This is the STAGING server for testing & practice only.

Trial Summary

A harmonised trial of corticosteroids in septic shock incorporating the FludrocortIsoNE in Septic Shock Evaluation (FINESSE) trial & CoRticosteroid Evaluation in SepTic shock using transcriptomic endotyping and a precision medicine approach (CREST) trial.

Goal

FLUDRO-SHOCK is a harmonised phase 3 multi-centre, adaptive, randomised, blinded, placebo-controlled trial of adjunctive fludrocortisone in critically ill patients with septic shock receiving hydrocortisone. The trial will evaluate survival and functional recovery and explore whether a person’s unique immune response, based on their genes, affects how well the treatment works. The goal is to find the most effective and personalised way to use steroids in septic shock, potentially saving lives and improving long-term outcomes.

The primary objective is to determine in critically ill patients with septic shock who are receiving hydrocortisone:

  • if adding fludrocortisone in two different doses (50 mcg or 100 mcg) compared to placebo, improves survival and functional recovery
  • to better understand how the body responds to infection during septic shock, and whether some people are likely to benefit more from fludrocortisone than others

Rationale

The FLUDRO-SHOCK trial aims to improve treatment for people with septic shock—a life-threatening condition caused by severe infection. Patients with septic shock receive a steroid called hydrocortisone, but it is unclear whether adding another steroid, fludrocortisone, improves their chances of recovery and survival. This study will test two doses of fludrocortisone (50 mcg and 100 mcg) against a placebo to see which works best. It will also explore whether a person’s unique immune response, based on their genes, affects how well the treatment works.

To address the key knowledge gaps about steroids for septic shock, the Critical Care Program of The George Institute for Global Health submitted two research grant applications to generate conclusive evidence on:

  • the role and optimal dose of fludrocortisone in the management of septic shock, and
  • the influence of transcriptomic endotype on clinical response to fludrocortisone.

Both grants were awarded, and to ensure completion of both grants (and not competition for the same patient population), the trial management committees have harmonised the trial protocols into the FLUDRO-SHOCK trial.

Overview

  • Harmonised phase 3 multi-centre, adaptive, randomised, blinded, placebo-controlled trial
  • Up to 2,200 critically ill adults in intensive care units across Australia and other countries
  • Participants will be randomised (by computer) to one of the following groups:
    • 50 mcg of oral or enteral fludrocortisone daily, or
    • 100 mcg of oral or enteral fludrocortisone daily, or
    • Matching oral or enteral placebo
  • Participants will receive trial treatment for up to seven days while in intensive care (ICU)
  • Participants’ regular ICU and hospital treatments and care will continue as usual
  • Researchers will track survival, organ recovery, and quality of life for up to a year
  • By taking part, participants will help the researchers understand whether fludrocortisone is useful in treating septic shock. This knowledge will help improve treatment for people in the future.

Outcomes

Primary Outcome:

  • Days alive and free of organ support to 28 days after randomisation

Secondary Outcomes:

  • Mortality (28 days, 90 days, 6 months and 12 months)
  • Days alive and free of organ support and mechanical ventilation to 90 days
  • New renal replacement therapy and hospital readmissions to 90 days
  • Days alive and out of ICU/hospital to 90 days
  • Number of new onset infections during index hospital admission
  • Long term quality of life outcomes at 90 days, 6 months and 12 months (EQ-5D-5L and WHO-DAS 2.0 12 items)
  • Health economic analysis

Safety Outcomes:

  • Electrolyte abnormalities
  • Fluid balance

Funding

The CREST trial has received funding from the National Health and Medical Research Council (NHMRC) via project grant ID 2043244.

The FINESSE trial has received funding from the Medical Research Future Fund (MRFF) via project grant ID 2036019.

Endorsement/Partners

The protocol will be submitted to The Australian and New Zealand Intensive Care Society – Clinical Trials Group (ANZICS-CTG) for endorsement.

Sepsis Australia and their Consumer Partner and Advocacy Program (SACPAP).

Registration

Australian New Zealand Clinical Trials Registry: ACTRN12626000627358

Ethics Approval

This study has been approved by the Northern Sydney Local Health District Research Ethics Committee (2025/ETH02083).

Contact

For more information about this study, please contact fludroshock@georgeinstitute.org