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

Centre Hospitalier Universitaire, Amiens

Status and phase: Enrolling; Phase 3

Conditions: Tachycardia; Septic Shock; Mortality During Septic Shock; Beta-blocker

Treatments: Drug: Landiolol; Other: echocardiography

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT04748796

PI2020_843_0057

Details and patient eligibility

About

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.

Enrollment: 360 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• Patients with inclusion criteria already present for more than 36 hours
• Patient treated with Dobutamine, adrenaline or isoprenaline
• Patient currently treated with beta blockers (previous home betablocker treatment is not an exclusion criteria)
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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360 participants in 2 patient groups

Experimental group

Experimental group

Description:

2 days with landiolol IV + usual care

Treatment:

Drug: Landiolol

Control group

Active Comparator group

Description:

usual care according to the attending physician and following the guidelines of surviving sepsis campaign.

Treatment:

Other: echocardiography