LANdiolol MIcrocirculatory Effects During Septic chOc (MILANOS)

Septic Shock Clinical Trial

— MILANOS  

Official title:

LANdiolol MIcrocirculatory Effects During Septic chOc

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04931225
• Other study ID #: APHP191047
• Status: Recruiting
• Phase: Phase 3
• Start date: July 18, 2022
• Est. completion date: January 2024

Study information

• Verified date: October 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Hafid AIT-OUFELLA, Professor
• Phone: 01 49 28 23 15
• Email: hafid.aitoufella[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Septic Shock
• Shock, Septic

Intervention

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.

Locations

Country	Name	City	State
France	Intensive care department, Hôpital Saint Antoine	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cardiac flow	Measure of the cardiac flow to evaluate the hemodynamic effects of Landiolol vs. usual tachycardia management	24 hours
Secondary	marbling score	Measure of the marbling score to evaluate the effects of Landiolol vs. usual tachycardia management	24 hours
Secondary	skin recoloration time	Measure of skin recoloration time to evaluate the effects of Landiolol vs. usual tachycardia management	24 hours
Secondary	Arterial lactate clearance	Measure of sarterial lactate clearance to evaluate the effects of Landiolol vs. usual tachycardia management	24 hours
Secondary	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