septic shock
Conditions
Interventions
Trade Name: FLUCORTAC 50 microgrammes, comprimé sécable
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
CHU Rennes
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Adult 18 years of age or older - Patient presenting with septic shock for less than 24 hours, as defined by The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) by the association of: Sepsis defined as an organ dysfunction caused by an inappropriate host response to infection (increase in SOFA score of at least 2 points following infection), Persistent hypotension requiring vasopressor drugs to maintain MAP = 65 mmHg, Serum lactate level > 2 mmol/l despite adequate vascular filling. - Hemodynamic stability for more than 30 min with mean blood pressure = 65 mmHg and noradrenaline dose = 0.5 µg/kg/min, - Consent signed by the patient, relative or legal representative or inclusion under emergency procedure. 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Non-inclusion criteria: - Ongoing treatment with steroids or other treatment that may act on the hypothalamic-pituitary-adrenal axis, - Anaesthetic induction with etomidate in the 6 hours prior to randomization due to its selective inhibitory effect on 11 ß-hydroxylase, - Known hypersensitivity to fludrocortisone (or one of its excipients), or tetracosactide (Synacthène®), - Disorders of gastric emptying (gastric residue > 800 ml), - Pregnant or breastfeeding woman, - Concomitant participation in another trial that may interfere with study procedures, - A person who is not affiliated to social security , - Known situation of deprivation of liberty (safeguarding of justice), guardianship or curatorship, - Patient whose life expectancy is less than 24 hours. Exclusion criteria: - Patients under legal protection will be excluded as soon as the investigator is aware of their status. - Hemodynamic worsening with noradrenaline dose > 1.5 µg/kg/min before evaluation of the primary endpoint. - Catecholamine withdrawal prior to evaluation of the primary endpoint.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the study is to evaluate the effect of oral administration of fludrocortisone (100 µg every 6 hours) on vascular reactivity to norepinephrine in patients in septic shock.;Secondary Objective: The secondary objectives are to evaluate the clinical, biological effects and pharmacokinetic profile of oral administration of fludrocortisone (100 µg every 6 hours) in patients in septic shock.;Primary end point(s): The main primary endpoint is the vascular reactivity explored by the realization of a pressure dose-response curve judged on the mean blood pressure at increasing doses of norepinephrine.;Timepoint(s) of evaluation of this end point: The primary endpoint is assessed 1.5 hours after the second administration of the treatment or its placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Hemodynamics: - Heart rate, Systolic, Diastolic and Mean Arterial Pressure measured invasively by an arterial catheter. - Cardiac Output, Cardiac Index, Indexed Systemic Vascular Resistances, Evaluation of Cardiac Preload by Indexed Global Telediastolic Volume, "Optimal" Cardiac Preload by ejection volume variability in the ventilated patient and measurement of Indxed Extra Vascular Pulmonary Water with PiCCO® monitor. Patient's follow-up: - Mortality at D28 and D90, - Length of hospitalisation in intensive care, length of hospitalisation in the care unit (excluding rehabilitation) - Weaning time for cathecolamines - Mechanical ventilation time Biological: - Adrenal function assessed at inclusion by a Synacthène® test - Markers of inflammation: IFN?, TNF a, IL1ß, IL6, IL10 - Blood and urinary kalemia and natremia Pharmacokinetics of fludrocortisone: - Area under the plasma concentration-time curve from administration of treatment (t0) to the next dose at 6h (AUC0-6); - Area under the plasma concentration-time curve from treatment administration (t0) and extrapolated to infinity (AUC0-8), according to the formula AUC0-8 = AUC0-t + Ct/k where Ct is the last measurable plasma concentration and k is the elimination constant of the product; - Half-life (t1/2) determined according to the formula t1/2 = Ln2/k ; - Apparent total clearance (ClT) and apparent volume of distribution (Vd) calculated according to the formulas ClT = F.Dose/ AUC0-8 and Vd = ClT/k where F is the absolute bioavailability. ;Timepoint(s) of evaluation of this end point: Haemodynamic data are collected: - before the 1st administration of the experimental drug (fludrocortisone or placebo) - at T2 (1.5 hours after the 2nd administration of the experimental drug) - when assessing the main judging criterion (at the levels) - at T3 (4.5 h after T2) - at T4 (6 hours after T3). Biological data will be collected: - at the inclusion - before the 1st adm | — |
Countries
France
Contacts
Public ContactClaire FOUGEROU
CHU de Rennes
Outcome results
None listed