Landiolol in Postoperative Atrial Fibrillation

Study Overview
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Brief Summary
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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.

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

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Landiolol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Landiolol group<br>Landiolol perfusion in incremental doses (range 0.5 to 10 µg/kg/min) over 2 hours | Drug: Landiolol<br>* Landiolol perfusion over 120 minutes in incremental doses : 0.5, 1, 2, 5 and 10 µg/kg/min. Doses are modified every 20 minutes<br>|
| Placebo Comparator: Placebo group<br>Placebo perfusion in incremental doses (range 0.03 to 0.6 mL/kg/h) over 2 hours | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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landiolol, microcirculation, cardiac surgery, atrial fibrillation