Clinical trial NCT04931225: LANdiolol MIcrocirculatory Effects During Septic chOc (MILANOS)
Official title: LANdiolol MIcrocirculatory Effects During Septic chOc
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Septic Shock
Keywords: Septic shock
Landiolol
Microcirculatory effects
Heart rate
Hemodynamic effects
Microvascular reactivity
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-06-18
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rate of decrease in heart rate (HR) on microcirculatory vascular reactivity
timeFrame: 24 hours
Secondary outcomes:
measure: Cardiac flow
timeFrame: 24 hours
measure: marbling score
timeFrame: 24 hours
measure: skin recoloration time
timeFrame: 24 hours
measure: Arterial lactate clearance
timeFrame: 24 hours
measure: Measure of Systemic and endothelial inflammation parameters
timeFrame: 24 hours
Other outcomes:
Locations:
city: Paris
country: France
facility: Intensive care department, Hôpital Saint Antoine
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Hafid AIT-OUFELLA, Professor
role: PRINCIPAL_INVESTIGATOR
References: