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

NCT05001854 | Suspended Phase 2

• 2 other identifiers: 35RC19_88602020-001430-35
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Septic Shock

Outcome Measures

Primary Outcomes (1)

• Mean arterial blood pressure (mmHg)

  Mean arterial blood pressure (mmHg) after a dose escalation of norepinephrine in increments of 0.2 μg/kg/min to a maximum dose of 1.5 μg/kg/min.

  1,5 hours after the second administration of fludrocortisone or placebo (7,5 hours)

Secondary Outcomes (49)

• Heart rate

  Baseline, before the first administration of the drug (fludrocortisone/placebo)

• Heart rate

  1,5 hours after the second administration of fludrocortisone or placebo (7,5 hours)

• Heart rate

  After the 3rd administration of fludrocortisone or placebo (12 hours)

• Heart rate

  After the 4th administration of fludrocortisone or placebo (18 hours)

• arterial pressure

  Baseline, before the first administration of the experimental drug (fludrocortisone/placebo)

Other Outcomes (1)

• Dose-response relationship

  1,5 hours after the second administration of fludrocortisone or placebo (7,5 hours)

Study Arms (2)

Fludrocortisone

EXPERIMENTAL

100 μg every 6 hours of fludrocortisone per os A pharmacokinetic study is performed in this arm

Drug: Fludrocortisone

Control

PLACEBO COMPARATOR

100 μg every 6 hours of placebo per os

Drug: Placebo

Interventions

Fludrocortisone DRUG

100 μg every 6 hours of fludrocortisone per os

Also known as: Flucortac

Fludrocortisone

Placebo DRUG

100 μg every 6 hours of placebo per os

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Patient with septic shock for less than 48 hours, defined 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,
• Hemodynamic stability for \>30 min with mean arterial pressure ≥ 65 mmHg and noradrenaline dose ≤ 0.5 μg/kg/min,
• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rennes University Hospital: lead
• H.A.C. PHARMA: collaborator

Study Sites (1)

Rennes University Hospital - Intensive Care unit

Rennes, Brittany Region, 35033, France

Location

MeSH Terms

Conditions

Shock, Septic

Interventions

Fludrocortisone

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Hydrocortisone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Bruno Laviolle, MD, PhD

  Rennes University Hospital

  STUDY CHAIR

• Harmonie Perrichet, MD

  Rennes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: August 12, 2021
• Study Start: March 31, 2022
• Primary Completion: June 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)