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

Official title

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

Overview

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.

Interventions

• Drug Landiolol
  The main dose range is 1-40 mcg/kg/min, titrated to the effect on heart rate aiming for a heart rate of below 90 beats per minute throughout. This dose can be decreased to 0 if heart rate stays below target.

Primary outcome measures

• Time perioperative heart rate in target range [Time frame: From induction of anaesthesia until discharge from postanaesthetic care unit [percent of time heart rate within target range (<90 beats per minute)]]

Secondary outcome measures (5)

• Perioperative heart rate [Time frame: From induction of anaesthesa until discharge from postanaesthetic care unit [heart rate in beats per minute * minutes ]]
• Dose of vasopressors [Time frame: Induction of anaesthesia until discharge from postanaeshetic care unit [mcg per recorded drug]]
• Length of postanaesthetic care unit stay [Time frame: Admission to postanaesthetic care unit until discharge from postanaesthetic care unit [minutes]]
• Length of hospital stay [Time frame: Admission to hospital until discharge from hospital [days]]
• Perioperative myocardial injury [Time frame: 72 hours after surgery]

Eligibility criteria

Inclusion criteria

• Patients undergoing elective non-cardiac surgery defined as intermediate or high-risk by the 2022 european society of cardiology (ESC) guidelines
• surgery performed under general anesthesia;
• expected length of hospital stay ≥ 24 hours;
• age ≥ 45 years;
• at least two of the following risk factors:

• age ≥ 75 years
• arterial hypertension;
• 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;
• peripheral artery disease;
• diabetes mellitus;
• GFR ≤ 59 ml/min pro 1.73 m2;
• pre-operative NTproBNP > 200 pg/ml;
• excessive sympathetic outflow as proven by exercise testing:

• impaired heart rate recovery (≤ 12 bpm within 1 minute after cessation of exercise); OR
• exaggerated heart rate response (≥ 12 bpm after 3 minutes 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

Switzerland · 1 center

• Bern University Hospital, Freiburgstrasse — Bern

Identifiers

NCT: NCT07168421 · BECD-1-21

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗