LANdiolol to Avoid TAchycardia in Patients at Risk for Cardiovascular Events Undergoing Major Non-cardiac Surgery

Not Applicable

Not yet recruiting

• Conditions: Perioperative Myocardial Injury; Major Surgery; Myocardial Injury After Non-cardiac Surgery; Autonomic Dysfunction; Cardiovascular (CV) Risk; Beta Blocker
• Interventions: Drug: Landiolol

• Registration Number: NCT07168421
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

Brief Summary

Limiting perioperative tachycardia (aiming for a heart rate \<90 beats per minute throughout the perioperative period) using the ultra-short acting beta-blocker landiolol in patients with cardiovascular risk factors undergoing major surgery might lower the incidence of perioperative myocardial injury. Feasibility of the intervention needs to be proven prior to conduction of a larger trial.

Detailed Description

Despite advances in surgical and anaesthetic techniques, perioperative mortality remains high, even in developed countries. Major complications contributing almost half of all deaths after surgery are major bleeding (17%), myocardial injury after non-cardiac surgery (13%) and sepsis (12%). Myocardial injury after non-cardiac surgery occurs up to 18% in patients \>45 years and is associated with a marked increase in 30-day mortality. Additional factors posing patients at risk for perioperative myocardial injury might be autonomic dysfunction, measured as exaggerated heart rate response to exercise or impaired heart rate recovery thereafter, as perioperative tachycardia is associated with perioperative myocaridal injury. The perioperative use of beta-blockers remains controversial, but the newely marketed ultra-short acting and highly cardioselective beta-blocker landiolol offers the opportunity to reduce perioperative heart rate without affecting blood pressure. The intervention (perioperative reduction of heart rate using landiolol) in this specific patient population needs to be proven as feasible prior to conducting a larger scale trial.

Study Timeline

• Study First Submitted: 2025-08-11
• Status Verified: 2025-09
• Study First Submitted QC: 2025-09-09
• Last Update Submitted: 2025-09-09
• Study First Posted: 2025-09-11
• Last Update Posted: 2025-09-11
• Study Start: 2025-10-01
• Primary Completion: 2028-01-31
• Study Completion: 2028-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 114

Inclusion Criteria

• Patients undergoing elective non-cardiac surgery defined as intermediate or high-risk by the 2022 european society of cardiology (ESC) guidelines

• expected duration of surgery of at least 90 minutes;

• expected length of hospital stay ≥ 24 hours;

• age > 45 years with at least two of the following risk factors (adapted from revised cardiac risk index):

  • ischemic heart disease (history of myocardial infarction or positive exercise test, current complaint of chest pain considered to be secondary to myocardial ischemia, use of nitrates, pathological Q waves, prior coronary revascularization);
  • history of congestive heart failure;
  • history of cerebrovascular disease;
  • insulin-dependent diabetes mellitus;
  • creatinine > 176.8 mmol/l;
  • pre-operative NTproBNP > 200 pg/ml;

• excessive sympathetic outflow as proven by exercise testing:

  • impaired HR recovery (≤ 12 bpm within 1 minute after cessation of exercise); OR
  • exaggerated HR response (≥ 12 bpm after 1 minute of unloaded pedalling);

Exclusion Criteria

• unable to consent or follow study procedures;
• absolute contraindications for exercise testing;
• pregnancy or intention to become pregnant;
• active cardiac conditions (such as unstable coronary syndromes, decompensated heart failure, significant arrhythmias, severe valvular disease);
• urgent / emergency surgery;
• already on β-blocker (within the last 30 days prior to recruitment);
• contraindication for β-blocker therapy (bradycardia (HR < 55 bpm), hypotension (systolic blood pressure < 100 mmHg), severe peripheral vascular disease, severe asthma, allergy, higher-degree atrioventricular block);
• severe preoperative anaemia (haemoglobin < 100 g/L) unless there is a plan set up and followed for correction prior to surgery;
• planned intermediate care or intensive care admission;
• prior enrolment in this trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Landiolol	Landiolol	Landiolol will be titrated to keep heart rate below 90 beats per minute during surgery after exclusion of other factors possibly causing tachycardia (such as hypovolaemia or pain). Mean arterial pressure will be kept above 65 millimeters of mercury.

Primary Outcome Measures

Name	Time	Method
Time perioperative heart rate in target range	From induction of anaesthesia until discharge from postanaesthetic care unit [percent of time heart rate within target range (<90 beats per minute)]	As a marker of successful intervention, time perioperative heart rate in target range (below 90 beats per minute) will serve as primary outcome. The intervention is considered feasible if the heart rate stays at least 90% of the time within the target range during the perioperative period.

Secondary Outcome Measures

Name	Time	Method
Perioperative heart rate	From induction of anaesthesa until discharge from postanaesthetic care unit [heart rate in beats per minute * minutes ]	Perioprative heart rate will be calculated as time weighted area under the curve for the perioperative period.
Dose of vasopressors	Induction of anaesthesia until discharge from postanaeshetic care unit [mcg per recorded drug]	Total dose of vasopressors such as noradrenalin, ephedrine or phenylephrine will be recorded in micrograms.
Length of postanaesthetic care unit stay	Admission to postanaesthetic care unit until discharge from postanaesthetic care unit [minutes]	Lenght of postaenaesthetic care unit stay will be recorded in minutes.
Length of hospital stay	Admission to hospital until discharge from hospital [days]	Length of hospital stay will be recorded in days.
Perioperative myocardial injury	72 hours after surgery	Perioperative myocardial injury (PMI) is defined as an increase of hsTroponinT ≥ 14ng/L above the preoperative value according to the Basel-PMI criteria, not meeting major adverse cardiovascular event (MACE) criteria.

Trial Locations

Locations (1)

Bern University Hospital, Freiburgstrasse; 🇨🇭 Bern, Switzerland