Landiolol for heart rate control in patients with septic shock and persistent tachycardia A multicenter Randomized Clinical Trial (Landi-SEP)

Abstract Purpose Excessive tachycardia in resuscitated septic shock can impair hemodynamics and worsen patient outcome. We asked whether heart rate (HR) control can be achieved without increased vasopressor requirements by using a titrated 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 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% 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 betablocker landiolol was effective in reducing and maintaining HR without increasing vasopressor requirements after 24 h in patients with septic shock and persistent tachycardia. Mortality rates and safety were comparable to standard treatment alone. TRIAL REGISTRATION: EU Clinical Trial Register; EudraCT Number: 2017-002138-22