Effect Levosimendan Administration on Postoperative NT-proBNP in Cardiac Risk Patients (IMPROVE)

Medical University of Vienna

Status and phase

Completed

Phase 3

Conditions

Cardiovascular Risk Factor

Treatments

Drug: Levosimendan

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT04329624

IMPROVE_2.2

Details and patient eligibility

About

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

Full 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.

Enrollment

230 patients

Sex

All

Ages

65 to 85 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

230 participants in 2 patient groups, including a placebo group

Levosimendan

Active Comparator group

Description:

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.

Treatment:

Drug: Levosimendan

Placebo

Placebo Comparator group

Description:

Patients receive a continuous infusion containing a placebo solved in 50mL for up to 24 hours. Infusion will be started with surgical skin incision.

Treatment:

Drug: Placebo