Effect of perioperative levosimendan administration on postoperative N-terminal pro-B-type natriuretic peptide concentration in patients with increased cardiovascular risk factors undergoing non-cardiac surgery: protocol for the double-blind, randomised, placebo-controlled IMPROVE trial

• Published in: BMJ open Vol. 12; no. 1; p. e058216
• Main Authors: Reiterer, Christian, Kabon, Barbara, Taschner, Alexander, Adamowitsch, Nikolas, Graf, Alexandra, Fraunschiel, Melanie, Horvath, Katharina, Kuhrn, Melanie, Clement, Theresa, Treskatsch, Sascha, Berger, Christian, Fleischmann, Edith
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 21.01.2022; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Protocol
• Subjects: Abdomen; Abdominal surgery; adult anaesthesia; Anaesthesia; Biomarkers; Cardiovascular disease; Cardiovascular Diseases - prevention & control; clinical trials; Coronary vessels; Double-blind studies; Edema; Heart attacks; Heart Disease Risk Factors; Heart failure; Humans; Hypotheses; Ischemia; Medical imaging; Mortality; Natriuretic Peptide, Brain; Patients; Peptide Fragments; Peptides; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Simendan; Transient ischemic attack; adult anaesthesia; heart failure; clinical trials
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2021-058216

IntroductionElevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) after non-cardiac surgery is a strong predictor for cardiovascular complications and reflects increased myocardial strain. NT-pro-BNP concentrations significantly rise after non-cardiac surgery within the first 3 days. Levosimendan is a potent inotropic drug that increases calcium sensitivity to cardiac myocytes, which results in improved cardiac contractility that last for approximately 7 days. Thus, we will test the effect of a pre-emptive perioperative administration of levosimendan on postoperative NT-pro-BNP concentration as compared with the administration of a placebo in patients undergoing moderate-risk to high-risk major abdominal surgery.Methods and analysisWe will conduct a double-blinded prospective randomised trial at the Medical University of Vienna, Vienna, Austria (and potentially a second centre in Germany), including 230 patients at-risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery. Patients will be randomly assigned to receive a single dose of 12.5 mg levosimendan versus placebo after induction of anaesthesia. The primary outcome will be the postoperative maximum NT-pro-BNP concentration between both group within the first three postoperative days. Our secondary outcomes will be the incidence of myocardial ischaemia, myocardial injury after non-cardiac surgery and a composite of myocardial infarction and death within 30 days and 1 year after surgery between both groups. Our further secondary outcome will be stratification of NT-pro-BNP values according to previously thresholds to predict mortality of myocardial infarction after surgery.Ethics and disseminationThe study was approved by the Ethics Committee of the Medical University of Vienna on 14 July 2020 (EK 2187/2019). Written informed consent will be obtained from all patients a day before surgery. Results of this study will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT04329624.