RecruitingPhase 3NCT04748796

Comparison of Landiolol Versus Standard of Care for Prevention of Mortality in Patients Hospitalized for a Septic Shock With Hypercontractility

Comparison of Landiolol Versus Standard of Care for Prevention of Mortality in Patients Hospitalized for a Septic Shock With Hypercontractility: an Open Label Prospective Randomized Study

Sponsor

Centre Hospitalier Universitaire, Amiens

Enrollment

360 participants

Start Date

Feb 1, 2021

Study Type

INTERVENTIONAL

Conditions

Septic Shock Tachycardia Mortality During Septic Shock Beta-blocker

Summary

Several data emphasize the relation between tachycardia (\>90/min) and high mortality during septic shock. The investigators previously demonstrated the high mortality associated with hypercontractility, tachycardia and the presence of a left ventricular obstruction. A severe hypovolemia, a hyper adrenergic stimulation or a severe vasoplegia can all explain this relation between tachycardia, hypercontractility and the mortality during septic shock. Landiolol is another short-term acting beta-blocker with a half-life of 4 minutes without any beta 2 activity or membrane stabilizing effect. The landiolol has been used in critically ill patients to control supraventricular tachycardia but not in this context of tachycardia and septic shock. The investigators hypothesize that landiolol by reducing the heart rate may improve the survival of patients treated for a septic shock and presenting with an hypercontractility state.

Eligibility

Min Age: 18 Years

Inclusion Criteria10

Age ≥ 18 years old
Patient admitted for a septic shock (according to the SEPSIS3 definition: sepsis with persisting hypotension (MAP<65mmHg or SAP <90mmHg) requiring vasopressors to maintain MAP>65mmHg and having a serum lactate level >2 mmol/L
Patient who received at least 30ml/kg of fluid and absence of fluid responsiveness
Left ventricular ejection fraction >65% (visual or Simpson method using echocardiography)
Tachycardia >100 bpm in sinus rhythm with a MAP 65mmHg for more than 1 hour
Patient receiving invasive mechanical ventilation
Patients adapted to the ventilator under sedation and analgesia
Written informed consent
Patient covered by French national health insurance
Patient treated with Dobutamine, adrenaline or isoprenaline

Exclusion Criteria21

Supra ventricular (atrial fibrillation or flutter) or ventricular arrhythmias
Patients with any form of cardiac pacing
Sick sinus syndrome
Severe atrioventricular (AV) nodal conductance disorders (without pacemaker): 2nd or 3rd degree AV block
Known pulmonary hypertension
ScVO2 <70%
Moribund
Cardiac arrest
Non-treated phaeochromocytoma
Acute asthmatic attack
Pregnant or breastfeeding woman
Patient deprived of liberty by administrative or judicial decision or placed under judicial protection (guardianship or supervision),
Age <18 years
Hypersensitivity to the active substance or to any of the excipients
Severe bradycardia (less than 50 beats per minute)
Cardiogenic shock
Severe hypotension
Decompensated heart failure when considered not related to the arrhythmia
Severe, uncorrectable metabolic acidosis
Presence of significant bleeding, or
Acute respiratory distress defined by increased oxygen dependency, polypnea > 30 /min, signs of struggle (pulling, thoraco-abdominal sway) if the patient is not intubated and ventilated.

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Interventions

OTHERechocardiography

Full echocardiography will be performed at baseline and during the follow-up at H1, H3, H6 and H12.

DRUGLandiolol

Patients randomized to the experimental group will be treated according to the standard of care plus for 2 days with landiolol IV started at a dose of 1 microgram/kg/min and progressively increased every 10 minutes to a maximum of 40 micrograms/kg/min.