LANdiolol MIcrocirculatory Effects During Septic chOc (MILANOS)
- Registration Number
- NCT04931225
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 44
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Sinus tachycardia not compensatory, if the doctor considers that the heart rate acceleration should be treated.
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The study will be carried out in
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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.
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Age >18 years
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Patient (or family member) informed consent signature or emergency consent
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Affiliation to a social security system
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Landiolol injection 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.
- Primary Outcome Measures
Name Time Method Rate of decrease in heart rate (HR) on microcirculatory vascular reactivity 24 hours 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
Name Time Method Arterial lactate clearance 24 hours Measure of sarterial lactate clearance to evaluate the effects of Landiolol vs. usual tachycardia management
Measure of Systemic and endothelial inflammation parameters 24 hours 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)
Cardiac flow 24 hours Measure of the cardiac flow to evaluate the hemodynamic effects of Landiolol vs. usual tachycardia management
marbling score 24 hours Measure of the marbling score to evaluate the effects of Landiolol vs. usual tachycardia management
skin recoloration time 24 hours Measure of skin recoloration time to evaluate the effects of Landiolol vs. usual tachycardia management
Trial Locations
- Locations (1)
Intensive care department, Hôpital Saint Antoine
🇫🇷Paris, France