Clinical trial NCT04748796: Comparison of Landiolol Versus Standard of Care for Prevention of Mortality in Patients Hospitalized for a Septic Shock With Hypercontractility
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Septic Shock
Tachycardia
Mortality During Septic Shock
Beta-blocker
Keywords: Septic Shock
Tachycardia
mortality during septic shock
beta-blocker
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
Collaborators: name: CH Dieppe
name: CH Elbeuf
name: CH Le Havre
name: Centre Hospitalier de Beauvais
name: CH Compiègne
name: CH Laon
name: University Hospital, Caen
name: CH Cherbourg
name: University Hospital, Lille
name: CH Douai
name: CH Montreuil
name: Centre Hospitalier de Roubaix
name: Centre Hospitalier de Bethune
name: CH Lomme
name: Centre Hospitalier de Lens
name: Tourcoing Hospital
name: Centre Hospitalier VALENCIENNES
name: Centre Hospitalier Arras
name: Hospital Ambroise Paré Paris
name: University Hospital, Brest
name: Henri Mondor University Hospital
name: Hospital Avicenne
name: University Hospital, Montpellier
name: CH Calais
name: Hôpital Edouard Herriot
name: Centre Hospitalier Universitaire de Nīmes
name: Groupe Hospitalier Pitié-Salpêtrière
First posted: 2021-02-10
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 criteria: 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.

Primary outcomes:
measure: Variation of mortality rate in landiolol group compared to control group
timeFrame: day 28
Secondary outcomes:
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
Study officials:
References: