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Randomized Controlled Trial
. 2024 Oct;50(10):1622-1634.
doi: 10.1007/s00134-024-07587-1. Epub 2024 Sep 19.

Landiolol for heart rate control in patients with septic shock and persistent tachycardia. A multicenter randomized clinical trial (Landi-SEP)

Sebastian Rehberg  1 , Sandra Frank  2 , Vladimír Černý  3   4   5   6   7 , Radek Cihlář  8 , Rainer Borgstedt  9 , Gianni Biancofiore  10 , Fabio Guarracino  11 , Andreas Schober  12 , Helmut Trimmel  13 , Thomas Pernerstorfer  14 , Christian Siebers  15 , Pavel Dostál  5   7 , Andrea Morelli  16 , Michael Joannidis  17 , Ingrid Pretsch  18 , Christian Fuchs  19 , Tim Rahmel  20 , Matej Podbregar  21   22 , Éva Duliczki  23 , Kadri Tamme  24 , Martin Unger  25 , Jan Sus  25 , Christoph Klade  25 , Kurt Krejcy  25 , Nairi Kirchbaumer-Baroian  25 , Günther Krumpl  26 , František Duška  3 ; LANDI-SEP Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Landiolol for heart rate control in patients with septic shock and persistent tachycardia. A multicenter randomized clinical trial (Landi-SEP)

Sebastian Rehberg et al. Intensive Care Med. 2024 Oct.

Abstract

Purpose: Excessive tachycardia in resuscitated septic shock patients can impair hemodynamics and worsen patient outcome. We investigated whether heart rate (HR) control can be achieved without increased vasopressor requirements using the titratable highly selective, ultra-short-acting β1-blocker landiolol.

Methods: This randomized, open-label, controlled trial was conducted at 20 sites in 7 European countries from 2018 to 2022 and investigated the efficacy and safety of landiolol in adult patients with septic shock and persistent tachycardia. Patients were randomly assigned to receive either landiolol along with standard treatment (n = 99) or standard treatment alone (n = 101). The combined primary endpoint was HR response (i.e., HR within the range of 80-94 beats per minute) and its maintenance without increasing vasopressor requirements during the first 24 h after treatment start. Key secondary endpoints were 28-day mortality and adverse events.

Results: Out of 196 included septic shock patients, 98 received standard treatment combined with landiolol and 98 standard treatment alone. A significantly larger proportion of patients met the combined primary endpoint in the landiolol group than in the control group (39.8% [39/98] vs. 23.5% [23/98]), with a between-group difference of 16.5% (95% confidence interval [CI]: 3.4-28.8%; p = 0.013). There were no statistically significant differences between study groups in tested secondary outcomes and adverse events.

Conclusion: The ultra-short-acting beta-blocker landiolol was effective in reducing and maintaining HR without increasing vasopressor requirements after 24 h in patients with septic shock and persistent tachycardia. There were no differences in adverse events and clinical outcomes such as 28-day mortality vs. standard of care. The results of this study, in the context of previous trials, do not support a treatment strategy of stringent HR reduction (< 95 bpm) in an unselected septic shock population with persistent tachycardia. Further investigations are needed to identify septic shock patient phenotypes that benefit clinically from HR control.

Keywords: Heart rate control; Landiolol; Persistent tachycardia; Sepsis; Septic shock; Ultra-short-acting beta-blocker.

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Conflict of interest statement

All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. MU, JS, CK, KK, NKB are employees of AOP Orphan Pharmaceuticals GmbH. GK is a Board Director of AOP Health International Management AG.

Figures

Fig. 1
Fig. 1
Study flowchart
Fig. 2
Fig. 2
Mean (SD) profiles of HR in the titration phase (a)/during the study up to day 14 (b), Mean (SD) profiles of blood pressure in the titration phase (c)/during the Study up to day 14 (d) and Mean (SE) norepinephrine equivalent dose during the titration phase (e)/during the study up to day 14 (f). bpm beats per minute, DAP diastolic arterial pressure, SAP systolic arterial pressure, mmHg millimetre of mercury
See this image and copyright information in PMC

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