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

Primary Purpose

Septic Shock

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Landiolol
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Septic Shock focused on measuring Septic shock, Landiolol, Microcirculatory effects, Heart rate, Hemodynamic effects, Microvascular reactivity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Intensive care department, Hôpital Saint AntoineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Landiolol injection

Usual tachycardia management

Arm Description

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.

No treatment, usual tachycardia management.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Cardiac flow
Measure of the cardiac flow to evaluate the hemodynamic effects of Landiolol vs. usual tachycardia management
marbling score
Measure of the marbling score to evaluate the effects of Landiolol vs. usual tachycardia management
skin recoloration time
Measure of skin recoloration time to evaluate the effects of Landiolol vs. usual tachycardia management
Arterial lactate clearance
Measure of sarterial lactate clearance to evaluate the effects of Landiolol vs. usual tachycardia management
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)

Full Information

First Posted
May 14, 2021
Last Updated
October 4, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT04931225
Brief Title
LANdiolol MIcrocirculatory Effects During Septic chOc (MILANOS)
Acronym
MILANOS
Official Title
LANdiolol MIcrocirculatory Effects During Septic chOc
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 18, 2022 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Septic Shock
Keywords
Septic shock, Landiolol, Microcirculatory effects, Heart rate, Hemodynamic effects, Microvascular reactivity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Landiolol injection
Arm Type
Experimental
Arm Description
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.
Arm Title
Usual tachycardia management
Arm Type
No Intervention
Arm Description
No treatment, usual tachycardia management.
Intervention Type
Drug
Intervention Name(s)
Landiolol
Other Intervention Name(s)
Rapibloc
Intervention Description
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.
Primary Outcome Measure Information:
Title
Rate of decrease in heart rate (HR) on microcirculatory vascular reactivity
Description
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.
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Cardiac flow
Description
Measure of the cardiac flow to evaluate the hemodynamic effects of Landiolol vs. usual tachycardia management
Time Frame
24 hours
Title
marbling score
Description
Measure of the marbling score to evaluate the effects of Landiolol vs. usual tachycardia management
Time Frame
24 hours
Title
skin recoloration time
Description
Measure of skin recoloration time to evaluate the effects of Landiolol vs. usual tachycardia management
Time Frame
24 hours
Title
Arterial lactate clearance
Description
Measure of sarterial lactate clearance to evaluate the effects of Landiolol vs. usual tachycardia management
Time Frame
24 hours
Title
Measure of Systemic and endothelial inflammation parameters
Description
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)
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hafid AIT-OUFELLA, Professor
Phone
01 49 28 23 15
Email
hafid.aitoufella@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hafid AIT-OUFELLA, Professor
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Intensive care department, Hôpital Saint Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hafid AIT-OUFELLA, Professor
Phone
01 49 28 23 15
Email
hafid.aitoufella@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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LANdiolol MIcrocirculatory Effects During Septic chOc (MILANOS)

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