Landiolol in Postoperative Atrial Fibrillation (MMELPOAF)

Microcirculatory and Macrocirculatory Effects of Landiolol in Prevention of Postoperative Atrial Fibrillation: a Randomized Study.

Postoperative atrial fibrillation is a common complication after cardiac surgery and is associated with an elevation of morbidity and mortality. The recommended treatment includes heart rate control with a beta blocker. Landiolol is a new-generation beta-blocker with favourable pharmacologic properties making an interesting drug to treat postoperative atrial fibrillation. However, Landiolol micro and macrocirculatory effects in the setting of atrial fibrillation are yet to describe. The aim of this study is to describe microcirculatory effects of incremental doses of landiolol in postoperative atrial fibrillation compared to a placebo. Our hypothesis is Landiolol will improve microcirculation disorders.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Landiolol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bron, France
    • Hôpital Louis Pradel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient underwent conventional cardiac surgery
• Age > 18 years
• Writing contentment

Exclusion Criteria:

• Pre-existing chronic atrial fibrillation
• Contraindication to beta-blockers
• Circulatory shock (cardiac index<2.2 L/min and lactate>4mmol/L)
• Distributive shock (cardiac index>2.2 L/min with norepinephrine dose > 0.3 µg/kg/min to reach mean arterial pressure > 65mmHg).
• Acute respiratory distress
• Major bleeding (>200mL/h)
• Patient already included into an interventional clinical study
• Pregnancy
• No social security insurance
• Patient not able to give consent (curators, patients deprived of public rights)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Landiolol group; Landiolol perfusion in incremental doses (range 0.5 to 10 µg/kg/min) over 2 hours	Drug: Landiolol; Landiolol perfusion over 120 minutes in incremental doses : 0.5, 1, 2, 5 and 10 µg/kg/min. Doses are modified every 20 minutes
Placebo Comparator: Placebo group; Placebo perfusion in incremental doses (range 0.03 to 0.6 mL/kg/h) over 2 hours	Drug: Placebo; Placebo perfusion is sodium chloride NaCl 0.9% over 120 minutes in incremental doses : 0.03, 0.06, 0.12, 0.3 and 0.6 mL/kg/h. Doses are modified every 20 minutes. Perfusion are similar in landiolol group to preserve blind.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)	Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.	at 20 minutes
Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)	Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.	at 40 minutes
Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)	Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.	at 60 minutes
Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)	Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.	at 80 minutes
Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)	Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.	at 100 minutes
Tissular resaturation speed measured by somatic near-infrared spectroscopy (NIRS)	Tissular resaturation speed is measured after vascular occlusion test. At each time end-point, an occlusion of the arm blood flow with a tourniquet is made. After the nadir of the tissular saturation of the arm is reached the tourniquet is released and the resaturation speed is measured using the NIRS.	at 120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microcirculatory mean flow index (MIF) acquired by sublingual microscopy		at 120 minutes
proportion of perfused vessels acquired by sublingual microscopy		at 120 minutes
functional capillary density acquired by sublingual microscopy		at 120 minutes
De Backer score acquired by sublingual microscopy		at 120 minutes
heterogeneity of the mean flow index acquired by sublingual microscopy		at 120 minutes
Heart rate	hemodynamic parameters	at 120 minutes
systolic arterial pressure	hemodynamic parameters	at 120 minutes
diastolic arterial pressure	hemodynamic parameters	at 120 minutes
cardiac output measured by transthoracic echocardiography	hemodynamic parameters	at 120 minutes
systemic vascular resistance	hemodynamic parameters	at 120 minutes
arterial elastance.	hemodynamic parameters	at 120 minutes
Ejection fraction of the left ventricle (FEVG)	echocardiographic parameters	at 120 minutes
telesystolic volumes of the right ventricle	echocardiographic parameters	at 120 minutes
telesystolic volumes of the left ventricle	echocardiographic parameters	at 120 minutes
telediastolic volumes of the right ventricle	echocardiographic parameters	at 120 minutes
telediastolic volumes of the left ventricle	echocardiographic parameters	at 120 minutes
right ventricle contractility (measured with TAPSE and tricuspid S-wave)	echocardiographic parameters	at 120 minutes
intracardiac filling pressure profiles (E/a, E/Vp, E/e')	echocardiographic parameters	at 120 minutes
oxygen consumption (V02)	tissular perfusion parameters	at 120 minutes
oxygen delivery (DO2),	tissular perfusion parameters	at 120 minutes
carbon dioxide production (VCO2)	tissular perfusion parameters	at 120 minutes
arterial lactate	tissular perfusion parameters	at 120 minutes

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Matthias Jacquet-Lagrèze, Hospices civils de Lyon

Publications and helpful links

General Publications

• Ferraris A, Jacquet-Lagreze M, Cazenave L, Fornier W, Jalalzai W, Rousseau-Saine N, Allaouchiche B, Junot S, Pozzi M, Fellahi JL; Anesthesie-Reanimation Coeur-Thorax-Vaisseaux (ARCOTHOVA) Group. Microcirculatory effects of landiolol: a double-blind, randomised, controlled study after cardiac surgery. Br J Anaesth. 2021 Jun;126(6):e212-e214. doi: 10.1016/j.bja.2021.03.013. Epub 2021 Apr 24. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2019
• Primary Completion (Actual): December 4, 2019
• Study Completion (Actual): December 4, 2019

Study Registration Dates

• First Submitted: December 14, 2018
• First Submitted That Met QC Criteria: December 14, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: cardiac surgery; atrial fibrillation; microcirculation; landiolol
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Anti-Arrhythmia Agents; Adrenergic Agents; Adrenergic beta-Antagonists; Adrenergic Antagonists; Landiolol
• Other Study ID Numbers: 69HCL16_0743; 2018-000307-17 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No