Evaluation of the hemodynamic effects of fludrocortisone on the pressive response to norepinephrine in patients in septic shock

Phase 1

• Conditions: septic shock; Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]

• Registration Number: EUCTR2020-001430-35-FR
• Lead Sponsor: CHU Rennes

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-02-02
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

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

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.

- 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.