Landiolol in patients with septic shock resident in an intensive care unit (LANDI-SEP): study protocol for a randomized controlled trial

Abstract

BackgroundIn patients with septic shock, the presence of an elevated heart rate (HR) after fluid resuscitation marks a subgroup of patients with a particularly poor prognosis. Several studies have shown that HR control in this population is safe and can potentially improve outcomes. However, all were conducted in a single-center setting. The aim of this multicenter study is to demonstrate that administration of the highly beta1-selective and ultrashort-acting beta blocker landiolol in patients with septic shock and persistent tachycardia (HR ≥ 95 beats per minute [bpm]) is effective in reducing and maintaining HR without increasing vasopressor requirements.MethodsA phase IV, multicenter, prospective, randomized, open-label, controlled study is being conducted. The study will enroll a total of 200 patients with septic shock as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria and tachycardia (HR ≥ 95 bpm) despite a hemodynamic optimization period of 24–36 h. Patients are randomized (1:1) to receive either standard treatment (according to the Surviving Sepsis Campaign Guidelines 2016) and continuous landiolol infusion to reach a target HR of 80–94 bpm or standard treatment alone. The primary endpoint is HR response (HR 80–94 bpm), the maintenance thereof, and the absence of increased vasopressor requirements during the first 24 h after initiating treatment.DiscussionDespite recent studies, the role of beta blockers in the treatment of patients with septic shock remains unclear. This study will investigate whether HR control using landiolol is safe, feasible, and effective, and further enhance the understanding of beta blockade in patients with septic shock.Trial registrationEU Clinical Trials Register; EudraCT, 2017-002138-22. Registered on 8 August 2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-3024-6) contains supplementary material, which is available to authorized users.

Effect of landiolol on sex-related transcriptomic changes in the myocardium during sepsis

“…Finally, data on sex dimorphism in the response to landiolol during septic cardiomyopathy should be considered in patient studies, in conjunction with an investigation of inflammation attenuation, improved outcome and heart rate control [39–42].…”

<p>Evaluating the Therapeutic Efficacy and Safety of Landiolol Hydrochloride for Management of Arrhythmia in Critical Settings: Review of the Literature</p>

“…77,78 An on-going RCT is currently using landiolol for sepsis patients has set the primary endpoint as HR response (HR = 80-94 bpm) and maintenance without increases in vasopressor requirement was observed during the first 24 h after administration. 79 From these results of animal studies and clinical reports, use of landiolol for sepsis reveals the therapeutic effect of rate control during sepsis and a subsequent beneficial effect for other vital organs.…”

Acute rate control in atrial fibrillation: an urgent need for the clinician

“… 86 , 87 There are several case reports of successful management of high rate AF in septic patients, using landiolol 86 , 88 and an ongoing RCT on this subject. 89 The potential use of landiolol in this scenario is of particular interest, as mortality and complication rate in sepsis are still high.…”