There is one clinical trial.
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.
300 patients will be recruited and randomised to enteral doses of 50mcg fludrocortisone Q24H, Q12H, Q6H or to the control arm of the study. --- Q24H ---
Description: To the assess the time it takes for shock to resolve in each intervention arm
Measure: Time to resolution of shock by Intervention group allocation Time: 7 DAYSDescription: Assess the levels of fludrocortisone in the interventional groups at time of resolution of shock
Measure: Time to resolution of shock and Fludrocortisone Levels Time: 7 daysDescription: Area under the curve of vasopressor dose in each intervention arm
Measure: Vasopressor Responsiveness by Intervention group allocation Time: 7 daysDescription: Area under the curve of vasopressor dose associated with fludrocortisone levels
Measure: Vasopressor Responsiveness and Fludrocortisone Levels Time: 7 daysDescription: Time between a new episode of shock after reversal of the initial episode
Measure: Recurrence of shock Time: censored at day 28Description: Number of Days that are without ventilation during admission
Measure: Ventilation free days Time: censored at day 28Description: Total number of days in ICU and in hospital for the index admission
Measure: ICU and hospital length of Stay Time: censored at day 28Description: 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
Measure: ICU and hospital mortality Time: censored at day 28Description: Baseline SOFA score to SOFAmax - numerical calculation based on scoring system of each participant during their admission
Measure: Delta SOFA Score Time: censored at day 28Description: Maximum SOFA score for each participant during their admission
Measure: Maximal SOFA score Time: censored at day 28Description: This is the number of new infections that occur >48hrs after commencing study drug
Measure: Superinfection Time: censored at day 28Description: Time to peak concentration of Fludrocortisone
Measure: Pharmacokinetic Outcome To assess the plasma levels of enterally administered fludrocortisone in all patients enrolled Time: 7 daysDescription: Time to absorption, clearance and metabolism of fludrocortisone in participants in each intervention arm except for the control arm
Measure: Pharmacokinetic Outcomes - To undertake detailed analysis of fludrocortisone kinetics in a subgroup of 30 patients enrolled (10 patients in each dosing group) Time: 7 daysDescription: Acquisition of blood samples at 4 timepoints over the first 7 days or until discharge from ICU for exploratory analysis to assess a range of biomarkers and their interactions with the primary outcomes
Measure: Vascular Responsiveness Analysis Time: 7 days