Septic ShockPhase 3FLUDRO-SHOCKNCT07898462
A Trial of Adjunctive Fludrocortisone (50mcg, 100mcg or Placebo) in Critically Ill Patients With Septic Shock Receiving Hydrocortisone, Evaluating Survival and Functional Recovery and the Influence of Transcriptomic Response
A Phase 3 study testing Fludrocortisone 50 mcg daily and Fludrocortisone 100 mcg daily in people with Septic Shock, run by The George Institute at 8 sites in Australia.
Trial summary
The FLUDRO-SHOCK trial is a large international randomised controlled double-blinded study aiming to improve treatment for people with septic shock, a life-threatening condition caused by severe infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Fludrocortisone 50 mcg daily and Fludrocortisone 100 mcg daily
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,200 participants
- Where
- 8 sitesAustralia
- Study dates
- 16 Oct 2026to 1 Mar 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Shock presumed due to infection
- Treatment with vasopressors to maintain a Systolic Blood Pressure (SBP) >90mmHg or Mean Arterial Pressure (MAP) > 65mmHg, after having received adequate fluid resuscitation (in the opinion of the treating clinician)
- Plasma lactate concentration >2mmol/L
- Being treated with hydrocortisone 200mg/day as adjunctive treatment for septic shock
- Being treated with one of the following:
- Invasive Mechanical Ventilation OR
Show all 9Show fewer
- Non-invasive ventilation (CPAP or BiPAP) OR
- Oxygen supplementation with an oxygen flow of >10L/min independent of delivery system and an FiO2 of 0.5 or above., OR
- Use of Veno-venous ECMO
Who cannot join
- Met all inclusion criteria for more than 12 hours
- Death is deemed imminent or inevitable by treating ICU specialist
- Patients with documented systemic fungal infection at the time of randomisation
- Patients with documented allergy to fludrocortisone
- Patients unable to receive enteral medications
- An underlying disease process with a life expectancy of less than 28 days
Show all 10Show fewer
- Pregnancy (confirmed or suspected)
- Receiving hydrocortisone (HC) or fludrocortisone (FC) for conditions other than septic shock
- Prior enrolment in this trial
- Known or documented objections to research participation
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Australia8 sites, 8 recruiting
- Not yet recruiting
The Queen Elizabeth Hospital
Adelaide, South Australia
Sandra Peake, Prof, +61 71014222, sandra.peake@sa.gov.au
Sandra Peake
- Not yet recruiting
Royal Brisbane and Women's hospital
Brisbane, Queensland, 4006
ICU Research Manager, +61 7 3646 8894, Elissa.Milford@health.qld.gov.au
Elissa Milford
- Recruiting
Princess Alexandra Hospital
Brisbane, Queensland, 4102
ICU Research Manager, +61 7 3176 7007, pah-icu-researchcoord@health.qld.gov.au
- Not yet recruiting
Caboolture Hospital
Caboolture, Queensland, 4510
ICU Research Manager, +61 75433 8888, Prashanti.Marella@health.qld.gov.au
Prashanti Marella
- Not yet recruiting
Gold Coast University Hospital
Gold Coast, Queensland, 4215
Research Manager, +61 7 5687 0000, kerina.denny@health.qld.gov.au
Kerina Denny
- Recruiting
Austin Hospital
Melbourne, Victoria
ICU Research Manager, +61 3 9496 4835, icuresearch@austin.org.au
- Not yet recruiting
Nepean Hospital
Penrith, New South Wales, 2751
ICU Research Manager, +61 24734 1388, ian.seppelt@sydney.edu.au
Ian Seppelt
- Not yet recruiting
Royal North Shore Hospital
Sydney, New South Wales, 2065
Site Principal Investigator, +61 2 94632771, Lachlan.Donaldson@health.nsw.gov.au
About this study
Official title: Adjunctive FLUDrocortisone With tRanscriptOme Evaluation in Septic SHOCK (FLUDRO-SHOCK)
The FLUDRO-SHOCK trial is a large international randomised controlled double-blinded study aiming 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. The trial will involve up to 2,200 critically ill adults in intensive care units across Australia and other countries. Researchers will track survival, organ recovery, and quality of life for up to a year. 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.
- Conditions
- Septic Shock
- Being tested
- Fludrocortisone 50 mcg daily, Fludrocortisone 100 mcg daily, Placebo
- Keywords
- Septic shock, Fludrocortisone, Sepsis, Corticosteroids
- Medical subject headings
- Shock, Septic, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fludrocortisone 50 mcg dailyDrug
The intervention will be fludrocortisone acetate 50 mcg daily, administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner.
Fludrocortisone 100 mcg dailyDrug
The intervention will be fludrocortisone acetate 100 mcg daily, administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner.
PlaceboDrug
The intervention will be placebo tablet administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner.
| Study group | Role | What they receive |
|---|---|---|
| Fludrocortisone 50 mcg daily | Active comparator | The intervention will be fludrocortisone acetate 50 mcg daily, administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner. Receives: Drug: Fludrocortisone 50 mcg daily |
| Fludrocortisone 100 mcg daily | Active comparator | The intervention will be fludrocortisone acetate 100 mcg daily, administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner. Receives: Drug: Fludrocortisone 100 mcg daily |
| Placebo | Placebo comparator | Matching placebo tablet dosed daily, administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days alive and free of organ support to day 28
Number of days during the first 28 days after randomisation on which the participant is alive and receives none of the protocol-defined forms of organ support. Organ support is defined as treatment with a vasopressor or inotropic infusion, the need for respiratory support or the need for new renal replacement therapy.
Measured: From randomisation through day 28 after randomisation.
Secondary outcomes (11)
All-cause mortality
Percentage of participants who have died from any cause by each specified follow-up time point. Mortality will be assessed separately at 28 days, 90 days, 6 months and 12 months after randomisation.
Measured: 28 days, 90 days, 6 months and 12 months after randomisation
Days alive and free of organ support to day 90
Number of days during the first 90 days after randomisation on which the participant is alive and receives none of the protocol-defined forms of organ support. Organ support is defined as treatment with a vasopressor or inotropic infusion, the need for respiratory support or the need for new renal replacement therapy.
Measured: From randomisation through day 90 after randomisation.
Proportion of patients treated with new-onset renal replacement therapy
Percentage of participants who commence renal replacement therapy after randomisation and on or before day 90.
Measured: From randomisation through day 90 after randomisation.
Days alive and free of invasive mechanical ventilation through day 90
Number of days during the first 90 days after randomisation on which the participant is alive and does not receive invasive mechanical ventilation
Measured: From randomisation through day 90 after randomisation
Days alive and outside the intensive care unit through day 90
Number of days during the first 90 days after randomisation on which the participant is alive and is not admitted to an intensive care unit
Measured: From randomisation through day 90 after randomisation
Days alive outside hospital through day 90
Number of days during the first 90 days after randomisation on which the participant is alive and is not admitted to hospital.
Measured: From randomisation through day 90 after randomisation
Number of hospital readmissions through day 90
Number of hospital readmissions per participant following discharge from the index hospital admission and occurring on or before day 90 after randomisation.
Measured: 90 days after randomisation
Number of new-onset infections during the index hospital admission
Number of new-onset infections per participant during the index hospital admission, defined by commencement of new antibiotic treatment at least 2 days after randomisation. Antibiotics commenced for perioperative prophylaxis are excluded. Includes new-onset bacteraemia.
Measured: From 2 days after randomisation until discharge from the index hospital admission.
Functional status assessed using the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)
Functional status will be assessed using the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Each item is scored from 0 (no difficulty) to 4 (extreme difficulty or inability to perform the activity), giving a total score ranging from 0 to 48. Higher scores indicate greater disability and worse functional status.
Measured: 90 days, 6 months and 12 months after randomisation.
Health-related quality of life assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) index score
EuroQol (Quality of life) 5-Dimension 5-Level (EQ-5D-5L) questionnaire. Health-related quality of life will be assessed using the country-appropriate EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. '5-D' Refers to the five dimensions of health it measures: Mobility, Usual activities, Self-care, Pain/discomfort, Anxiety/depression. '5-L' refers to the five response levels for each dimension, which are: no problems, slight, moderate, severe, extreme/unable to. Responses will be converted into an index score using the applicable country-specific value set. Higher scores indicate better health-related quality of life.
Measured: 90 days, 6 months and 12 months after randomisation.
Health-related quality of life assessed using the EuroQol Visual Analogue Scale (EQ-VAS) index score
Measuring the participant's self-rated overall health on a 0-100 scale, with 100 being the best and 0 the worst.
Measured: 90 days, 6 months and 12 months after randomisation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2026
- Study start16 Oct 2026 (estimated)
- Primary completion31 Mar 2030 (estimated)
- Study completion1 Mar 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The George Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Professor Balasubramanian (Bala) Venkatesh, Principal investigator, The George Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07898462
- Sponsor's protocol ID
- TGI 358376-74625
- Other IDs
- ACTRN12626000627358
- Acronym
- FLUDRO-SHOCK
- Status last verified
- Oct 2026
- First submitted
- 14 Jul 2026
- Last updated
- 30 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive FLUDrocortisone With tRanscriptOme Evaluation in Septic SHOCK (FLUDRO-SHOCK)
- ClinicalTrials.gov ID
- NCT07898462
- Acronym / sponsor ID
- FLUDRO-SHOCK / TGI 358376-74625
- Conditions
- Septic Shock
- Keywords
- Septic shock, Fludrocortisone, Sepsis, Corticosteroids
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,200 participants (estimated)
- Lead sponsor
- The George InstituteUniversity, hospital or other
- Study start
- 16 Oct 2026 (estimated)
- Primary completion
- 31 Mar 2030 (estimated)
- Study completion
- 1 Mar 2031 (estimated)
- First posted
- 27 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The FLUDRO-SHOCK trial is a large international randomised controlled double-blinded study aiming 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. The trial will involve up to 2,200 critically ill adults in intensive care units across Australia and other countries. Researchers will track survival, organ recovery, and quality of life for up to a year. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fludrocortisone 50 mcg daily | Active comparator | Drug: Fludrocortisone 50 mcg dailyThe intervention will be fludrocortisone acetate 50 mcg daily, administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner. |
| Fludrocortisone 100 mcg daily | Active comparator | Drug: Fludrocortisone 100 mcg dailyThe intervention will be fludrocortisone acetate 100 mcg daily, administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner. |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo tablet dosed daily, administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Shock presumed due to infection
- Treatment with vasopressors to maintain a Systolic Blood Pressure (SBP) >90mmHg or Mean Arterial Pressure (MAP) > 65mmHg, after having received adequate fluid resuscitation (in the opinion of the treating clinician)
- Plasma lactate concentration >2mmol/L
- Being treated with hydrocortisone 200mg/day as adjunctive treatment for septic shock
- Being treated with one of the following:
Key exclusion criteria (10 listed)
- Met all inclusion criteria for more than 12 hours
- Death is deemed imminent or inevitable by treating ICU specialist
- Patients with documented systemic fungal infection at the time of randomisation
- Patients with documented allergy to fludrocortisone
- Patients unable to receive enteral medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fludrocortisone 50 mcg dailyThe intervention will be fludrocortisone acetate 50 mcg daily, administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner. | Drug | Fludrocortisone 50 mcg daily |
| Fludrocortisone 100 mcg dailyThe intervention will be fludrocortisone acetate 100 mcg daily, administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner. | Drug | Fludrocortisone 100 mcg daily |
| PlaceboThe intervention will be placebo tablet administered orally or via an in situ gastric tube for 7 days or until discharge from ICU, whichever is sooner. | Drug | Placebo |
Primary outcome
Days alive and free of organ support to day 28
Time frame: From randomisation through day 28 after randomisation.
Number of days during the first 28 days after randomisation on which the participant is alive and receives none of the protocol-defined forms of organ support. Organ support is defined as treatment with a vasopressor or inotropic infusion, the need for respiratory support or the need for new renal replacement therapy.
11 secondary outcomes
All-cause mortality
Time frame: 28 days, 90 days, 6 months and 12 months after randomisation
Days alive and free of organ support to day 90
Time frame: From randomisation through day 90 after randomisation.
Proportion of patients treated with new-onset renal replacement therapy
Time frame: From randomisation through day 90 after randomisation.
Days alive and free of invasive mechanical ventilation through day 90
Time frame: From randomisation through day 90 after randomisation
Days alive and outside the intensive care unit through day 90
Time frame: From randomisation through day 90 after randomisation
Days alive outside hospital through day 90
Time frame: From randomisation through day 90 after randomisation
Number of hospital readmissions through day 90
Time frame: 90 days after randomisation
Number of new-onset infections during the index hospital admission
Time frame: From 2 days after randomisation until discharge from the index hospital admission.
Functional status assessed using the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)
Time frame: 90 days, 6 months and 12 months after randomisation.
Health-related quality of life assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) index score
Time frame: 90 days, 6 months and 12 months after randomisation.
Health-related quality of life assessed using the EuroQol Visual Analogue Scale (EQ-VAS) index score
Time frame: 90 days, 6 months and 12 months after randomisation.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Septic Shock
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
Acute Respiratory Failure, Critical Illness
Not yet recruitingObservational study
Longitudinal Trajectories of Myocardial Work in Patients With Sepsis
Sepsis, Septic Shock Hyperdynamic
RecruitingObservational study
Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Professor Balasubramanian (Bala) Venkatesh principal investigator
The George Institute
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fludrocortisone 50 mcg daily and Fludrocortisone 100 mcg daily in people with Septic Shock, run by The George Institute at 8 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Senior Project Manager (+61 2 8052 4460, fludroshock@georgeinstitute.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days alive and free of organ support to day 28 (time frame: From randomisation through day 28 after randomisation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.