Hydrocortisone and Fludrocortisone for the Treatment of Septic Shock

Initiation of Hydrocortisone and Fludrocortisone in Adult Patients With Septic Shock：A Prospective Randomized Controlled Clinical Trial

The purpose of this study is to evaluate the efficacy and safety of the combination therapy of hydrocortisone and fludrocortisone among adult patients with septic shock.

Study Overview

• Status: Recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Hydrocortisone plus Fludrocortisone; Other: Standard care

Detailed Description

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and septic shock represents its most severe form, characterized by profound circulatory and metabolic abnormalities with high mortality.

Current international guidelines recommend intravenous hydrocortisone as adjunctive therapy in patients with septic shock who remain hypotensive despite adequate fluid resuscitation and vasopressor treatment. However, critically ill patients may exhibit relative deficiencies of both glucocorticoid and mineralocorticoid activity, and hydrocortisone alone may not fully meet the physiological demands under severe stress. In recent years, combination therapy with hydrocortisone and fludrocortisone has been investigated, but published trials have reported inconsistent results regarding mortality, shock reversal, and adverse events.

Therefore, this randomized controlled trial aims to evaluate the efficacy and safety of hydrocortisone combined with fludrocortisone, compared with standard therapy, in patients with septic shock.

• Study Type: Interventional
• Enrollment (Estimated): 336
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Qingquan Lyu, Master; Phone Number: 0086-18051063899; Email: bonhomie2014@163.com
• Study Contact Backup: Name: Xiaohua Gu, Master; Phone Number: 0086-18051062325; Email: njguxiaohua@163.com

Study Locations

• China
  • Jiangsu
    • Yangzhou, Jiangsu, China, 225000
      • Recruiting
      • Northern Jiangsu People's Hospital
      • Contact: Qingquan Lyu, Master; Phone Number: 0086-18051063899; Email: bonhomie2014@163.com
      • Contact: Xiaohua Gu, Master; Phone Number: 0086-18051062325; Email: njguxiaohua@163.com
      • Principal Investigator: Qingquan Lyu, Master
      • Sub-Investigator: Ruiqiang Zheng, Bachelor
      • Sub-Investigator: Jiangquan Yu, Doctor
      • Sub-Investigator: Xiaohua Gu, Master
      • Sub-Investigator: Ying Shi, Master
      • Sub-Investigator: Yuanjin Pan, Bachelor

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

(1)18≤Age≤90; (2)Diagnosis of septic shock within 12 h.

Exclusion Criteria:

Patients meeting any of the following conditions will be excluded:

1. Systemic corticosteroid therapy within the last 3 months before septic shock;
2. High-dose steroid therapy;
3. Immunosuppression;
4. Pregnant;
5. Known allergy to hydrocortisone or fludrocortisone;
6. Presence of gastrointestinal bleeding, perforation, or other conditions requiring fasting;
7. Anticipated death from a preexisting disease within 90 days after randomization (as determined by the enrolling physician);
8. Refusal of the attending staff or patient family;
9. Current participation in another clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydrocortisone plus Fludrocortisone; Hydrocortisone: 200 mg per day administered by continuous intravenous infusion for up to 7 days or until ICU discharge, whichever occurs first. Fludrocortisone: 50 μg administered orally or via nasogastric tube once daily for up to 7 days or until ICU discharge, whichever occurs first.	Drug: Hydrocortisone plus Fludrocortisone; Hydrocortisone will be administered at a dose of 200 mg per day by continuous intravenous infusion. Fludrocortisone will be administered at a dose of 50 μg once daily orally or via nasogastric tube. Both drugs will be given for up to 7 days or until ICU discharge, whichever occurs first.; Other Names: Hydrocortisone Injection; Fludrocortisone Acetate Tablets
Active Comparator: Standard care; Patients will receive standard care for septic shock according to current international guidelines, including fluid resuscitation, vasopressor therapy, antimicrobial treatment, and other supportive measures, including the use of hydrocortisone at the discretion of the treating physician, but without fludrocortisone.	Other: Standard care; Patients will receive standard care for septic shock according to current international and institutional guidelines, including fluid resuscitation, vasopressor therapy, antimicrobial treatment, and other supportive measures. Fludrocortisone will not be administered.Hydrocortisone may be administered at the discretion of the treating physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day mortality	All-cause mortality at day 90 after randomization	90 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day mortality	All-cause mortality at day 28 after randomization	28 days after randomization
ICU mortality	All-cause mortality at ICU discharge	From randomization to ICU discharge (up to 90 days)
Hospital mortality	All-cause mortality at hospital discharge	From randomization to hospital discharge (up to 90 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU-free days up to day 28	Total number of days alive and free of ICU stay during the 28 days after randomization.	28 days after randomization
CRRT-free days up to day 28	Total number of days alive and free of CRRT during the 28 days after randomization.	28 days after randomization
72h lactate	lactate level at 72h after randomization	72 hours after randomization
72h P/F	P/F at 72h after randomization	72 hours after randomization
Shock reversal time	Reversal of shock is defined as the maintenance of a systolic blood pressure of at least 90 mmHg without vasopressor support for at least 24 h. Time to shock reversal is defined as the time from randomization to shock reversal.	From randomization up to 28 days
ICU length of stay	Time in days until ICU discharge	From randomization to ICU discharge (up to 90 days)
Hospital length of stay	Time in days until hospital discharge	From randomization to hospital discharge (up to 90 days)
Change in Sequential Organ Failure Assessment (SOFA) score at 72 hours	The Sequential Organ Failure Assessment (SOFA) score ranges from 0 to 24, with higher scores indicating more severe organ dysfunction and worse clinical outcomes. The change in SOFA score (ΔSOFA) is calculated as the SOFA score at enrollment minus the SOFA score at 72 hours after randomization. If a patient is discharged from the ICU within 72 hours, the SOFA score at ICU discharge will be used for analysis.	72 hours after randomization
Vasopressor-free days up to day 28	Total number of days alive and free of vasopressor during the 28 days after randomization.	28 days after randomization
Ventilator support-free days up to day 28	Total number of days alive and free of ventilator support during the 28 days after randomization.	28 days after randomization

Collaborators and Investigators

• Sponsor: Northern Jiangsu People's Hospital
• Investigators: Principal Investigator: Qingquan Lyu, Master, Northern Jiangsu People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 25, 2026
• First Submitted That Met QC Criteria: February 1, 2026
• First Posted (Actual): February 3, 2026

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: septic shock; mortality; hydrocortisone; fludrocortisone
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Shock, Septic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Polycyclic Compounds; Quality Indicators, Health Care; Pregnanes; Steroids; Fused-Ring Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids; Hydrocortisone; Fludrocortisone; Standard of Care; fludrocortisone acetate
• Other Study ID Numbers: 2025ky387

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No