Trial subjects are adult patients with septic shock. MedDRA version: 20.0 Level: PT Classification code 10040070 Term: Septic shock System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: PROCORALAN 5 mg
Product Name: PROCORALAN 5 mg
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Assistance Publique - Hôpitaux de Paris
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -18 years of age or older; -Proven or suspected site of infection; -Septic shock (defined as hypotension unresponsive to fluid resuscitation and requiring vasopressor treatment to maintain adequate blood pressure) for at least 6 hours and less than 24 hours; -In sinus rhythm with heart rate = 95 bpm at time of randomization; -Informed consent obtained in accordance with local regulations; -Affiliation to a social security regime. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 215 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 215
Exclusion criteria
Exclusion criteria: -Age 2.4 µg/kg/min; these doses should be multiplied by two for noradrenaline salt (tartrate or bitartrate). -Co-treatment with drugs inducing bradycardia, QT lengthening or strong inhibition of CYP4503A4, pacemaker, defibrillator, kalemia <3 mM -Known pregnancy, breast feeding, women with of childbearing potential will be tested for pregnancy and excluded if pregnant -Known allergy to ivabradine or to any of the excipients, retinitis pigmentosa, congenital galactosemia, lactase deficiency, glucose or galactose malabsorption -Severe renal failure (creatinine clearance <15 ml/min) or hepatic failure (prothrombin time <20%), -Enteral feeding impossible, vomiting, congenital galactosemia, lactase deficiency, glucose-galactose malabsorption syndrome. -Tachycardia due to hyperthyroidism, pheochromocytoma or severe anemia (<7 g/dL) -Prior enrolment in the trial, participation in another interventional study on septic shock, -Known legal incapacity (patients under guardianship or curatorship), -Decision to limit full care taken before obtaining informed consent. -Patient under AME (state emergency medical help)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the efficacy of ivabradine in controlling heart rate and improving 28-day survival in patients with septic shock. These objectives will be assessed via a two-stage trial: activity (focused on heart rate control) and efficacy (focused on mortality). ;Secondary Objective: -determine the tolerance of ivabradine; -evaluate the impact of ivabradine-driven heart rate control on systemic hemodynamics, myocardial stress, organ dysfunction, morbidity, and intensive care mortality; -determine the pharmacokinetics of ivabradine. ;Primary end point(s): There are two primary endpoints: -for activity and treatment selection at interim analysis: the percentage of patients with heart rate within the predefined threshold (80-94 bpm) at hour-48; -for efficacy and the final analysis: 28-day mortality. ;Timepoint(s) of evaluation of this end point: - At hour-48 - At day-28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a) Tolerance of ivabradine: percentage of patients with bradycardia, atrial fibrillation, phosphenes or blurred vision up to day-17; b) Percentage of patients with a heart rate within the target range (80-94 bpm) at hour-72; percentage of heart rate measurements (assessed every 3 to 4 hours) within the target range at hour-72; changes in heart rate, mean arterial pressure and cardiac output evaluated by the area under the curve (AUC) versus time; c) Organ failures free days (SOFA<3 for each organ) at day-14 and day-28, number of vasopressor- and mechanical ventilation-free days at day-14 and day-28, lactate clearance at day-2 and day-3; d) Repeated echocardiographies [to assess left ventricle systolic (ejection fraction, s wave at mitral annulus by tissue Doppler, and global longitudinal strain if available), and diastolic (early and late mitral inflow by pulse and tissue Doppler) functions] and biomarker assessment (natriurectic peptide and troponin); e) Pharmacokinetics of ivabradine; f) Mortality at ICU discharge, hospital discharge, and day-90; ICU- and hospital-free days at day-28 and day-90 ;Timepoint(s) of evaluation of this end point: - day 17 - 72 hours - day 14 - day 28 - day 2 - day 3 - day 90 | — |
Countries
France
Contacts
Public Contactproject manager
Assistance Publique - Hôpitaux de Paris
Outcome results
None listed