Adjunctive Fludrocortisone in Septic Shock (AFLUDROS-1)

The Chinese University of Hong Kong

Status and phase: Enrolling; Phase 2

Conditions: Sepsis at Intensive Care Unit; Sepsis and Septic Shock; Sepsis - to Reduce Mortality in the Intensive Care Unit; Septic Shock; Sepsis

Treatments: Drug: Fludrocortisone 100 mcg daily; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07451886

2024.398

Details and patient eligibility

About

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.

Full description

Design: Pilot, multicenter, randomized, double-blind, placebo-controlled trial on use of adjunctive fludrocortisone in critically ill patients with septic shock.

Objective: Determine feasibility of conducting a large, international, multicenter, double-blind, randomized, placebo controlled efficacy trial of adjunctive fludrocortisone to improve septic shock mortality.

Setting: 6 intensive care units (ICU) in Hong Kong, Australia and Singapore. Participants: 32 adult participants with suspected or confirmed septic shock within 24 hours of onset of shock and mechanical ventilation. Exclusion criteria are pregnancy, limitation of therapy, prescribed fludrocortisone for other medical condition, fludrocortisone cannot be administered within 24 hours of shock onset.

Interventions: Enteral 100 mcg fludrocortisone daily or placebo for up to 7 days or until death or discharge from ICU, whichever comes first.

Main outcome measures: Primary outcome is fulfillment of all pre-specified endpoints of feasibility criteria: protocol deviation <15%, lost of concealment <10%, drop out rate <10% and missing data <10%. Secondary outcomes include monthly recruitment rate, time to resolution of shock, 28-day mortality, days alive and free from organ support, severe electrolyte abnormality.

Data analysis: Each feasibility criterion will be assessed amongst all study participants. Intention to treat analysis will be used to calculate differences in secondary outcomes between treatment groups.

Expected results: Feasibility criteria will be met and demonstrate potential to scale-up to a large, international, multicenter, double-blind, randomized, placebo-controlled trial of adjunctive fludrocortisone to improve septic shock mortality.

Enrollment: 32 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. suspected or confirmed adult sepsis as defined by ≥ 2 increase in Sequential Organ Failure Assessment (SOFA) score due to infection
2. ≥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
3. onset of septic shock within 24 hours
4. shock due to infection with no other proven or apparent cause
5. hypoperfusion defined as arterial or venous lactate concentration >2.0 mmol/L
6. mechanical ventilation

Exclusion criteria

1. fludrocortisone cannot be administered within 24 hours of onset of septic shock
2. death is deemed imminent or inevitable by treating clinicians
3. limitation of therapy
4. an underlying disease process with a life expectancy of less than 90 days
5. pregnancy (confirmed or suspected)
6. receiving immunomodulatory agents including hydrocortisone > 300mg/day
7. enteral medication cannot be administered
8. prescribed fludrocortisone for other medical condition
9. contraindication to hydrocortisone or fludrocortisone

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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32 participants in 2 patient groups, including a placebo group

Fludrocortisone

Experimental group

Treatment:

Drug: Fludrocortisone 100 mcg daily

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo