Landiolol for Prevention of Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery

NCT05084118 | Unknown Phase 3 DMC

• 1 other identifier: LAN_POAF_01
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

Brief Summary

Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery with incidences ranging from 20% to 40% with the consequence of increasing mortality, morbidity, and hospital length of stay, as well as increasing the costs to the health care system. To prevent POAF the use of beta-blockers is suggested by the EACTA and ESC guidelines. Despite the prophylactic use, the discontinuation of beta-blockers in the perioperative period is a known risk factor that contributes to the occurrence of POAF. Due to the short half time and the highly beta-1-selective properties of Landiolol, it could be possible to initiate a betablocker for prevention in the immediate postoperative setting, without adverse effects like hypotension or severe bradycardia as seen with other betablockers like Metoprolol or even sometimes Esmolol. Landiolol is already approved for the treatment of atrial tachycardias but is not yet approved for the use of prevention of POAF. In multiple previous studies the preventive potential of Landiolol in cardiac surgery could be proven in japanese study populations, with limitations due to limited sample sizes. In these trials the use of low-dose Landiolol effectively reduced the incidence of POAF without significant differences of increased side effects or in the hemodynamic stability compared to the placebo or standard of care groups. The primary objective of this prospective, double-blind, randomized, placebo-controlled phase III trial is to prove that the postoperative application of low-dose Landiolol significantly reduces the incidence of POAF without increased adverse events or hemodynamic instability compared to the placebo group after cardiac surgery in a non-Asian population.

Conditions

Atrial Fibrillation; Postoperative Complications

Keywords

landiolol

Outcome Measures

Primary Outcomes (1)

• The primary end point is a combined endpoint consisting of the occurrence of atrial fibrillation and mortality during the initial 72 hours period after surgery

  Death from any reason or the occurence of atrial in the holter ecg within 3 days after operation.

  3 days

Secondary Outcomes (9)

• Incidence/ frequency of occurrence of atrial fibrillation during the first seven days after cardiac surgery

  7 days

• Hemodynamic stability during treatment with IMP

  7 days

• Length of ICU stay

  30 days

• Requirement of intensive respiratory and circulatory support

  30 days

• Peri- and postoperative mortality

  30 days

Study Arms (2)

Landiolol group

ACTIVE COMPARATOR

Randomized patients receiving low dose landiolol after cardiac surgery

Drug: Landiolol HCl

Placebo group

PLACEBO COMPARATOR

Randomized patients receiving 0,9% saline solution after cardiac surgery

Drug: Placebo

Interventions

Landiolol HCl DRUG

continous 2mcg/kg/min low dose application of Landiolol HCl for 72 hours

Also known as: Rapibloc

Landiolol group

Placebo DRUG

continous application of isotone saline solution for 72 hours

Also known as: Isotone saline solution

Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years old
• Written informed consent from patient
• Patients are in sinus rhythm
• Oral Betablocker in the patients long-term medication
• One of the following cardiac surgical procedures which is planned on cardiopulmonary bypass (CPB):
• Single valve surgery
• Single or multiple CABG procedures
• Single valve surgery in combination with one or multiple coronary artery bypass grafts (CABGs)
• Multiple valve surgery in combination with or without CABG
• Single or multiple valve surgery in combination with ascending aorta procedure with or without additional CABG
• Re-surgery of aortic valve, mitral valve, aortic arch or ascending aorta with or without CABG
• Cardiac surgery is performed electively

You may not qualify if:

• Bodyweight \> 101kg and/or BMI ≥ 40
• Cardiac surgery is planned as minimally invasive procedure (e.g., without thoracotomy or with lateral incision, minimal thoracotomy) or planned as off-pump surgery
• Planned maze procedure, radiofrequency ablation, pulmonary vein ablation, resection of the atrial appendix or atrial resections during the surgery
• Sinus bradycardia (resting heart rate \< 50/min) at screening and before start of IMP treatment
• Second- or third-degree atrioventricular block at screening and before start of IMP treatment
• Clinical hypothyroidism or hyperthyroidism at screening
• History of ventricular arrhythmia
• Permanent atrial fibrillation or atrial fibrillation at time of screening and IMP administration
• Emergency cardiac surgery
• Requiring inotropic, vasopressor or requiring ventilatory support at time of screening
• Circulatory shock requiring mechanical circulatory support before initiation of study medication
• Distributive shock (cardiac index\>2.2 L/min with norepinephrine dose \> 0.3 µg/kg/min to reach mean arterial pressure \> 65mmHg) before initiation of study medication
• More than 5 units of RBC necessary to maintain a haemoglobin level \>8mg/dl at the end of surgery
• Prior cardiac surgery within the past 6 months
• History of heart transplantation or planned heart transplantation

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

University Hospital Vienna

Vienna, 1090, Austria

RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation; Postoperative Complications

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Andreas Binder

  Medical University of Vienna, Division of Cardiothoracic and Vascular Anesthesia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andreas Binder

CONTACT

0043 1 40400 64100; andreas.binder@meduniwien.ac.at

Barbara Steinlechner

CONTACT

0043 1 40400 41850; barbara.steinlechner@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: October 19, 2021
• Study Start: October 21, 2021
• Primary Completion: November 1, 2023
• Study Completion: June 1, 2024
• Last Updated: October 22, 2021

Record last verified: 2021-10

Locations

AU (1)