The Effect of Perioperative LevosIMendan Administration on Postoperative N-terminal pRo Brain Natriuretic Peptide Concentration in Patients With Increased cardiOVascular Risk Factors Undergoing Noncardiac surgEry - A Double-blinded Randomized Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 230
- 试验地点
- 1
- 主要终点
- Postoperative maximum NT-proBNP concentration
研究概览
简要总结
This is a prospective randomised trial investigating the effect of a preemptive administration of levosimendan on postoperative cardiac NT-proBNP concentrations.
详细描述
Major cardiovascular complications occur in about 3 % of all patients undergoing noncardiac surgery and are even higher in patients with increased preoperative risk factors. N-terminal pro brain natriuretic peptide (NT-proBNP) increases in over two third of patients undergoing surgery and is a strong predictor for perioperative myocardial complications. Levosimendan is a positive inotropic Ca2+ sensitizer and significantly reduces postoperative BNP concentration in cardiac surgery. The evidence in the non-cardiac surgery setting, however, is weak. Therefore, we will test our primary hypothesis that the perioperative administration of levosimendan significantly will reduce postoperative NT-proBNP concentrations in patients undergoing moderate- to high-risk non-cardiac surgery. We will also test the secondary hypotheses that levosimendan will reduce postoperative maximum troponin T (maxTnT) concentration, the incidence of myocardial injury after noncardiac surgery (MINS), myocardial infarction and death within 30 days and one year after surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 85 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients need to meet all of the following criteria for inclusion (1-4):
- •Undergoing major surgery planned for more than 2 hours
- •≥ 65 years of age and ≤ 85 years of age
- •Provide written informed consent AND
- •Fulfill ≥ 2 of the following criteria (A-E)
- •A) NT-proBNP ≥ 200 ng/L
- •B) History of coronary artery disease defined as 1 of the following 7 criteria (I to VII):
- •I) History of angina
- •II) History of myocardial infarction or acute coronary syndrome
- •III) History of a segmental cardiac wall motion abnormality on echocardiography/radionuclide imaging
- •IV) History of positive myocardial stress test (echocardiographic or radionuclide)
- •V) History of a coronary artery stenosis > 50%
- •VI) ECG with pathological Q waves in any two contiguous leads
- •VII) History of previous artery revascularizations
- •C) History of permanent/paroxysmal atrial fibrillation diagnosed by physician/specialist
- •D) History of peripheral arterial disease as defined by a physician/specialist diagnosis of a current, or prior history of any 1 of the following 5criteria (I-V)
- •I) Intermittent claudication
- •II) Stenosis ≥ 70 % detected by angiography or doppler
- •III) Stenosis ≤ 70% detected by angiography or doppler AND requiring medical treatment e.g. ASA or other platelet inhibitor
- •IV) History of stroke or TIA - diagnosed by physician or CT/MRI
- •V) Diagnosed cerebral arteriovascular disease (cAVK) diagnosed by a physician/specialist
- •E) Any 3 of 10 of the following risk criteria (i - x).
- •i. History of congestive heart failure defined as a physician diagnosis of a current or prior episode of congestive heart failure OR prior radiographic evidence of vascular redistribution, interstitial pulmonary edema, or frank alveolar pulmonary edema;
- •ii. History of a transient ischemic attack;
- •iii. Diabetes and currently taking an oral hypoglycemic agent or insulin;
- •iv. History of hypertension;
- •v. Hyperlipidemia and currently taking a lipid lowering agent;
- •vi. Documented chronic kidney disease diagnosed by physician/specialist and creatinine clearance > 30 ml/min
- •vii. History of smoking within 2 years of surgery
- •viii. Diastolic dysfunction (≥ grade 1) documented by echocardiography
- •ix. Age ≥ 70 years
- •x. Preoperative Troponin T (5th generation) ≥ 25ng/dL
排除标准
- •A) Previous adverse response and/or allergy to levosimendan B) ICU Patients undergoing surgery C) Preoperative Sepsis/SIRS needing ICU treatment D) Preoperative hemodynamically instable patients, who requirevasopressor or inotropic support E) Renal or liver transplantation F) History of severe heart failure (e.g. LVEF < 30%) G) Patients undergoing surgery for pheochromocytoma H) Liver cirrhosis I) Pulmonary hypertension (mPAP > 25 mmHg) J) Severe Renal Failure defines as creatinine clearance ≤ 30ml/min
研究组 & 干预措施
Levosimendan
Patients receive a continuous infusion of 12.5mg solved in 50mL Levosimendan for up to 24 hours. Infusion will be started with surgical skin incision.
干预措施: Levosimendan (Drug)
Placebo
Patients receive a continuous infusion containing a placebo solved in 50mL for up to 24 hours. Infusion will be started with surgical skin incision.
干预措施: Placebo (Drug)
结局指标
主要结局
Postoperative maximum NT-proBNP concentration
时间窗: First 5 Postoperative Days
The administration of levosimendan improves LVEF and myocardial oxygen perfusion, which will be reflected in a decrease of postoperative NT-proBNP concentration.Since NT-proBNP is a strong predictor for postoperative cardiovascular complications in patients undergoing noncardiac surgery, we want to test the efficiency of levosimendan to decrease postoperative maxNT-proBNP concentrations in patients with increased cardiac risk factors undergoing moderate- to high-risk noncardiac surgery.
次要结局
- Postoperative maximum troponin T concentration(First five postoperative days)
- Incidence of MINS (myocardial injury in non cardiac surgery)(First three postoperative days)
- Myocardial Infarction(30 days and 1 year after surgery)
- NT-proBNP Mortality(30 days and 1 year after surgery)
- Disability(30 days and 1 year after surgery)
研究者
Edith Fleischmann
Ao. Univ. Prof. Dr. Edith Fleischmann
Medical University of Vienna