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

GI-CC35837377

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.

2021-02-11

2023-04-30

2023-06-30

Completed

Early phase I

155

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 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

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2024-01-18