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

Septic Shock Clinical Trial

— HyperBetashock  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04748796
• Other study ID #: PI2020_843_0057
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2021
• Est. completion date: March 2024

Study information

• Verified date: February 2023
• Source: Centre Hospitalier Universitaire, Amiens
• Contact: Slama Michel, Pr
• Phone: 03 22 08 78 41
• Email: slama.michel[@]chu-amiens.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: March 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Beta-blocker
• Mortality During Septic Shock
• Septic Shock
• Shock
• Shock, Septic
• Tachycardia

Intervention

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

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.

Locations

Country	Name	City	State
France	CHU Amiens	Amiens

Sponsors (28)

Lead Sponsor

Collaborator

Centre Hospitalier Universitaire, Amiens

Centre Hospitalier Arras, Centre Hospitalier de Beauvais, Centre Hospitalier de Bethune, Centre Hospitalier de Lens, Centre Hospitalier de Roubaix, Centre Hospitalier Universitaire de Nimes, Centre Hospitalier VALENCIENNES, CH Calais, CH Cherbourg, CH Compiègne, CH Dieppe, CH Douai, CH Elbeuf, CH Laon, CH Le Havre, CH Lomme, CH Montreuil, Groupe Hospitalier Pitié-Salpêtrière, Henri Mondor University Hospital, Hôpital Edouard Herriot, Hospital Ambroise Paré Paris, Hospital Avicenne, Tourcoing Hospital, University Hospital, Brest, University Hospital, Caen, University Hospital, Lille, University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Variation of mortality rate in landiolol group compared to control group		day 28