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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Septic Shock; Tachycardia; Mortality During Septic Shock; Beta-blocker
• Intervention / Treatment: Drug: Landiolol; Other: echocardiography

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80480
    • Recruiting
    • CHU Amiens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental group; 2 days with landiolol IV + usual care	Drug: Landiolol; 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.
ACTIVE_COMPARATOR: Control group; usual care according to the attending physician and following the guidelines of surviving sepsis campaign.	Other: echocardiography; Full echocardiography will be performed at baseline and during the follow-up at H1, H3, H6 and H12.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Variation of mortality rate in landiolol group compared to control group	day 28

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire, Amiens
• Collaborators: Centre Hospitalier de Beauvais; University Hospital, Montpellier; University Hospital, Caen; Centre Hospitalier Universitaire de Nīmes; University Hospital, Brest; University Hospital, Lille; Groupe Hospitalier Pitie-Salpetriere; Hôpital Edouard Herriot; Tourcoing Hospital; Centre Hospitalier Arras; Henri Mondor University Hospital; Centre Hospitalier de Roubaix; Hospital Avicenne; Hospital Ambroise Paré Paris; Centre Hospitalier de Bethune; Centre Hospitalier de Lens; Centre Hospitalier VALENCIENNES; CH Dieppe; CH Elbeuf; CH Le Havre; CH COMPIEGNE; CH Laon; CH Cherbourg; CH Douai; CH Montreuil; CH Lomme; CH Calais

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2021
• Primary Completion (ANTICIPATED): February 1, 2024
• Study Completion (ANTICIPATED): March 1, 2024

Study Registration Dates

• First Submitted: January 27, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (ACTUAL): February 10, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Septic Shock; Tachycardia; beta-blocker; mortality during septic shock
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Shock, Septic; Shock; Tachycardia; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Landiolol
• Other Study ID Numbers: PI2020_843_0057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No