Sepsis is a life-threatening condition caused by the body's dysregulated response to an infection. While corticosteroids are known to help stabilize blood pressure in septic shock, their ability to reduce mortality is still debated. Recent analyses suggest that combining fludrocortisone with hydrocortisone may be more effective at saving lives than hydrocortisone alone.
To test this hypothesis, a large, definitive international trial is needed. However, this research proposal is for a smaller pilot study (Phase II) involving 32 critically ill patients. The primary goal of this pilot is to determine the feasibility of conducting the subsequent large-scale trial that would compare hydrocortisone alone against the combination therapy and potentially change medical practice.
suspected or confirmed adult sepsis as defined by ≥ 2 increase in Sequential Organ Failure Assessment (SOFA) score due to infection
≥0.25 μg/kg/min of noradrenaline infusion or vasoactive-inotropic score (VIS) ≥25 to maintain mean arterial pressure (MAP) ≥65 mmHg for at least 1 hour
onset of septic shock within 24 hours
shock due to infection with no other proven or apparent cause
fludrocortisone cannot be administered within 24 hours of onset of septic shock
death is deemed imminent or inevitable by treating clinicians
limitation of therapy
an underlying disease process with a life expectancy of less than 90 days
Parallel
Fludrocortisone 100 mcg daily
DrugPatients will be given enteral fludrocortisone 100 mcg daily for 7 days or until discharge from ICU or death, whichever comes first. All patients will be treated with 7 days of intravenous hydrocortisone 50 mg every 6 hours for 7 days from randomization or until discharge from ICU or death, whichever comes first.
Placebo
DrugPatients will be given an enteral placebo tablet for 7 days or until discharge from ICU or death, whichever comes first. All patients will be treated with 7 days of intravenous hydrocortisone 50 mg every 6 hours for 7 days from randomization or until discharge from ICU or death, whichever comes first.
Number of Protocol deviations < 15%
Defined as \<15% of recruited subjects that had at least one protocol deviation during the duration of intervention
Number of Lost of concealment < 10%
Defined as \<10% of recruited subjects that lost blinding of allocations to either the patient, clinical or trial statistician
Number of Drop out < 10%
Defined as \<10% of recruited subjects who drop out of the study after recruitment
Number of Missing data < 10%
Defined as \<10% of data with missing values for each data category including lost to follow up
Number of Monthly Recruitment
Defined as the number of patients recruited per month across all study sites. In addition, screening and exclusion of subjects will be reported to inform the recruitment process and target study population of a future definitive trial.
Time to resolution of shock
Defined as time from randomization to attainment of a clinician-prescribed MAP target of \>24 hours without use of vasopressor or inotropes
28-day mortality
Defined as mortality in the first 28 days after randomization
Days alive and vasopressor-free until day 28
Defined as days alive without need for vasopressors or inotropes in the first 28 days after randomization
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