LANdiolol MIcrocirculatory Effects During Septic chOc (MILANOS)

Assistance Publique - Hôpitaux de Paris

Status and phase

Enrolling

Phase 3

Conditions

Septic Shock

Treatments

Drug: Landiolol

Study type

Interventional

Funder types

Other

Identifiers

NCT04931225

APHP191047

Details and patient eligibility

About

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.

Full 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.

Enrollment

44 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No 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