Hemodynamics Effects of Fludrocortisone on the Pressor Response to Noradrenaline Septic Shock Patients

• Status: Not yet recruiting
• Trial end date: 2024-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The benefit of low-dose steroids in septic shock is still debated today, especially with mineralocorticoids. Fludrocortisone is a synthetic mineralocorticoid, an analogue of aldosterone, which has shown, in combination with hydrocortisone, a favorable effect on the mortality of septic shock patients with relative adrenal insufficiency. In a previous study in healthy volunteers, we showed for the first time that fludrocortisone at a dose of 400 μg per day significantly improved the pressor response to phenylephrine. These results confirm the observations reported in rats with endotoxin shock, where fludrocortisone was shown to significantly increase blood pressure and contractile response to phenylephrine. These encouraging results argue for a potential vascular beneficial effect of fludrocortisone and need to be confirmed in a population of septic shock patients. In this context, we aimed to evaluate the effect of oral administration of 100 μg every 6 hours of fludrocortisone on vascular responsiveness to noradrenaline in septic shock patients.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rennes University Hospital
• Collaborator: H.A.C. PHARMA
• Treatments: Fludrocortisone

Criteria

Inclusion Criteria:

• Age > 18 years

• Patient with septic shock for less than 24 hours, defined according to The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) by the combination of:

• Sepsis defined as organ dysfunction caused by an inappropriate host response to infection (increase in SOFA score of at least 2 points secondary to infection),

• Persistent hypotension requiring vasopressor drugs to maintain mean arterial pressure ≥ 65 mmHg,

• Serum lactate level > 2 mmol/l despite adequate vascular filling.

• Hemodynamic stability for >30 min with mean arterial pressure ≥ 65 mmHg and noradrenaline dose ≤ 0.5 μg/kg/min,

• Consent signed by the patient, family member, or legal representative or inclusion under emergency procedure,

• Negative to a diagnostic test for SARS-CoV2 less than 72 hours old; the test used must be on the the list published on the Ministry of Solidarity and Health website

Non-inclusion Criteria:

• Current treatment with steroids or other treatment that may affect the hypothalamic-pituitary-adrenal axis,

• Anesthetic induction with etomidate within 6 hours prior to randomization given its selective inhibitory effect on 11 β-hydroxylase,

• Known hypersensitivity to fludrocortisone (or any of its excipients), or to tetracosactide (Synacthen®),

• Disturbed gastric emptying (gastric residue > 500 ml) in the absence of an alternative route of administration available (naso-jejunal tube or jejunostomy),

• Pregnant or nursing woman,

• Patient participating in another trial, possibly interfering with the study procedures,

• Person not affiliated to a social security system,

• Known situation of deprivation of freedom (safeguard of justice), guardianship or curatorship,

• Patient with a life expectancy of less than 24 hours.

• Patient with known or suspected SARS-CoV2 pneumonia

Exclusion criteria:

• Patients under court 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 end point.

• Catecholamine withdrawal before evaluation of the primary end point.