Biomarkers, Blood Pressure, BIS: Risk Stratification/Management of Patients at Cardiac Risk in Major Noncardiac Surgery

NCT02533128 | Completed DMC

• 1 other identifier: EKSG 15/003
• Study Type: interventional
• Target: 458
• Locations: 1 country
• Sites: 1

Brief Summary

Major adverse cardiovascular events (MACE) are a leading cause of serious complications and death following major noncardiac surgery. The heart biomarkers brain-type natriuretic peptide (BNP) and high-sensitivity troponin I/T (hs-TnI/T), may aid in estimating the risk of surgery - low values may permit identifying patients at a very low risk of postoperative complications, potentially helping to avoid unnecessary tests and delays prior to surgery. Recent studies suggest that the manner in which an anesthetic is conducted may have an important impact on postoperative outcomes. The combination of low blood pressure (BP) and a deep level of anesthesia despite a low dose of anesthetic - also known as a "triple low" - has been linked to increased complications and death following surgery. However, it is unclear whether triple lows actually cause postoperative complications or whether they are merely an indicator of a sick patient, who is in general more likely to suffer from cardiovascular events in the near future. To answer this question, in this study patients will be randomly assigned to groups with lower and higher blood pressures, and the postoperative rates of major adverse cardiovascular events and of relevant increases in hs-TnI (a marker of cardiac injury) compared. Another important question is that of the optimal blood pressure target during surgery. Currently there are no established methods of tailoring blood pressure management to the individual patient. In the study the investigators will perform ambulatory 24h BP measurements prior to surgery to measure the patients' average BP during sleep. In the analysis of the study data, the investigators will try to determine the relationship of preoperative biomarker levels, intraoperative BP (both in relation to fixed targets and to the patient's own night-time BP) and of anesthetic depth with the occurrence of major adverse cardiovascular events after surgery.

Conditions

Hypotension; Postoperative Complications; Acute Coronary Syndrome; Heart Failure; Coronary Occlusion; Stroke; Acute Kidney Injury; Renal Insufficiency, Chronic; Death

Keywords

Intraoperative blood pressure; Triple low; Anesthetic overdose; Major adverse cardiac events (MACE); Myocardial injury after noncardiac surgery (MINS); Perioperative risk stratification; Brain-type natriuretic peptide (BNP); High-sensitivity cardiac Troponin I (hs-cTnI)

Outcome Measures

Primary Outcomes (2)

• High-sensitivity cardiac Troponin I (hs-cTnI) > 0.04ng/ml and >= 35% relative increase compared to preoperative value

  Postoperative days 0-3

• Major adverse cardiovascular events

  Acute coronary syndrome, new or worsening congestive heart failure, coronary revascularization, stroke, acute kidney injury, all-cause mortality

  30 days postoperatively

Secondary Outcomes (1)

• Major adverse cardiovascular events

  1 year postoperatively

Study Arms (2)

Liberal blood pressure management

PLACEBO COMPARATOR

Drug: Liberal blood pressure management

Tight blood pressure management

ACTIVE COMPARATOR

Drug: Tight blood pressure management

Interventions

Liberal blood pressure management DRUG

Protocolized hemodynamic management to maintain mean arterial pressure (MAP) \> 60 mmHg

Liberal blood pressure management

Tight blood pressure management DRUG

Protocolized hemodynamic management to maintain mean arterial pressure (MAP) \> 75 mmHg

Tight blood pressure management

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A) undergoing major noncardiac surgery, defined as:
• vascular surgery (with the exception of arteriovenous shunt, vein stripping procedures and carotid endarterectomies)
• intraperitoneal surgery
• intrathoracic surgery
• major orthopedic surgery
• B) at cardiovascular risk, defined as meeting at least 1 of the following 6 criteria:
• history of coronary artery disease
• history of peripheral vascular disease
• history of stroke
• hospitalization for congestive heart failure
• undergoing major vascular surgery, with the exception of arteriovenous shunt, vein stripping procedures and carotid endarterectomies
• fulfillment of any 3 of the 7 Lee criteria, defined as:
• undergoing intrathoracic or intraperitoneal surgery
• anamnestic transient ischemic attack (TIA)
• any history of CHF or history of pulmonary edema

You may not qualify if:

• General
• pregnancy
• previously enrolled in BBB Study
• RCT
• emergent surgery
• presence of any active cardiac conditions:
• unstable coronary syndromes: unstable or severe (CCS III or IV) angina
• decompensated heart failure: NYHA IV, worsening or new-onset
• significant arrhythmias: high-grade AV-block (Mobitz II and third-degree), symptomatic bradycardia, symptomatic ventricular arrhythmias, supraventricular arrhythmias with uncontrolled ventricular rate (\>100bpm at rest), newly recognized ventricular tachycardia
• severe valvular disease: severe aortic stenosis (mean pressure gradient \> 40 mmHg, aortic valve area \< 1.0 cm2, symptomatic), symptomatic mitral stenosis (progressive dyspnea on exertion, externional presyncope, heart failure)
• any transplantation

Sponsors & Collaborators

• Miodrag Filipovic, Prof. Dr. med.: lead

Study Sites (1)

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Publications (5)

• Sessler DI, Sigl JC, Kelley SD, Chamoun NG, Manberg PJ, Saager L, Kurz A, Greenwald S. Hospital stay and mortality are increased in patients having a "triple low" of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia. Anesthesiology. 2012 Jun;116(6):1195-203. doi: 10.1097/ALN.0b013e31825683dc.

  PMID: 22546967 BACKGROUND

• Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Buller CE, Creager MA, Ettinger SM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Ornato JP, Page RL, Tarkington LG, Yancy CW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery); American Society of Echocardiography; American Society of Nuclear Cardiology; Heart Rhythm Society; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society for Vascular Surgery. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation. 2007 Oct 23;116(17):e418-99. doi: 10.1161/CIRCULATIONAHA.107.185699. Epub 2007 Sep 27. No abstract available.

  PMID: 17901357 BACKGROUND

• 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. 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. Circulation. 2014 Dec 9;130(24):e278-333. doi: 10.1161/CIR.0000000000000106. Epub 2014 Aug 1. No abstract available.

  PMID: 25085961 BACKGROUND

• Kristensen SD, Knuuti J, Saraste A, Anker S, Botker HE, Hert SD, Ford I, Gonzalez-Juanatey JR, Gorenek B, Heyndrickx GR, Hoeft A, Huber K, Iung B, Kjeldsen KP, Longrois D, Luscher TF, Pierard L, Pocock S, Price S, Roffi M, Sirnes PA, Sousa-Uva M, 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 Heart J. 2014 Sep 14;35(35):2383-431. doi: 10.1093/eurheartj/ehu282. Epub 2014 Aug 1. No abstract available.

  PMID: 25086026 BACKGROUND

• Wanner PM, Wulff DU, Djurdjevic M, Korte W, Schnider TW, Filipovic M. Targeting Higher Intraoperative Blood Pressures Does Not Reduce Adverse Cardiovascular Events Following Noncardiac Surgery. J Am Coll Cardiol. 2021 Nov 2;78(18):1753-1764. doi: 10.1016/j.jacc.2021.08.048.

  PMID: 34711333 DERIVED

MeSH Terms

Conditions

Hypotension; Postoperative Complications; Acute Coronary Syndrome; Heart Failure; Coronary Occlusion; Stroke; Acute Kidney Injury; Renal Insufficiency, Chronic; Death; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myocardial Ischemia; Heart Diseases; Coronary Disease; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes

Study Officials

• Miodrag Filipovic, Prof. Dr.

  Cantonal Hospital of St. Gallen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice-Chairman, Clinic for Anesthesiology, Intensive Care, Prehospital and Pain Medicine

Study Record Dates

• First Submitted: August 24, 2015
• First Posted: August 26, 2015
• Study Start: October 14, 2015
• Primary Completion: May 17, 2019
• Study Completion: April 17, 2020
• Last Updated: July 15, 2020

Record last verified: 2020-07

Locations

CH (1)