The use of Landiolol in mitral valve sUrgery: a raNdomized, controlled, double-blind triAl. (LUNA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale San Raffaele S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

28 Jan 2025 → ongoing

Decision date (initial)

2024-11-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministry of Health – Directorate-General for Health Research and Innovation - PNRR2023

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the effect of administering landiolol as cardioplegia adjuvant to reduce the occurrence of postoperative low-cardiac output syndrome.

Secondary objectives 6

1. To assess the expected cardiac protective effects of landiolol in terms of prolonged (>48 h) infusion of catecholamines.
2. To assess the expected cardiac protective effects of landiolol in terms of postoperative peak of cardiac biomarkers (Troponin I or T).
3. To assess the expected cardiac protective effects of landiolol in terms of left ventricular ejection fraction.
4. To assess the expected cardiac protective effects of landiolol in terms of need for new admission to hospital for cardiac reasons.
5. To assess the expected cardiac protective effects of landiolol in terms of quality of life.
6. To assess the expected cardiac protective effects of landiolol in terms of mortality.

Conditions and MedDRA coding

Low-cardiac output syndrome (LCOS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Older than 18 years;
2. Undergoing elective mitral valve repair or replacement surgery with planned cardiopulmonary bypass via midline sternotomy or minithoracotomy;
3. 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%;
4. Signed informed consent.

Exclusion criteria 16

1. Need for preoperative dialysis;
2. Hepatic dysfunction (defined as Child-Pugh class C);
3. History of previous unusual response to beta-blockers;
4. Urgent or emergency surgery;
5. Patient already in need of mechanical circulatory support before surgery (except for IABP);
6. Pregnancy as documented by a pregnancy test performed in the last 72h before surgery
7. Refusal or inability to sign the informed consent.
8. Patients with preoperative evidence of hypernatremia (serum sodium concentration: > 160 mmol/L);
9. Patients with preoperative evidence of hyperchloremia (serum chloride concentration: >115 mmol/L);
10. Patients with hypersensitivity to the active substance or to any of the excipients;
11. 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;
12. Patients with cardiogenic shock, severe hypotension (MAP<50 mmHg), decompensated heart failure or severe pulmonary hypertension (PAPs >70 mmHg);
13. Patients with non-treated phaeochromocytoma;
14. Patients with acute asthmatic attack;
15. Patients with severe, uncorrectable metabolic acidosis.
16. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. The primary outcome will be the reduction of the occurrence of postoperative low-cardiac output syndrome, defined following a recent JAMA publication (Cholley 2017) as the presence of at least one of the following:
2. need of prolonged catecholamine infusion (persisting beyond 48 hours after the initiation of the study drug);
3. need of circulatory mechanical assist devices in the postoperative period (if an intraaortic balloon pump was inserted preventively, the criteria will be met if patients are not weaned from the balloon within 96 hours);
4. need for renal replacement therapy at any time during the intensive care unit stay.

Secondary endpoints 6

1. Patients requiring prolonged (>48 h) catecholamine infusion;
2. patients with increased postoperative cardiac biomarkers (Troponin I or T);
3. patients with a reduction in left ventricular ejection fraction;
4. number of patients readmitted to hospital for cardiac reasons;
5. EQ-5D-5L questionnaire;
6. death.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale San Raffaele S.r.l.

Sponsor organisation

Ospedale San Raffaele S.r.l.

Address

Via Olgettina 60

City

Milan

Postcode

20132

Country

Italy

Scientific contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Fabrizio Monaco

Public contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Fabrizio Monaco

Locations

1 EU/EEA country · 35 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications