E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
septic shock with hypercontractlity |
choc septique et hyperkinétique |
|
E.1.1.1 | Medical condition in easily understood language |
septic shock with hypercontractlity |
choc septique et battement du cœur très rapide |
|
E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
to demonstrate that the reduction of heart rate using the landiolol may improve the mortality of septic shock patients with tachycardia and hypercontractility in comparison to control group at day 28 |
Démontrer que le landiolol dans l'état de choc hyperkinétique en ralentissant la fréquence cardiaque peut diminuer la mortalité à 28 jours |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives are to demonstrate that the reduction of heart rate using the landiolol in comparison to standard of care may: - Reduce tachycardia - Reduce hypercontractility - Reduce shock duration - Reduce the length of stay - Reduce the multi organ failure - Reduce the incidence of atrial fibrillation |
Les objectifs secondaires sont de démontrer que la réduction de la fréquence cardiaque en utilisant le landiolol par rapport à une prise en charge standard sans ce traitement peut : - Réduire la fréquence cardiaque - Réduire l'hyperkinésie - Réduire la durée du choc - Réduire la durée d'hospitalisation - Réduire les atteintes viscérales - Réduire l'incidence de l'arythmie par fibrillation auriculaire (TAC/FA) |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The aim of this study will be to analyse hemodynamic of included patients using echocardiography. The objective is to assess the effect of landiolol compared to standard of care on cardiac function. Full echocardiography will be performed at baseline and during the follow-up at H1, H3, H6 and H12. |
Le but de cette étude sera d'analyser l'hémodynamique des patients inclus en utilisant l'échocardiographie. L'objectif est d'évaluer l'effet du landiolol par rapport à une prise en charge standard sur la fonction cardiaque. Une échocardiographie complète sera réalisée à la baseline et pendant le suivi à H1, H3, H6 et H12. |
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E.3 | Principal 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 > or = 65mmHg for more than 1 hour - Patient receiving invasive mechanical ventilation
|
- Patient de plus de 18 ans - Admis pour choc septique - Ayant reçu 30 ml/kg de remplissage vasculaire - Avec fraction d'éjection > 65% - Tachycardie > 100/ mn avec pression artérielle moyenne supérieure ou égale à 65 mmHg depuis plus d'une heure - Patient intubé ventilé bien adapté à son respirateur, sédaté analgésié |
|
E.4 | Principal 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 - Hypersensitivity to the active substance or to any of the excipients |
- Patient déjà sous béta bloquants - TAC/FA ou TV - Présence d'un pace maker - Bloc auriculo ventriculaire - HTAP connue - ScVO2<70% - Phéochromocytome non traité - Asthme sévère décompensé - Hypersensibilité à la substance active ou à l'un des excipients |
|
E.5 End points |
E.5.1 | Primary end point(s) |
mortality at day 28 |
mortalité à 28 jours |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Number of patients that achieved a reduction of heart rate equal or higher to 20% of the initial HR with landiolol - Number of days receiving catecholamines - Number of days receiving mechanical ventilation - Length of stay in ICU and hospital - SOFA score at inclusion and day 1, 2, 3, 7, 14 and 28 following the inclusion - Number of patients developing atrial fibrillation of flutter during the first three days - Hospital mortality - Safety: number of episodes of bradycardia (<50 bpm) or LVEF < 45% or MAP <65mmHg requiring an increase of Norepinephrine > 40% during the entire period of treatment with the landiolol - Unexpected cardiac arrest |
- Nombre de patients avec fréquence cardiaque réduite de plus de 20% - Nombre de jour sous ventilation mécanique - Nombre de jour sous catécholamines - Durée d'hospitalisation en réanimation et à l'hôpital - SOFA aux jours J1,2,3,7,14,28 - Nombre de patients en TAC/FA ou flutter auriculaire - Mortalité en réanimation et hospitalière - Nombre d'épisodes de bradycardie (<50 /mn) de chute tensionnelle (PAM<65 mmHg) nécessitant le recours à l'augmentation de plus de 40% de noradrénaline, fraction d'éjection<45% - Arrêt cardiaque |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
prise en charge standard |
standard of care |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 25 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 37 |
E.8.9.1 | In the Member State concerned days | |