Landiolol in Mitral Valve Surgery

Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversità Vita-Salute San Raffaele

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

Need for preoperative dialysis;

Hepatic dysfunction (defined as Child-Pugh class C);

History of previous unusual response to beta-blockers;

Urgent or emergency surgery;

Trial design

Design model

Parallel

Treatments tested in this trial

  • Landiolol

    Drug

    Intravenous infusion of landiolol

  • Placebo

    Drug

    Intravenous infusion of saline solution of NaCl 0.9%

Treatment groups

1,500 Participants
are divided into 2 treatment groups
Group A: LandiololExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Reduction of the occurrence of postoperative low-cardiac output syndrome (LCOS)

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.

Time frame
Until ICU discharge, an average of 4 days

Secondary outcomes

1

Patients requiring prolonged (>48 h) catecholamine infusion

Time frame
Until ICU discharge, an average of 4 days
2

Patients with increased postoperative cardiac biomarkers (Troponin I or T)

Time frame
Up to 48 hours.
3

Patients with a reduction in left ventricular ejection fraction

Time frame
Until hospital discharge, an average of 10 days
4

Number of patients readmitted to hospital for cardiac reasons

Time frame
1 year

Other outcomes

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