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

Study Overview
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Brief Summary
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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: What is the optimal cut-off for presepsin to predict the composite endpoint all-cause mortality and MACCE? 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?

Detailed Description
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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.

Official Title
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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

Conditions
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Non Cardiac Surgery

Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Enrollment in MET-REPAIR (NCT03016936) Signed written informed consent No exclusion criteria I

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| All-cause mortality | Number of patients that die of any cause | 30 days | 
| Non-fatal cardiac arrest | Number of patients with non-fatal cardiac arrest | 30 days | 
| Myocardial infarction | Number of patients with myocardial infarction | 30 days | 
| 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 | 
| Stroke | Number of patients with stroke | 30 days | 
| Cardiovascular mortality | Number of patients that die of a cardiovascular cause | 30 days | 
| In-hospital cardiovascular mortality | Number of patients that die in hospital of a cardiovascular cause | 30 days | 
| Complications ≥ 3 in Clavien Dindo Classification | Number of patients with ≥ 3 complications in Clavien Dindo Classification | within 30 days after surgery | 
| Length of Hospital stay | Number of days participants stayed in hospital | within 30 days after surgery | 
| Length of ICU stay | Number of days participants stayed in ICU | within 30 days after surgery | 
| Myocardial injury after non-cardiac surgery (MINS) | Number of Patients with MINS | within 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Presepsin, sCD14-ST, biomarker, perioperative risk