Adjunctive Fludrocortisone in Septic Shock (AFLUDROS-1)

Adjunctive Fludrocortisone in Septic Shock: a Multicenter, Double-blind, Randomized, Placebo-controlled Pilot Trial (AFLUDROS-1)

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.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock; Sepsis and Septic Shock; Sepsis at Intensive Care Unit; Sepsis - to Reduce Mortality in the Intensive Care Unit
• Intervention / Treatment: Drug: Fludrocortisone 100 mcg daily; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lowell Ling, MBBS; Phone Number: (852) 35052735; Email: lowell.ling@cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Prince of Wales Hospital
    • Contact: Ling Lowell, MBBS; Phone Number: +852 35051311; Email: lowell.ling@cuhk.edu.hk
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • Princess Margaret Hospital
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • North District Hospital
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • Pamela Youde Nethersole Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Patients 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.
Experimental: Fludrocortisone	Drug: Fludrocortisone 100 mcg daily; Patients 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Protocol deviations < 15%	Defined as <15% of recruited subjects that had at least one protocol deviation during the duration of intervention	End of study approximately 20 months
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	End of study approximately 20 months
Number of Drop out < 10%	Defined as <10% of recruited subjects who drop out of the study after recruitment	End of study approximately 20 months
Number of Missing data < 10%	Defined as <10% of data with missing values for each data category including lost to follow up	End of study approximately 20 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	End of study approximately 20 months
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	Until patient discharge from ICU
28-day mortality	Defined as mortality in the first 28 days after randomization	First 28 days after enrollment
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	First 28 days after enrollment
Days alive and ventilator-free until day 28	Defined as days alive without mechanical ventilation in the first 28 days after randomization	First 28 days after enrollment
Days alive and dialysis-free until day 28	Defined as days alive without any forms of renal replacement therapy in the first 28 days after randomization	First 28 days after enrollment
Days alive and free from organ support	Defined as days alive without need for mechanical ventilation, vasopressors or dialysis in the first 28 days after randomization	First 28 days after enrollment
Number of new onset infections	Defined as new nosocomial infection 2 days after randomization until the first 28 days after randomization	First 28 days after enrollment
Severe electrolyte abnormality	Defined as plasma sodium ≥ 155 mmol/L or potassium ≤ 2.5 mmol/L during the first 7 days after randomization	First 7 days after enrollment

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: January 28, 2026
• First Submitted That Met QC Criteria: February 27, 2026
• First Posted (Actual): March 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: intensive care unit; Septic shock; Sepsis; hydrocortisone; Fludrocortisone; pilot
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Sepsis; Shock, Septic; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Pregnenediones; Pregnenes; Hydrocortisone; Fludrocortisone
• Other Study ID Numbers: 2024.398

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No