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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04494789




Registration number
NCT04494789
Ethics application status
Date submitted
19/07/2020
Date registered
31/07/2020
Date last updated
1/04/2021

Titles & IDs
Public title
Fludrocortisone Dose Response Relationship in Septic Shock - FluDReSS
Scientific title
A Phase II Open Label Randomised Controlled Clinical Trial of Different Dosing Regimens of Fludrocortisone in Septic Shock With Assessment of Temporal Changes in Hormonal, Inflammatory, and Genetic Markers of Vascular Responsiveness
Secondary ID [1] 0 0
GI-CC35837377
Universal Trial Number (UTN)
Trial acronym
FluDReSS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Critically Ill 0 0
Septic Shock 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Fludrocortisone Acetate
Treatment: Drugs - Fludrocortisone Acetate
Treatment: Drugs - Fludrocortisone Acetate
Other interventions - Standard Therapy

Active Comparator: Fludrocortisone dosing regime: 24hrs - Receive 50mcg doses of fludrocortisone every 24hrs

Active Comparator: Fludrocortisone dosing regime: 12hrs - Receive 50mcg doses of fludrocortisone every 12hrs

Active Comparator: Fludrocortisone dosing regime: 6hrs - Receive 50mcg doses of fludrocortisone every 6hrs

Placebo Comparator: Control Arm - Receives standard treatment without fludrocortisone dosing regime


Treatment: Drugs: Fludrocortisone Acetate
50mcg

Treatment: Drugs: Fludrocortisone Acetate
100mcg

Treatment: Drugs: Fludrocortisone Acetate
200mcg

Other interventions: Standard Therapy
NO Fludrocortisone

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to resolution of shock by Intervention group allocation - To the assess the time it takes for shock to resolve in each intervention arm
Timepoint [1] 0 0
7 DAYS
Primary outcome [2] 0 0
Time to resolution of shock and Fludrocortisone Levels - Assess the levels of fludrocortisone in the interventional groups at time of resolution of shock
Timepoint [2] 0 0
7 days
Primary outcome [3] 0 0
Vasopressor Responsiveness by Intervention group allocation - Area under the curve of vasopressor dose in each intervention arm
Timepoint [3] 0 0
7 days
Primary outcome [4] 0 0
Vasopressor Responsiveness and Fludrocortisone Levels - Area under the curve of vasopressor dose associated with fludrocortisone levels
Timepoint [4] 0 0
7 days
Secondary outcome [1] 0 0
Recurrence of shock - Time between a new episode of shock after reversal of the initial episode
Timepoint [1] 0 0
censored at day 28
Secondary outcome [2] 0 0
Ventilation free days - Number of Days that are without ventilation during admission
Timepoint [2] 0 0
censored at day 28
Secondary outcome [3] 0 0
ICU and hospital length of Stay - Total number of days in ICU and in hospital for the index admission
Timepoint [3] 0 0
censored at day 28
Secondary outcome [4] 0 0
ICU and hospital mortality - The number of deaths that are recorded in participants and the location of the deaths when in hospital - ICU or ward. This will include cause of death
Timepoint [4] 0 0
censored at day 28
Secondary outcome [5] 0 0
Delta SOFA Score - Baseline SOFA score to SOFAmax - numerical calculation based on scoring system of each participant during their admission
Timepoint [5] 0 0
censored at day 28
Secondary outcome [6] 0 0
Maximal SOFA score - Maximum SOFA score for each participant during their admission
Timepoint [6] 0 0
censored at day 28
Secondary outcome [7] 0 0
Superinfection - This is the number of new infections that occur >48hrs after commencing study drug
Timepoint [7] 0 0
censored at day 28

Eligibility
Key inclusion criteria
1. Aged 18 years or older

2. Documented site, or strong suspicion of infection with 2 of the 4 clinical signs of
inflammation:

1. Core temperature > 38oC or < 35oC

2. Heart rate > 90bpm

3. Respiratory rate > 20bpm, or PaCO2 < 32mmHg, or mechanical ventilation

4. White cell count > 12 x 109/L or < 4 x 109/L or > 10% immature neutrophils\

3. Being treated with Hydrocortisone at a daily dose of 200mg / day as adjunctive
treatment for sepsis

4. Being treated with mechanical ventilation at the time of randomisation (includes mask
BiPAP/CPAP)

5. 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

6. Administration of vasopressors or inotropes for > 4 hours and present at time of
randomisation
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Met all inclusion criteria more than 24 hours ago

2. Patients taking long term corticosteroids or fludrocortisone

3. Patients with systemic fungal infection

4. 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

5. Patient unable to receive enteral medication

6. Death from underlying disease likely within 90 days

7. Patient has been previously enrolled in the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Bankstown Hospital - Sydney
Recruitment hospital [2] 0 0
Blacktown Hospital - Sydney
Recruitment hospital [3] 0 0
Royal North Shore Hospital - Sydney
Recruitment hospital [4] 0 0
Royal Brisbane Women's Hospital - Brisbane
Recruitment hospital [5] 0 0
Wesley Hospital - Brisbane
Recruitment hospital [6] 0 0
Gold Coast University Hospital - Gold Coast
Recruitment hospital [7] 0 0
Princess Alexandra Hospiital - Woolloongabba
Recruitment hospital [8] 0 0
Queen Elizabeth II Hospital - Adelaide
Recruitment hospital [9] 0 0
Austin Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Gold Coast
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
- Adelaide
Recruitment postcode(s) [6] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
The George Institute
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04494789
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James Walsham, MB ChB, MRCP, FCICM.
Address 0 0
Princess Alexandra Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Dorrilyn Rajbhandari
Address 0 0
Country 0 0
Phone 0 0
0410530548
Fax 0 0
Email 0 0
drajbhandari@georegeinstitute.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04494789