: The ultimate goal of this program is to assist the physician at the bedside in tailoring the treatment of an individual patient suffering from sepsis by generating rapid molecular information about the causative pathogen and the host response.

Deliverables: Rapid tests ("sample-in-result-out") that can be used by health care personnel at or close to the bedside and that provide rapid information (within two hours) about the presence or absence of sepsis, the causative pathogen and the risk of the individual patient for sepsis complications and death.

Design: The program is organized into four Work Packages (WPs) along a clinical, discovery and technology platform. In WP1 two university hospitals will enroll 7500 patients admitted to the Intensive Care Unit during the first 3 years of the project; 25% - 40% of these patients will have or will develop sepsis. In WP2 (Pathogen Detection), blood obtained from these patients will be used to develop rapid, fully automated DNA-based bedside tests that identify microorganisms and also provide information about their resistance to antibiotics. In WP3 (Host Response), RNA from blood cells will be analyzed to find novel biomarkers and to develop rapid and easy to perform tests that provide information about the risk profile of the patient. In addition, plasma levels of selected protein biomarkers will be measured for comparison of their value with that of the identified leukocyte molecular signatures. WP4 is responsible for the ICT management of the project. The Clinical Platform (covered by WP1 and WP4) delivers patient data and biological samples to the discovery and technology platforms. The Discovery Platform (covered by WP2 and WP3) uses patient data and biological samples to develop tests for detection of the infectious agent causing sepsis and for stratification of patients according to their risk for sepsis complications, including death. The results generated within the discovery platform will be delivered to the technology platform. The Technology Platform (part of WP2 and WP3) has the specific aim to develop rapid assays that run on a fully automated (micro)fluidics platform that is so easy to operate that it can be used in decentralized settings such as (close to) the ICU. The developed assays will make use of the knowledge generated in the discovery platform.

Condition or disease
Sepsis

Study Design

Go to 

Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Observational [Patient Registry]
Estimated Enrollment :	7500 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Target Follow-Up Duration:	1 Year
Official Title:	Molecular Diagnosis and Risk Stratification of Sepsis
Study Start Date :	January 2011
Estimated Primary Completion Date :	June 2018
Estimated Study Completion Date :	June 2018

Groups and Cohorts

Go to 

Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Outcome Measures

Go to 

Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Molecular information about causative pathogens and the host response in patients with sepsis [ Time Frame: One year ]

Secondary Outcome Measures :

1. Stratification of septic patients by severity and type of immune response to infection [ Time Frame: Five years ]

Biospecimen Retention:   Samples With DNA

Whole blood, plasma, RNA, DNA.

Eligibility Criteria

Go to 

Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

In 3-4 years all patients> 18 years in the Intensive Care Units of the AMC Amsterdam and UMC Utrecht will be included in the study with the exemption of elective cardiac surgery patients with an uncomplicated stay.

Criteria

Inclusion Criteria:

• All patients> 18 years in the Intensive Care Units of the AMC Amsterdam and UMC Utrecht.

Exclusion Criteria:

• Elective cardiac surgery patients with an uncomplicated stay.

Contacts and Locations

Go to 

Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Tom van der Poll, Prof.	+31205665910	t.vanderpoll@amc.uva.nl

Locations

Netherlands
Academic Medical Center	Completed
Amsterdam, Noord-Holland, Netherlands, 1105 AZ
University Medical Center Utrecht	Recruiting
Utrecht, Netherlands, 3584 CX
Contact: Marc J Bonten, Prof. mbonten@umcutrecht.nl
Principal Investigator: Marc J. Bonten, Prof.

Sponsors and Collaborators

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Center for Translational Molecular Medicine

UMC Utrecht

Radboud University

Philips Healthcare

Microbiome

Immunetrics

Check-Points

Biocartis

Immunexpress

Investigators

Principal Investigator:	Tom van der Poll, Prof.	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

More Information

Go to 

Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Miller RR 3rd, Lopansri BK, Burke JP, Levy M, Opal S, Rothman RE, D'Alessio FR, Sidhaye VK, Aggarwal NR, Balk R, Greenberg JA, Yoder M, Patel G, Gilbert E, Afshar M, Parada JP, Martin GS, Esper AM, Kempker JA, Narasimhan M, Tsegaye A, Hahn S, Mayo P, van der Poll T, Schultz MJ, Scicluna BP, Klein Klouwenberg P, Rapisarda A, Seldon TA, McHugh LC, Yager TD, Cermelli S, Sampson D, Rothwell V, Newman R, Bhide S, Fox BA, Kirk JT, Navalkar K, Davis RF, Brandon RA, Brandon RB. Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU. Am J Respir Crit Care Med. 2018 Oct 1;198(7):903-913. doi: 10.1164/rccm.201712-2472OC.

Cranendonk DR, van Vught LA, Wiewel MA, Cremer OL, Horn J, Bonten MJ, Schultz MJ, van der Poll T, Wiersinga WJ. Clinical Characteristics and Outcomes of Patients With Cellulitis Requiring Intensive Care. JAMA Dermatol. 2017 Jun 1;153(6):578-582. doi: 10.1001/jamadermatol.2017.0159.

Ong DSY, Bonten MJM, Spitoni C, Verduyn Lunel FM, Frencken JF, Horn J, Schultz MJ, van der Poll T, Klein Klouwenberg PMC, Cremer OL; Molecular Diagnosis and Risk Stratification of Sepsis Consortium. Epidemiology of Multiple Herpes Viremia in Previously Immunocompetent Patients With Septic Shock. Clin Infect Dis. 2017 May 1;64(9):1204-1210. doi: 10.1093/cid/cix120.

Wiewel MA, Harmon MB, van Vught LA, Scicluna BP, Hoogendijk AJ, Horn J, Zwinderman AH, Cremer OL, Bonten MJ, Schultz MJ, van der Poll T, Juffermans NP, Wiersinga WJ. Risk factors, host response and outcome of hypothermic sepsis. Crit Care. 2016 Oct 14;20(1):328.

Klein Klouwenberg PM, Frencken JF, Kuipers S, Ong DS, Peelen LM, van Vught LA, Schultz MJ, van der Poll T, Bonten MJ, Cremer OL; MARS Consortium *. Incidence, Predictors, and Outcomes of New-Onset Atrial Fibrillation in Critically Ill Patients with Sepsis. A Cohort Study. Am J Respir Crit Care Med. 2017 Jan 15;195(2):205-211. doi: 10.1164/rccm.201603-0618OC.

McHugh L, Seldon TA, Brandon RA, Kirk JT, Rapisarda A, Sutherland AJ, Presneill JJ, Venter DJ, Lipman J, Thomas MR, Klein Klouwenberg PM, van Vught L, Scicluna B, Bonten M, Cremer OL, Schultz MJ, van der Poll T, Yager TD, Brandon RB. A Molecular Host Response Assay to Discriminate Between Sepsis and Infection-Negative Systemic Inflammation in Critically Ill Patients: Discovery and Validation in Independent Cohorts. PLoS Med. 2015 Dec 8;12(12):e1001916. doi: 10.1371/journal.pmed.1001916. eCollection 2015 Dec.

Klein Klouwenberg PM, Cremer OL, van Vught LA, Ong DS, Frencken JF, Schultz MJ, Bonten MJ, van der Poll T. Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study. Crit Care. 2015 Sep 7;19:319. doi: 10.1186/s13054-015-1035-1.

Scicluna BP, Klein Klouwenberg PM, van Vught LA, Wiewel MA, Ong DS, Zwinderman AH, Franitza M, Toliat MR, Nürnberg P, Hoogendijk AJ, Horn J, Cremer OL, Schultz MJ, Bonten MJ, van der Poll T. A molecular biomarker to diagnose community-acquired pneumonia on intensive care unit admission. Am J Respir Crit Care Med. 2015 Oct 1;192(7):826-35. doi: 10.1164/rccm.201502-0355OC.

Klein Klouwenberg PM, Zaal IJ, Spitoni C, Ong DS, van der Kooi AW, Bonten MJ, Slooter AJ, Cremer OL. The attributable mortality of delirium in critically ill patients: prospective cohort study. BMJ. 2014 Nov 24;349:g6652. doi: 10.1136/bmj.g6652.

Responsible Party:	T. van der Poll, Prof. dr. T. van der Poll, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:	NCT01905033 History of Changes
Other Study ID Numbers:	10-056
First Posted:	July 23, 2013
Last Update Posted:	April 29, 2016
Last Verified:	April 2016

Keywords provided by T. van der Poll, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Sepsis; Pneumonia; Peritonitis	Biomarkers; Transcriptomics; Pathogen detection

Additional relevant MeSH terms:

Sepsis; Toxemia; Infection	Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes