Presepsin (sCD14-ST) for Prediction of Perioperative Risk - MET-REPAIR Nested Cohort Study

Non Cardiac Surgery Clinical Trial

— P^3-MET-REPAIR  

Official title:

MET: REevaluation for Perioperative cArdIac Risk (MET-REPAIR): a Prospective, Multi-centre Cohort Observational Study- Presepsin (sCD14-ST) for Perioperative Risk Prediction Nested Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03489486
• Other study ID #: MET-REPAIR PRESEPSIN
• Status: Recruiting
• Start date: June 15, 2018
• Est. completion date: April 30, 2019

Study information

• Verified date: September 2018
• Source: University Hospital Heidelberg
• Contact: Jan Larmann, MD/PhD
• Phone: +49 6221 56
• Email: jan.larmann[@]med.uni-heidelberg.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Multicentre international prospective cohort study designed to evaluate whether preoperative presepsin (sCD14-ST) is associated with the composite endpoint: all-cause mortality and major adverse cardiovascular or cerebrovascular events (MACCE) after elevated risk non-cardiac surgery. If so:

1. What is the optimal cut-off for presepsin to predict the composite endpoint all-cause mortality and MACCE?

2. Does the calculated optimal cut-off improve prediction of the composite endpoint all-cause mortality and MACCE when added to clinical data and established biomarkers?

Description:

Major non-cardiac surgery is still associated with relevant cardiovascular mortality and morbidity. In Europe, in-hospital mortality exceeded 7% in patients with coronary artery disease and in those with congestive heart failure. Within 30 days of non-cardiac surgery procedures, 8% of patients will suffer a major cardiovascular event.

Immunological processes, increased recruitment and infiltration of innate and adaptive immune cells into atherosclerotic lesions, have been shown to drive perioperative atherosclerotic lesion progression and plaque destabilization and are thought to promote plaque rupture. When classical monocytes are activated to inflammatory non-classical monocytes, the membrane-bound cell surface protein CD14 is released into circulation. In plasma, soluble CD14 (sCD14) is cleaved by lysosomal proteases. The N-terminal 13kDa fragment constitutes sCD14 subtype (sCD14-ST), also called presepsin. Presepsin has been established as a marker for early identification of patients with systemic infections. Recently, presepsin has been proposed as a biomarker for preoperative risk prediction in cardiac surgery. Our preliminary results in a limited number of patients suggest that presepsin is associated with major adverse cardiovascular and cerebrovascular events after non-cardiac surgery as well with all-cause mortality. Presepsin might have a test characteristic superior to conventional risk assessment on the basis of the revised cardiac risk index (RCRI), high-sensitivity cardiac Troponin-T (hs-cTnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP).

Preoperative presepsin quantification might help to identify non-cardiac surgery patients prone to experience perioperative major adverse cardiovascular and cerebrovascular events.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1695
• Est. completion date: April 30, 2019
• Est. primary completion date: April 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

Inclusion criteria:

• Enrollment in MET-REPAIR (NCT03016936)

• Signed written informed consent

No exclusion criteria

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Related Conditions & MeSH terms

• Non Cardiac Surgery

Locations

Country	Name	City	State
Germany	Department of Anaesthesiology, University Hospital Heidelberg	Heidelberg	Baden-Württemberg

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Heidelberg	European Society of Anaesthesiology

Country where clinical trial is conducted

Germany, 

References & Publications (6)

Devereaux PJ, Mrkobrada M, Sessler DI, Leslie K, Alonso-Coello P, Kurz A, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, VanHelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Baigent C, Chow C, Pettit S, Chrolavicius S, Yusuf S; POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014 Apr 17;370(16):1494-503. doi: 10.1056/NEJMoa1401105. Epub 2014 Mar 31. — View Citation

Fleisher LA, Fleischmann KE, Auerbach AD, Barnason SA, Beckman JA, Bozkurt B, Davila-Roman VG, Gerhard-Herman MD, Holly TA, Kane GC, Marine JE, Nelson MT, Spencer CC, Thompson A, Ting HH, Uretsky BF, Wijeysundera DN; American College of Cardiology; American Heart Association. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014 Dec 9;64(22):e77-137. doi: 10.1016/j.jacc.2014.07.944. Epub 2014 Aug 1. — View Citation

Gupta PK, Gupta H, Sundaram A, Kaushik M, Fang X, Miller WJ, Esterbrooks DJ, Hunter CB, Pipinos II, Johanning JM, Lynch TG, Forse RA, Mohiuddin SM, Mooss AN. Development and validation of a risk calculator for prediction of cardiac risk after surgery. Circulation. 2011 Jul 26;124(4):381-7. doi: 10.1161/CIRCULATIONAHA.110.015701. Epub 2011 Jul 5. — View Citation

Kristensen SD, Knuuti J, Saraste A, Anker S, Bøtker HE, De Hert S, Ford I, Gonzalez Juanatey JR, Gorenek B, Heyndrickx GR, Hoeft A, Huber K, Iung B, Kjeldsen KP, Longrois D, Luescher TF, Pierard L, Pocock S, Price S, Roffi M, Sirnes PA, Uva MS, Voudris V, Funck-Brentano C; Authors/Task Force Members. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur J Anaesthesiol. 2014 Oct;31(10):517-73. doi: 10.1097/EJA.0000000000000150. Review. — View Citation

Lee TH, Marcantonio ER, Mangione CM, Thomas EJ, Polanczyk CA, Cook EF, Sugarbaker DJ, Donaldson MC, Poss R, Ho KK, Ludwig LE, Pedan A, Goldman L. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation. 1999 Sep 7;100(10):1043-9. — View Citation

Pearse RM, Moreno RP, Bauer P, Pelosi P, Metnitz P, Spies C, Vallet B, Vincent JL, Hoeft A, Rhodes A; European Surgical Outcomes Study (EuSOS) group for the Trials groups of the European Society of Intensive Care Medicine and the European Society of Anaesthesiology. Mortality after surgery in Europe: a 7 day cohort study. Lancet. 2012 Sep 22;380(9847):1059-65. doi: 10.1016/S0140-6736(12)61148-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of intra- and postoperative in hospital all-cause mortality, non-fatal cardiac arrest, acute myocardial infarction, congestive heart failure requiring transfer to a higher unit of care or prolonging stay on ICU/intermediate care =24h and stroke	Number of Patients with Composite of intra- and postoperative in hospital all-cause mortality, non-fatal cardiac arrest, acute myocardial infarction, congestive heart failure requiring transfer to a higher unit of care or prolonging stay on ICU/intermediate care =24h and stroke	at discharge or at day 30 after surgery (whatever comes first)
Secondary	Composite of intra- and postoperative in hospital all-cause mortality, non-fatal cardiac arrest, acute myocardial infarction, congestive heart failure requiring transfer to a higher unit of care or prolonging stay on ICU/intermediate care =24h and stroke	Number of Patients with composite of intra- and postoperative in hospital all-cause mortality, non-fatal cardiac arrest, acute myocardial infarction, congestive heart failure requiring transfer to a higher unit of care or prolonging stay on ICU/intermediate care =24h and stroke for patients recruited in centers conducting 30-day follow-up	30 days
Secondary	All-cause mortality	Number of patients that die of any cause	30 days
Secondary	Non-fatal cardiac arrest	Number of patients with non-fatal cardiac arrest	30 days
Secondary	Myocardial infarction	Number of patients with myocardial infarction	30 days
Secondary	Congestive heart failure requiring transfer to a higher unit of care or prolonging stay on ICU/intermediate care (=24h)	Number of patients with congestive heart failure requiring transfer to a higher unit of care or prolonging stay on ICU/intermediate care (=24h)	30 days
Secondary	Stroke	Number of patients with stroke	30 days
Secondary	Cardiovascular mortality	Number of patients that die of a cardiovascular cause	30 days
Secondary	In-hospital cardiovascular mortality	Number of patients that die in hospital of a cardiovascular cause	30 days
Secondary	Complications = 3 in Clavien Dindo Classification	Number of patients with = 3 complications in Clavien Dindo Classification	within 30 days after surgery
Secondary	Length of Hospital stay	Number of days participants stayed in hospital	within 30 days after surgery
Secondary	Length of ICU stay	Number of days participants stayed in ICU	within 30 days after surgery
Secondary	Myocardial injury after non-cardiac surgery (MINS)	Number of Patients with MINS	within 30 days after surgery