AzTrials
AzTrials

Cardiovascular Risk FactorPhase 3IMPROVENCT04329624

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

A Phase 3 study testing Levosimendan in people with Cardiovascular Risk Factor, run by Medical University of Vienna at 1 site in Austria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 65 to 85 years
Conditions the study is for
Cardiovascular Risk Factor
What is being tested?
Levosimendan
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
230 participants
Where
1 siteAustria
Study dates
10 Oct 2020to 18 Dec 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 to 85 years
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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)
  • NT-proBNP ≥ 200 ng/L
Show all 32Show fewer
  • 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
  • History of permanent/paroxysmal atrial fibrillation diagnosed by physician/specialist
  • 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
  • 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

Who cannot join

  • 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 locations and contacts

1 site in 1 country.

Austria1 site

  • Medical University of Vienna

    Vienna, State of Vienna, 1100

Other trials in Austria

About this study

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

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

Read the 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.

Being tested
Levosimendan, Placebo
Keywords
Levosimendan, NT-proBNP, MINS, Cardiovascular Disease
Medical subject headings
Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LevosimendanDrug

    Levosimendan 2.5 mg/ml injection contains levosimendan 2.5 mg, povidone 10.0 mg, citric acid, anhydrous 2.0 mg and ethanol, anhydrous to 1.0 mL. Levosimendan injection is a clear, yellow to orange solution. Immediately after skin incision patients allocated to the verum group will receive a dose of 12.5 mg in 500 mL of levosimendan.

  • PlaceboDrug

    Placebo 2.5 mg/ml injection contains riboflavine sodium phosphate 0.4 mg, dehydrated alcohol 100 mg and water for injection to 1 mL.

    Immediately after skin incision patients allocated to the placebo group will receive 500 mL of 5% Glucose.

Study groups in NCT04329624
Study groupRoleWhat they receive
LevosimendanActive comparatorPatients receive a continuous infusion of 12.5mg solved in 50mL Levosimendan for up to 24 hours. Infusion will be started with surgical skin incision.
Receives: Drug: Levosimendan
PlaceboPlacebo comparatorPatients receive a continuous infusion containing a placebo solved in 50mL for up to 24 hours. Infusion will be started with surgical skin incision.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Postoperative maximum NT-proBNP concentration

    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.

    Measured: First 5 Postoperative Days

Secondary outcomes (5)

  1. Postoperative maximum troponin T concentration

    Levosimendan improves myocardial perfusion and might therefore reduce the postoperative maximum rise in TnT

    Measured: First five postoperative days

  2. Incidence of MINS (myocardial injury in non cardiac surgery)

    Levosimendan decreases the incidence of MINS during the first 3 postoperative days as compared to placebo in patients with increased cardiovascular risk factors undergoing moderateto high-risk noncardiac surgery. MINS is defined as: (i) a non-high-sensitivity troponin T >_30ng/L2 and (ii) a high-sensitivity troponin T (hsTnT) of 20 to <65 ng/L with an absolute change of at least 5 ng/L-this change threshold is independently associated with 30-day mortality [hazard ratio (HR) 4.69; 95% confidence interval (CI) 3.52-6.25]-or an hsTnT level >_65ng/ L. Furthermore, an absolute change of at least 5 ng/L is independently associated with 30-day mortality and will also be defined as MINS. TnT will be measured within 2 hours after surgery, on the first, second and third postoperative day.

    Measured: First three postoperative days

  3. Myocardial Infarction

    Levosimendan reduces the event rates of myocardial infarction and death during 30 days and 1 year after surgery as compared to placebo. Myocardial infarction is defined as a rise of TnT at least one value is above the 99th percentile URL and with at least one of the following: (i) symptoms of acute myocardial ischaemia; (ii) new ischaemic ECG changes; (iii) development of pathological Q waves; (iiii) imaging evidence of new loss of viable myocardium; (v) new regional wall motion abnormality in a pattern consistent with an ischemic ethiology; (vi) identification of a coronary thrombus by angiography including intracoronary imaging or autopsy.

    Measured: 30 days and 1 year after surgery

  4. Disability

    We evaluate the WHODAS 2.0 score before surgery on the day of consent, 30 days after surgery, and 1 year after surgery per phone call. For analyzing we use simply scoring. Each score is assigned to each of the following items - "none" (0), "mild" (1), "moderate" (2), "severe" (3), and "extreme (4).

    We will simply add up the scores from the items without recoding or collapsing of response categories, thus, there is no weighting of the individual items. As a result, the simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations.

    Measured: 30 days and 1 year after surgery

  5. NT-proBNP Mortality

    Perioperative NT-proBNP elevations are associated with postoperative mortality, cardiac mortality, mortality and nonfatal MI, and cardiac failure at both 30 days and 180 days or more after surgery.

    NT-proBNP values have been stratified to the previous published thresholds to predict mortality or MI after surgery.

    Measured: 30 days and 1 year after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2020
  2. Study start10 Oct 2020
  3. Primary completion7 Nov 2023
  4. Study completion18 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
230 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04329624
Sponsor's protocol ID
IMPROVE_2.2
Acronym
IMPROVE
Status last verified
Apr 2025
First submitted
27 Mar 2020
Last updated
8 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Rodseth RN, Biccard BM, Chu R, Lurati Buse GA, Thabane L, Bakhai A, Bolliger D, Cagini L, Cahill TJ, Cardinale D, Chong CP, Cnotliwy M, Di Somma S, Fahrner R, Lim WK, Mahla E, Le Manach Y, Manikandan R, Pyun WB, Rajagopalan S, Radovic M, Schutt RC, Sessler DI, Suttie S, Vanniyasingam T, Waliszek M, Devereaux PJ. Postoperative B-type natriuretic peptide for prediction of major cardiac events in patients undergoing noncardiac surgery: systematic review and individual patient meta-analysis. Anesthesiology. 2013 Aug;119(2):270-83. doi: 10.1097/ALN.0b013e31829083f1.

    PubMed 23528538

  • Writing Committee for the VISION Study Investigators; Devereaux PJ, Biccard BM, Sigamani A, Xavier D, Chan MTV, Srinathan SK, Walsh M, Abraham V, Pearse R, Wang CY, Sessler DI, Kurz A, Szczeklik W, Berwanger O, Villar JC, Malaga G, Garg AX, Chow CK, Ackland G, Patel A, Borges FK, Belley-Cote EP, Duceppe E, Spence J, Tandon V, Williams C, Sapsford RJ, Polanczyk CA, Tiboni M, Alonso-Coello P, Faruqui A, Heels-Ansdell D, Lamy A, Whitlock R, LeManach Y, Roshanov PS, McGillion M, Kavsak P, McQueen MJ, Thabane L, Rodseth RN, Buse GAL, Bhandari M, Garutti I, Jacka MJ, Schunemann HJ, Cortes OL, Coriat P, Dvirnik N, Botto F, Pettit S, Jaffe AS, Guyatt GH. Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery. JAMA. 2017 Apr 25;317(16):1642-1651. doi: 10.1001/jama.2017.4360.

    PubMed 28444280

  • Sessler DI, Meyhoff CS, Zimmerman NM, Mao G, Leslie K, Vasquez SM, Balaji P, Alvarez-Garcia J, Cavalcanti AB, Parlow JL, Rahate PV, Seeberger MD, Gossetti B, Walker SA, Premchand RK, Dahl RM, Duceppe E, Rodseth R, Botto F, Devereaux PJ. Period-dependent Associations between Hypotension during and for Four Days after Noncardiac Surgery and a Composite of Myocardial Infarction and Death: A Substudy of the POISE-2 Trial. Anesthesiology. 2018 Feb;128(2):317-327. doi: 10.1097/ALN.0000000000001985.

    PubMed 29189290

  • Rodseth RN, Biccard BM, Le Manach Y, Sessler DI, Lurati Buse GA, Thabane L, Schutt RC, Bolliger D, Cagini L, Cardinale D, Chong CP, Chu R, Cnotliwy M, Di Somma S, Fahrner R, Lim WK, Mahla E, Manikandan R, Puma F, Pyun WB, Radovic M, Rajagopalan S, Suttie S, Vanniyasingam T, van Gaal WJ, Waliszek M, Devereaux PJ. The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: a systematic review and individual patient data meta-analysis. J Am Coll Cardiol. 2014 Jan 21;63(2):170-80. doi: 10.1016/j.jacc.2013.08.1630. Epub 2013 Sep 26.

    PubMed 24076282

  • Duceppe E, Parlow J, MacDonald P, Lyons K, McMullen M, Srinathan S, Graham M, Tandon V, Styles K, Bessissow A, Sessler DI, Bryson G, Devereaux PJ. Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management for Patients Who Undergo Noncardiac Surgery. Can J Cardiol. 2017 Jan;33(1):17-32. doi: 10.1016/j.cjca.2016.09.008. Epub 2016 Oct 4.

    PubMed 27865641

  • Reiterer C, Kabon B, Taschner A, Graf A, Adamowitsch N, Horvath K, Emler D, Zotti O, Hantakova N, Hochreiter B, Fraunschiel M, Clement T, Fleischmann E. Levosimendan for postoperative subclinical heart failure after noncardiac surgery: a randomized, double-blinded, phase III trial. Nat Commun. 2025 Jul 1;16(1):5847. doi: 10.1038/s41467-025-60601-y.

    PubMed 40593481

  • Reiterer C, Kabon B, Taschner A, Adamowitsch N, Graf A, Fraunschiel M, Horvath K, Kuhrn M, Clement T, Treskatsch S, Berger C, Fleischmann E. 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. BMJ Open. 2022 Jan 21;12(1):e058216. doi: 10.1136/bmjopen-2021-058216.

    PubMed 35063963

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Levosimendan in people with Cardiovascular Risk Factor, run by Medical University of Vienna at 1 site in Austria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Postoperative maximum NT-proBNP concentration (time frame: First 5 Postoperative Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04329624, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in