Fludrocortisone Dose Response Relationship in Septic Shock - FluDReSS

NCT04494789 | Completed Phase 2 DMC

• 1 other identifier: GI-CC35837377
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to determine the most suitable dose of Fludrocortisone in reversal of sepsis and shock associated with sepsis in patients who are admitted to the ICU. The investigators will be looking to see whether patients receiving Fludrocortisone at different doses recover quicker and spend less time in hospital and in ICU, and to understand the reasons why this happens at certain doses. Sepsis is caused by toxic substances (toxins) from bacteria and other organism entering the bloodstream from a site of infection. In some people, the infection can progress to sepsis and septic shock where the functions of organs in the body are affected. Patients suffering from sepsis and septic shock are commonly managed in the intensive care unit (ICU) where they are prescribed antibiotics as standard therapy, as well as other therapies to support the functions of the body. Fludrocortisone is a steroid that has previously shown to be beneficial to help in shock in patients in ICU, but more information is required about the exact dose that is required to achieve this. This has been shown by previous research. However, the exact role of Fludrocortisone and the best dose has not been studied adequately to date as well as the ways in how it works within the body. The study aims to look tat the dose and the way it works.

Conditions

Critically Ill; Septic Shock

Outcome Measures

Primary Outcomes (4)

• Time to resolution of shock by Intervention group allocation

  To the assess the time it takes for shock to resolve in each intervention arm

  7 DAYS

• Time to resolution of shock and Fludrocortisone Levels

  Assess the levels of fludrocortisone in the interventional groups at time of resolution of shock

  7 days

• Vasopressor Responsiveness by Intervention group allocation

  Area under the curve of vasopressor dose in each intervention arm

  7 days

• Vasopressor Responsiveness and Fludrocortisone Levels

  Area under the curve of vasopressor dose associated with fludrocortisone levels

  7 days

Secondary Outcomes (7)

• Recurrence of shock

  censored at day 28

• Ventilation free days

  censored at day 28

• ICU and hospital length of Stay

  censored at day 28

• ICU and hospital mortality

  censored at day 28

• Delta SOFA Score

  censored at day 28

Other Outcomes (3)

• Pharmacokinetic Outcome To assess the plasma levels of enterally administered fludrocortisone in all patients enrolled

  7 days

• Pharmacokinetic Outcomes - To undertake detailed analysis of fludrocortisone kinetics in a subgroup of 30 patients enrolled (10 patients in each dosing group)

  7 days

• Vascular Responsiveness Analysis

  7 days

Study Arms (4)

Fludrocortisone dosing regime: 24hrs

ACTIVE COMPARATOR

Receive 50mcg doses of fludrocortisone every 24hrs

Drug: Fludrocortisone Acetate

Fludrocortisone dosing regime: 12hrs

ACTIVE COMPARATOR

Receive 50mcg doses of fludrocortisone every 12hrs

Drug: Fludrocortisone Acetate

Fludrocortisone dosing regime: 6hrs

ACTIVE COMPARATOR

Receive 50mcg doses of fludrocortisone every 6hrs

Drug: Fludrocortisone Acetate

Control Arm

PLACEBO COMPARATOR

Receives standard treatment without fludrocortisone dosing regime

Other: Standard Therapy

Interventions

Fludrocortisone Acetate DRUG

50mcg

Fludrocortisone dosing regime: 24hrs

Standard Therapy OTHER

NO Fludrocortisone

Control Arm

Eligibility Criteria

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

You may qualify if:

• Aged 18 years or older
• Documented site, or strong suspicion of infection with 2 of the 4 clinical signs of inflammation:
• Core temperature \> 38oC or \< 35oC
• Heart rate \> 90bpm
• Respiratory rate \> 20bpm, or PaCO2 \< 32mmHg, or mechanical ventilation
• White cell count \> 12 x 109/L or \< 4 x 109/L or \> 10% immature neutrophils\\
• Being treated with Hydrocortisone at a daily dose of 200mg / day as adjunctive treatment for sepsis
• Being treated with mechanical ventilation at the time of randomisation (includes mask BiPAP/CPAP)
• Being treated with continuous vasopressors or inotropes to maintain a systolic blood pressure \> 90mmHg, or mean arterial pressure \> 60mmHg or a MAP target set by the treating clinician for maintaining perfusion
• Administration of vasopressors or inotropes for \> 4 hours and present at time of randomisation

You may not qualify if:

• Patients taking long term corticosteroids or fludrocortisone
• Patients with systemic fungal infection
• Death is deemed inevitable or imminent during this admission and either the attending physician, patient or surrogate legal decision maker is not committed to active treatment
• Patient unable to receive enteral medication
• Death from underlying disease likely within 90 days
• Patient has been previously enrolled in the study

Sponsors & Collaborators

• The George Institute: lead

Study Sites (9)

Blacktown Hospital

Sydney, New South Wales, Australia

Location

Royal North Shore Hospital

Sydney, New South Wales, Australia

Location

Royal Brisbane Women's Hospital

Brisbane, Queensland, Australia

Location

Wesley Hospital

Brisbane, Queensland, Australia

Location

Gold Coast University Hospital

Gold Coast, Queensland, Australia

Location

Mater Misericordiae

Raymond Terrace, Queensland, 4101, Australia

Location

Princess Alexandra Hospiital

Woolloongabba, Queensland, 4102, Australia

Location

Queen Elizabeth II Hospital

Adelaide, South Australia, Australia

Location

Austin Hospital

Melbourne, Victoria, Australia

Location

MeSH Terms

Conditions

Critical Illness; Shock, Septic

Interventions

fludrocortisone acetate; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• James Walsham, MB ChB, MRCP, FCICM.

  Princess Alexandra Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2020
• First Posted: July 31, 2020
• Study Start: February 11, 2021
• Primary Completion: April 30, 2023
• Study Completion: June 30, 2023
• Last Updated: January 18, 2024

Record last verified: 2024-01

Locations

AU (9)