Clinical trial NCT04329624: Effect Levosimendan Administration on Postoperative NT-proBNP in Cardiac Risk Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Risk Factor
Keywords: Levosimendan
NT-proBNP
MINS
Cardiovascular Disease
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2020-04-01
Enrollment: 230
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective randomised trial investigating the effect of a preemptive administration of levosimendan on postoperative cardiac NT-proBNP concentrations.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

All patients need to meet all of the following criteria for inclusion (1-4):

1. Undergoing major surgery planned for more than 2 hours
2. ≥ 65 years of age and ≤ 85 years of age
3. Provide written informed consent AND
4. 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

Exclusion Criteria:

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

Primary outcomes:
measure: Postoperative maximum NT-proBNP concentration
timeFrame: First 5 Postoperative Days
Secondary outcomes:
measure: Postoperative maximum troponin T concentration
timeFrame: First five postoperative days
measure: Incidence of MINS (myocardial injury in non cardiac surgery)
timeFrame: First three postoperative days
measure: Myocardial Infarction
timeFrame: 30 days and 1 year after surgery
measure: Disability
timeFrame: 30 days and 1 year after surgery
measure: NT-proBNP Mortality
timeFrame: 30 days and 1 year after surgery
Other outcomes:
measure: Sub-Study I: Fluid status determination
timeFrame: within 5 days after surgery
measure: Sub-Study II: Acute Kidney Injury
timeFrame: within 5 days after surgery
measure: Sub-Study III: Inflammatory Response
timeFrame: within 5 days after surgery
measure: Sub-Study IV: Neurocognitive decline
timeFrame: within first 5 postoperative days and 1 year after surgery
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
References:
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