Ignite Creation Date:
2024-05-06 @ 3:01 PM
Last Modification Date:
2024-10-26 @ 1:41 PM
Study NCT ID:
NCT04494789
Status:
COMPLETED
Last Update Posted:
2024-01-18
First Post:
2020-07-19
Brief Title:
Fludrocortisone Dose Response Relationship in Septic Shock - FluDReSS
Sponsor:
The George Institute
Organization:
The George Institute
Study Overview
Official 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
Status:
COMPLETED
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FluDReSS
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
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
Detailed Description:
Aim
1 To conduct a multi-centre randomised controlled trial to assess the effect of 3 different dose regimens of fludrocortisone on shock reversal in septic shock patients treated with hydrocortisone
2 To assess the temporal changes in endocrine inflammatory and gene expression markers in septic shock patients
Hypotheses
In patients with septic shock treated with hydrocortisone
1 The addition of fludrocortisone to hydrocortisone results in improved vascular responsiveness to vasopressors as compared to hydrocortisone alone
2 The improvement of vascular responsiveness with fludrocortisone is in a dose dependent manner
3 Enterally administered fludrocortisone results in adequate plasma level
4 Patients who have early reversal of shock have higher concentrations of angiotensin II and angiotensin II-receptor expression and reduced angiotensin converting enzyme 2 ACE 2 concentrations at baseline and throughout the course of their illness
5 Patients who have early reversal of shock have higher concentrations of plasma free cortisol aldosterone and glucocorticoid and mineralocorticoid receptor expression at baseline and throughout the course of their illness
6 Patients who demonstrate evidence of both greater angiotensin II and glucocorticoid receptor expression will have earlier shock reversal than those who have an increase in expression of either of these receptors
7 There is a different temporal change in the plasma concentrations and receptor expression profiles in early shock reversal patients vs delayed shock reversal patients
300 patients will be recruited and randomised to enteral doses of 50mcg fludrocortisone Q24H Q12H Q6H or to the control arm of the study The study will enrol patients admitted to a participating intensive care unit and who meet all the inclusion criteria and no exclusion criteria Patients in a fludrocortisone arm will receive enteral fludrocortisone for a maximum of 7 days or until sustained shock reversal or until discharge from ICU whichever is earlier
Blood samples acquired will be analysed for
Endocrine - Cortisol free cortisol aldosterone and metabolites
Inflammatory - Cytokine profiles markers of vasoplegia
Gene Expression - Whole genome RNA sequencing and single cell sequencing
To assess the plasma levels following enteral administration of fludrocortisone in all patients enrolled to undertake detailed analysis of fludrocortisone kinetics in a subgroup of 30 patients enrolled 10 patients in each dosing group
For all patients data will be collected at baseline and daily whilst in the ICU for up to 8 days Patients will be followed up to time of discharge from hospital or day 28 if they are still in hospital whichever occurs first
1 To conduct a multi-centre randomised controlled trial to assess the effect of 3 different dose regimens of fludrocortisone on shock reversal in septic shock patients treated with hydrocortisone
2 To assess the temporal changes in endocrine inflammatory and gene expression markers in septic shock patients
Hypotheses
In patients with septic shock treated with hydrocortisone
1 The addition of fludrocortisone to hydrocortisone results in improved vascular responsiveness to vasopressors as compared to hydrocortisone alone
2 The improvement of vascular responsiveness with fludrocortisone is in a dose dependent manner
3 Enterally administered fludrocortisone results in adequate plasma level
4 Patients who have early reversal of shock have higher concentrations of angiotensin II and angiotensin II-receptor expression and reduced angiotensin converting enzyme 2 ACE 2 concentrations at baseline and throughout the course of their illness
5 Patients who have early reversal of shock have higher concentrations of plasma free cortisol aldosterone and glucocorticoid and mineralocorticoid receptor expression at baseline and throughout the course of their illness
6 Patients who demonstrate evidence of both greater angiotensin II and glucocorticoid receptor expression will have earlier shock reversal than those who have an increase in expression of either of these receptors
7 There is a different temporal change in the plasma concentrations and receptor expression profiles in early shock reversal patients vs delayed shock reversal patients
300 patients will be recruited and randomised to enteral doses of 50mcg fludrocortisone Q24H Q12H Q6H or to the control arm of the study The study will enrol patients admitted to a participating intensive care unit and who meet all the inclusion criteria and no exclusion criteria Patients in a fludrocortisone arm will receive enteral fludrocortisone for a maximum of 7 days or until sustained shock reversal or until discharge from ICU whichever is earlier
Blood samples acquired will be analysed for
Endocrine - Cortisol free cortisol aldosterone and metabolites
Inflammatory - Cytokine profiles markers of vasoplegia
Gene Expression - Whole genome RNA sequencing and single cell sequencing
To assess the plasma levels following enteral administration of fludrocortisone in all patients enrolled to undertake detailed analysis of fludrocortisone kinetics in a subgroup of 30 patients enrolled 10 patients in each dosing group
For all patients data will be collected at baseline and daily whilst in the ICU for up to 8 days Patients will be followed up to time of discharge from hospital or day 28 if they are still in hospital whichever occurs first
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None