LANdiolol MIcrocirculatory Effects During Septic chOc (MILANOS) (MILANOS)

LANdiolol MIcrocirculatory Effects During Septic chOc

The objectives of this study are to evaluate the effect of continuous intravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours ) up to a 15% decrease in Heart Rate (HR) on microcirculatory vascular reactivity vs. usual tachycardia management and evaluate the hemodynamic effects of Landiolol vs. usual management in patients with septic shock.

Study Overview

• Status: Recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Landiolol

Detailed Description

This is a Phase 3, prospective, randomized, open label, evaluation of the efficacy of continuous intravenous Landiolol injection up to a 15% decrease in HR on microcirculatory vascular reactivity vs. usual tachycardia management.

Design:

A monocentric, open-label, randomised, superiority clinical trial

Sample size :

44 patients, 22 in each group

Treatments groups:

Continuous intravenous Landiolol injection ( from 0.5 to 10 µg/kg/min during 12 hours ) up to a 15% decrease in HR on microcirculatory vascular reactivity vs usual tachycardia management

Treatment duration :

24 hours

Assessement:

Landiolol (Rapibloc)'s perfusion will be started at T0 at 0.5 mcg/kg/min and increased by 0.5 mcg/kg/min every 30 minutes in order to achieve a 15% (T1) decrease in HR, within the limit of 10 mcg/kg/min. Then the dosage will be maintained for 2 hours (T2) then the drug will be stopped gradually over 2 hours.

Maximum duration of Landiolol infusion will be 12 hours.

No interim analysis is planned. Analysis will be performed at the end of the study after data review and freezing of database.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hafid AIT-OUFELLA, Professor; Phone Number: 01 49 28 23 15; Email: hafid.aitoufella@aphp.fr

Study Locations

• France
  • Paris, France, 75012
    • Recruiting
    • Intensive care department, Hôpital Saint Antoine
    • Contact: Hafid AIT-OUFELLA, Professor; Phone Number: 01 49 28 23 15; Email: hafid.aitoufella@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Sinus tachycardia not compensatory, if the doctor considers that the heart rate acceleration should be treated.
• The study will be carried out in

• reanimated and stabilized septic shock defined as:

  • Septic shock is tachycardic (HR>100/min) patients with sepsis (suspected infection + 2 SOFA points) according to the latest international definition and the need to receive noradrenaline to maintain an average blood pressure above 65 mmHg
  • Patient supported for at least 6 hours, necessary for diagnostic management and hemodynamic optimization according to international standards and for less than 24 hours to limit confounding factors related to prolonged reanimation (sedation) and empowerment of organ failure in general and vascular in particular. Hemodynamic stabilization will be defined as the absence of increased doses of norepinephrine in the previous two hours to limit the risk of hypotension induced by Landiolol infusion.
• Age >18 years
• Patient (or family member) informed consent signature or emergency consent
• Affiliation to a social security system

Exclusion Criteria:

• Asthma
• Patients treated with the following bradycardizing drugs:
• Digitalis
• Bradycardizing calcium channel blockers
• Cordarone
• Other beta-blocker
• Hypersensitivity to Landiolol or to one of its excipients (Mannitol E421, sodium hydroxide)
• Sinus disease
• Cardiogenic shock
• Decompensated heart failure when considered unrelated to arrhythmia
• Pregnant or nursing woman,
• Participation in another interventional research involving the human person or being in the exclusion period following a previous research involving the human person, if applicable
• Ward or curative patient
• Moribund patient
• Estimated life expectancy less than 1 month

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Landiolol injection; Intravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours) up to a 15% decrease in HR on microcirculatory vascular reactivity.	Drug: Landiolol; Intravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours) up to a 15% decrease in HR on microcirculatory vascular reactivity.; Other Names: Rapibloc
No Intervention: Usual tachycardia management; No treatment, usual tachycardia management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of decrease in heart rate (HR) on microcirculatory vascular reactivity	The objectives of this study are to evaluate the effect of continuous intravenous Landiolol injection (from 0.5 to 10 µg/kg/min during 12 hours ) up to a 15% decrease in HR on microcirculatory vascular reactivity vs. usual tachycardia management in patients with septic shock.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac flow	Measure of the cardiac flow to evaluate the hemodynamic effects of Landiolol vs. usual tachycardia management	24 hours
marbling score	Measure of the marbling score to evaluate the effects of Landiolol vs. usual tachycardia management	24 hours
skin recoloration time	Measure of skin recoloration time to evaluate the effects of Landiolol vs. usual tachycardia management	24 hours
Arterial lactate clearance	Measure of sarterial lactate clearance to evaluate the effects of Landiolol vs. usual tachycardia management	24 hours
Measure of Systemic and endothelial inflammation parameters	Evaluate the hemodynamic effects of Landiolol vs. usual tachycardia management on Systemic and endothelial inflammation parameters: Plasma cytokines (Procartaplex) VCAM-1 (vascular endothelial cell adhesion molecule), Soluble Endocan (ELISA)	24 hours

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Hafid AIT-OUFELLA, Professor, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2022
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): January 1, 2024

Study Registration Dates

• First Submitted: May 14, 2021
• First Submitted That Met QC Criteria: June 17, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 4, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Septic shock; Heart rate; Microcirculatory effects; Hemodynamic effects; Microvascular reactivity; Landiolol
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Shock, Septic; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Landiolol
• Other Study ID Numbers: APHP191047

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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