Landiolol in Mitral Valve Surgery (LUNA)

December 19, 2025 updated by: Giovanni Landoni, Università Vita-Salute San Raffaele

The Use of Landiolol in Mitral Valve sUrgery: a raNdomized, Controlled, Double-blind triAl (LUNA)

Chronic mitral regurgitation is the most common valvular abnormality worldwide, it occurs in 10% of the general population and its prevalence increases with age. When left untreated, it can lead to left ventricular dysfunction and cause disabling symptoms (e.g., fatigue and dyspnea), life-threatening complications (e.g., ventricular dilation, congestive heart failure) and death. Surgical correction of chronic mitral regurgitation before irreversible changes happen can be curative. Open surgical valve repair or replacement are accomplished through cardiopulmonary bypass and cardioplegic arrest. Myocardial protection is essential to guarantee an uneventful perioperative course since a not-well protected heart may lead to postoperative low-cardiac output syndrome. This occurs in 30% of high-risk patients who undergo elective cardiac surgery and is associated with 20% mortality. Cardioplegia preserves the heart during ischemic arrest by reducing its metabolic demand. The most effective cardioplegia for protection in adult cardiac surgery remains unknown and improving the protection of the heart during the ischemic arrest may potentially improve patients' postoperative outcomes. Pharmacological adjuvants to the cardioplegic solutions have been tested to mitigate the ischaemic-reperfusion injury following cardiac surgery. Ultra-short acting beta-blockers (e.g., esmolol, landiolol) decrease intraoperative myocardial metabolic demand and suppress the sympathetic response to surgical stimuli while exhibiting limited adverse effects. Few studies with limited sample size investigated the role of ultra-short acting beta-blockers in reducing perioperative ischaemia and arrhythmia after cardiac surgery. When ultra-short acting beta-blockers were administered before aortic cross-clamping and as cardioplegia adjuvant we observed a trend towards a reduction in postoperative low-cardiac output syndrome (13/98 vs 6/102; p=0.08) and in the rate of hospital re-admission at one year (26/95 v 16/96, p=0.08) with an increase in the number of patients with ejection fraction >60% at hospital discharge (4/95 vs 11/92, p=0.06) (Zangrillo 2021). However, despite a growing body of literature exploring the role of ultra-short acting beta-blockers in enhancing myocardial protection during on-pump cardiac surgery, further high-quality evidence is needed before this practice can be established as standard routine care. Hence, we designed a randomized, placebo-controlled trial involving 1500 patients undergoing open mitral valve surgery to assess the effect of administering landiolol as cardioplegia adjuvant to reduce the occurrence of postoperative low-cardiac output syndrome. Successful results would have a significant impact on short and long-term complications.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1500

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Italy
      • Alessandria, Italy
      • Catania, Italy, 95123
        • Recruiting
        • Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco"
        • Contact:
      • Florence, Italy
      • Foggia, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia
        • Contact:
      • Genova, Italy
        • Recruiting
        • IRCCS San Martino di Genova
        • Contact:
      • Milan, Italy, 20132
        • Recruiting
        • Ospedale San Raffaele
        • Contact:
        • Contact:
        • Principal Investigator:
          • Fabrizio Monaco, MD
      • Milan, Italy
      • Palermo, Italy
      • Pisa, Italy
      • Potenza, Italy
      • Ravenna, Italy
        • Recruiting
        • Maria Cecilia Hospital S.p.A.
        • Contact:
    • Piedmont
      • Alessandria, Piedmont, Italy, 15121
    • TO
      • Torino, TO, Italy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Older than 18 years;
  • Elective mitral valve repair or replacement surgery with planned cardiopulmonary bypass via midline sternotomy or minithoracotomy;
  • Preoperative evidence of left ventricular end-systolic diameter >40 mm and/or left ventricular end-diastolic diameter >60 mm and/or left ventricular ejection fraction<60%;
  • Signed informed consent.

Exclusion Criteria:

  • Need for preoperative dialysis;
  • Hepatic dysfunction (defined as Child-Pugh class C);
  • History of previous unusual response to beta-blockers;
  • Urgent or emergency surgery;
  • Patient already in need of mechanical circulatory support before surgery (except for IABP);
  • Pregnancy as documented by a pregnancy test performed in the last 72h before surgery;
  • Patients with preoperative evidence of hypernatremia (serum sodium concentration: > 160 mmol/L);
  • Patients with preoperative evidence of hyperchloremia (serum chloride concentration: >115 mmol/L);
  • Patients with hypersensitivity to the active substance or to any of the excipients;
  • Patients with severe bradycardia (less than 50 beats per minute) sick sinus syndrome, severe atrioventricular nodal conductance disorders or 2nd -3rd degree atrioventricular block and without a pacemaker;
  • Patients with cardiogenic shock, severe hypotension (MAP<50 mmHg), decompensated heart failure or severe pulmonary hypertension (PAPs >70 mmHg);
  • Patients with non-treated phaeochromocytoma;
  • Patients with acute asthmatic attack;
  • Patients with severe, uncorrectable metabolic acidosis.
  • Participation in a clinical trial in which an investigational drug was administered within 30 days of screening or within the 5 half-lives of the study drug, whichever is longer.
  • Planned use of ultra-short acting beta-blockers as intraoperative cardiac protective strategy.
  • Refusal or inability to sign the informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Landiolol
intraoperative landiolol, first as low-dose continuous infusion (5 mcg/kg/min) until aortic cross clamping, followed by an intravenous bolus (0.3 mg/kg) after aortic cannulation (but still before aortic cross-clamping) and a further intravenous bolus dose of 0.3 mg/kg as cardioplegia adjuvant added to the first administered cardioplegic solution.
Drug: Landiolol
Intravenous infusion of landiolol
Placebo Comparator: Placebo
intraoperative equivolume placebo normal saline solution, first as low-dose continuous infusion until aortic cross clamping, followed by an intravenous bolus after aortic cannulation and a further equivolume quantity added to the first administered cardioplegic solution.
Drug: Placebo
Intravenous infusion of saline solution of NaCl 0.9%

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Reduction of the occurrence of postoperative low-cardiac output syndrome (LCOS)
Time Frame: Until ICU discharge, an average of 4 days

The primary outcome will be the reduction of the occurrence of postoperative low-cardiac output syndrome, defined following Cholley et al. 2017 JAMA as the presence of at least one of the following:

  1. need of prolonged catecholamine infusion (persisting beyond 48 hours after the initiation of the study drug);
  2. need of circulatory mechanical assist devices in the postoperative period (if an intra-aortic balloon pump was inserted preventively, the criteria will be met if patients are not weaned from the balloon within 96 hours);
  3. need for renal replacement therapy at any time during the intensive care unit stay.
Until ICU discharge, an average of 4 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Death
Time Frame: 1 year
1 year
Patients requiring prolonged (>48 h) catecholamine infusion
Time Frame: Until ICU discharge, an average of 4 days
Until ICU discharge, an average of 4 days
Patients with increased postoperative cardiac biomarkers (Troponin I or T)
Time Frame: Up to 48 hours.
Up to 48 hours.
Patients with a reduction in left ventricular ejection fraction
Time Frame: Until hospital discharge, an average of 10 days
Until hospital discharge, an average of 10 days
Number of patients readmitted to hospital for cardiac reasons
Time Frame: 1 year
1 year
EQ-5D-5L questionnaire
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Università Vita-Salute San Raffaele

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 28, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 15, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 27, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 29, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 19, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PNRR-MCNT2-2023-12377946

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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