Introduction of a Prognostic Biomarker to Strengthen Risk Stratification of Acutely Admitted Patients: Rationale and Design of the TRIAGE III Cluster Randomized Interventional Trial

Overview

Journal Scand J Trauma Resusc Emerg Med

Publisher Biomed Central

Specialty Emergency Medicine

Date 2016 Aug 6

PMID 27491822

Citations 5

Authors

Andreas Sando

Martin Schultz

Jesper Eugen-Olsen

Lars Simon Rasmussen

Lars Kober

Erik Kjoller

Birgitte Nybo Jensen

Lisbet Ravn

Theis Lange

Kasper Iversen

Affiliations

Soon will be listed here.

Abstract

Background: Several biomarkers have shown to carry prognostic value beyond current triage algorithms and may aid in initial risk stratification of patients in the emergency department (ED). It has yet to be established if information provided by biomarkers can be used to prevent serious complications or deaths. Our aim is to determine whether measurement of the blood level of the biomarker soluble urokinase plasminogen activator receptor (suPAR) can enhance early risk stratification leading to reduced mortality, lower rate of complications, and improved patient flow in acutely admitted adult patients at the ED. The main hypothesis is that the availability of suPAR can reduce all-cause mortality, assessed at least 10 months after admission, by drawing attention towards patients with an unrecognized high risk, leading to improved diagnostics and treatment.

Methods: The study is designed as a cross-over cluster randomized interventional trial. SuPAR is measured within 2 h after admission and immediately reported to the treating physicians in the ED. All ED physicians are educated in the prognostic capabilities of suPAR prior to the inclusion period. The inclusion period began January 11(th) 2016 and ends June 6(th) 2016. The study aims to include 10.000 patients in both the interventional and control arm. The results will be presented in 2017.

Discussion: The present article aims to describe the design and rationale of the TRIAGE III study that will investigate whether the availability of prognostic information can improve outcome in acutely admitted patients. This might have an impact on health care organization and decision-making.

Trial Registration: The trial is registered at clinicaltrials.gov (ID NCT02643459 , November 13, 2015) and at the Danish Data Protection agency (ID HGH-2015-042 I-Suite no. 04087).

Citing Articles

Utilization of Prognostic Biomarker Soluble Urokinase Plasminogen Activator Receptor in the Emergency Department: A Tool for Safe and More Efficient Decision-making.

Holstein R, Makinen M, Castren M, Kaartinen J Biomark Insights. 2022; 17:11772719221081789.

PMID: 35295966 PMC: 8918965. DOI: 10.1177/11772719221081789.

Early Discharge from the Emergency Department Based on Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels: A TRIAGE III Substudy.

Schultz M, Rasmussen L, Hoi-Hansen T, Kjoller E, Jensen B, Lind M Dis Markers. 2019; 2019:3403549.

PMID: 31236143 PMC: 6545801. DOI: 10.1155/2019/3403549.

Risk assessment models for potential use in the emergency department have lower predictive ability in older patients compared to the middle-aged for short-term mortality - a retrospective cohort study.

Schultz M, Hartmann Rasmussen L, Carlson N, Hasselbalch R, Jensen B, Usinger L BMC Geriatr. 2019; 19(1):134.

PMID: 31096925 PMC: 6521424. DOI: 10.1186/s12877-019-1154-7.

Availability of suPAR in emergency departments may improve risk stratification: a secondary analysis of the TRIAGE III trial.

Schultz M, Rasmussen L, Kallemose T, Kjoller E, Lind M, Ravn L Scand J Trauma Resusc Emerg Med. 2019; 27(1):43.

PMID: 30975178 PMC: 6458624. DOI: 10.1186/s13049-019-0621-7.

Use of the prognostic biomarker suPAR in the emergency department improves risk stratification but has no effect on mortality: a cluster-randomized clinical trial (TRIAGE III).

Schultz M, Hartmann Rasmussen L, Andersen M, Stefansson J, Falkentoft A, Alstrup M Scand J Trauma Resusc Emerg Med. 2018; 26(1):69.

PMID: 30153859 PMC: 6114851. DOI: 10.1186/s13049-018-0539-5.

References

Iversen K, Gotze J, Dalsgaard M, Nielsen H, Boesgaard S, Bay M . Risk stratification in emergency patients by copeptin. BMC Med. 2014; 12:80. PMC: 4053286. DOI: 10.1186/1741-7015-12-80. View

Trentino K, Swain S, Burrows S, Sprivulis P, Daly F . Measuring the incidence of hospital-acquired complications and their effect on length of stay using CHADx. Med J Aust. 2013; 199(8):543-7. DOI: 10.5694/mja12.11640. View

Gumus A, Altintas N, Cinarka H, Kirbas A, Haziroglu M, Karatas M . Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD. Int J Chron Obstruct Pulmon Dis. 2015; 10:357-65. PMC: 4334296. DOI: 10.2147/COPD.S77654. View

OCathain A, Knowles E, Turner J, Hirst E, Goodacre S, Nicholl J . Variation in avoidable emergency admissions: multiple case studies of emergency and urgent care systems. J Health Serv Res Policy. 2015; 21(1):5-14. DOI: 10.1177/1355819615596543. View

Shewale J, Correa A, Baker C, Villafane-Ferriol N, Hofstetter W, Jordan V . Impact of a Fast-track Esophagectomy Protocol on Esophageal Cancer Patient Outcomes and Hospital Charges. Ann Surg. 2014; 261(6):1114-23. PMC: 4838458. DOI: 10.1097/SLA.0000000000000971. View

Fuhrman B . The urokinase system in the pathogenesis of atherosclerosis. Atherosclerosis. 2011; 222(1):8-14. DOI: 10.1016/j.atherosclerosis.2011.10.044. View

Fromm R, Meyer D, Zimmerman J, Boudreaux A, Wun C, Smalling R . A double-blind, multicentered study comparing the accuracy of diagnostic markers to predict short- and long-term clinical events and their utility in patients presenting with chest pain. Clin Cardiol. 2001; 24(7):516-20. PMC: 6654932. DOI: 10.1002/clc.4960240708. View

Lyngbaek S, Sehestedt T, Marott J, Hansen T, Olsen M, Andersen O . CRP and suPAR are differently related to anthropometry and subclinical organ damage. Int J Cardiol. 2012; 167(3):781-5. DOI: 10.1016/j.ijcard.2012.03.040. View

Botha S, Fourie C, Schutte R, Eugen-Olsen J, Pretorius R, Schutte A . Soluble urokinase plasminogen activator receptor as a prognostic marker of all-cause and cardiovascular mortality in a black population. Int J Cardiol. 2015; 184:631-636. DOI: 10.1016/j.ijcard.2015.03.041. View

10.

Reichsoellner M, Raggam R, Wagner J, Krause R, Hoenigl M . Clinical evaluation of multiple inflammation biomarkers for diagnosis and prognosis for patients with systemic inflammatory response syndrome. J Clin Microbiol. 2014; 52(11):4063-6. PMC: 4313254. DOI: 10.1128/JCM.01954-14. View

11.

Basse L, Thorbol J, Lossl K, Kehlet H . Colonic surgery with accelerated rehabilitation or conventional care. Dis Colon Rectum. 2004; 47(3):271-7. DOI: 10.1007/s10350-003-0055-0. View

12.

Zimmermann H, Koch A, Seidler S, Trautwein C, Tacke F . Circulating soluble urokinase plasminogen activator is elevated in patients with chronic liver disease, discriminates stage and aetiology of cirrhosis and predicts prognosis. Liver Int. 2011; 32(3):500-9. DOI: 10.1111/j.1478-3231.2011.02665.x. View

13.

Hillis G, Zhao N, Taggart P, Dalsey W, Mangione A . Utility of cardiac troponin I, creatine kinase-MB(mass), myosin light chain 1, and myoglobin in the early in-hospital triage of "high risk" patients with chest pain. Heart. 1999; 82(5):614-20. PMC: 1760765. DOI: 10.1136/hrt.82.5.614. View

14.

Madsen F, Ladelund S, Linneberg A . High levels of bed occupancy associated with increased inpatient and thirty-day hospital mortality in Denmark. Health Aff (Millwood). 2014; 33(7):1236-44. DOI: 10.1377/hlthaff.2013.1303. View

15.

Raggam R, Wagner J, Pruller F, Grisold A, Leitner E, Zollner-Schwetz I . Soluble urokinase plasminogen activator receptor predicts mortality in patients with systemic inflammatory response syndrome. J Intern Med. 2014; 276(6):651-8. DOI: 10.1111/joim.12238. View

16.

Schuetz P, Hausfater P, Amin D, Amin A, Haubitz S, Faessler L . Biomarkers from distinct biological pathways improve early risk stratification in medical emergency patients: the multinational, prospective, observational TRIAGE study. Crit Care. 2015; 19:377. PMC: 4625457. DOI: 10.1186/s13054-015-1098-z. View

17.

Lyngbaek S, Marott J, Sehestedt T, Hansen T, Olsen M, Andersen O . Cardiovascular risk prediction in the general population with use of suPAR, CRP, and Framingham Risk Score. Int J Cardiol. 2012; 167(6):2904-11. DOI: 10.1016/j.ijcard.2012.07.018. View

18.

Blasi F, Sidenius N . The urokinase receptor: focused cell surface proteolysis, cell adhesion and signaling. FEBS Lett. 2009; 584(9):1923-30. DOI: 10.1016/j.febslet.2009.12.039. View

19.

Thuno M, Macho B, Eugen-Olsen J . suPAR: the molecular crystal ball. Dis Markers. 2009; 27(3):157-72. PMC: 3835059. DOI: 10.3233/DMA-2009-0657. View

20.

Haupt T, Petersen J, Ellekilde G, Klausen H, Thorball C, Eugen-Olsen J . Plasma suPAR levels are associated with mortality, admission time, and Charlson Comorbidity Index in the acutely admitted medical patient: a prospective observational study. Crit Care. 2012; 16(4):R130. PMC: 3580714. DOI: 10.1186/cc11434. View