Hydrocortisone Plus Fludrocortisone in High-risk Patients Undergoing for Cardiac Surgery (VASOCORT)

Cardiac surgery is a high-risk surgery and is associated with a rate of postoperative adverse outcomes. Like many others major surgery, cardiac surgery procedures induce a proinflammatory phase usually counterbalanced with an immunosuppressive phase so the immune response remained balanced.

In some cases, the immune response might be dysregulated with a more pronounced pro inflammatory state that compromises organ perfusion and with the occurrence of organ failure. From a mechanistic approach, the relationship between organ failure is complex and multifactorial with a high level of proinflammatory cytokines, a decrease in microcirculation, an endothelial dysfunction and an activation of coagulation and over. The clinical expression is an increase in vasopressor exposure and dose, an increase in mortality and in adverse outcomes with a predominance of acute kidney injury.

Various therapies have been assessed to manage cardiac surgery related sepsis including glucocorticoid therapy. Briefly, two major randomized trials assessed glucocorticoid therapy solely in scheduled cardiac surgery with cardiopulmonary bypass. No clinical benefit was demonstrated in term of reduction in postoperative mortality or adverse outcomes. Since, data support that the selection of patients at risk is crucial to demonstrate such a strategy. Indeed, data support that surprisingly some patients will have a very light immune response reflected by a low pro inflammatory cytokine.

The hypothesis is that the combination glucocorticoid and fludrocortisone could decrease adverse outcomes in selected patients.

Study Overview

• Status: Recruiting
• Conditions: Inflammation in Cardiac Surgery
• Intervention / Treatment: Drug: hydrocortisone plus fludrocortisone; Drug: placebo of hydrocortisone plus fludrocortisone

• Study Type: Interventional
• Enrollment (Estimated): 196
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Christophe Beyls, MD; Phone Number: (33)3 22 08 78 66; Email: Beyls.christophe@chu-amiens.fr

Study Locations

• France
  • Amiens, France, 80480
    • Recruiting
    • CHRU Amiens
    • Principal Investigator: Mouhamed Djahoum MOUSSA, MD
    • Principal Investigator: Emmanuel Besnier, MD
    • Sub-Investigator: Osama Abou Arab, Pr
    • Contact: Christophe Beyls, MD; Phone Number: 33+3 22 08 78 66; Email: Beyls.christophe@chu-amiens.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age > 18 years.
• Patient at intermediate/high risk (EuroSCORE II > 4%).

• Patient admitted for scheduled cardiac surgery:

  • Coronary artery bypass grafting (CABG).
  • Aortic valve replacement.
  • Mitral valve repair or replacement.
  • Surgery of the aortic root (aortic tube, Bentall procedure, Tirone David procedure, or other).
  • Combined surgery.
• Patient undergoing cardiopulmonary bypass (CPB).
• Informed consent signed by the patient.

Exclusion Criteria:

• Endocarditis
• Off-pump heart surgery
• Heart transplantation or long-term ventricular assist device (VAD)
• Emergency surgery: aortic dissection, emergency coronary artery bypass grafting (CABG)
• Failure to wean from CPB requiring short-term mechanical support (intra-aortic balloon pump, ECMO)
• Hypothermic surgery
• History of cardiac surgery
• Patient on long-term corticosteroid therapy
• Autoimmune disease or chronic inflammatory condition
• End-stage renal disease on long-term dialysis
• Contraindications to the administration of hydrocortisone and/or fludrocortisone according to the summary of product characteristics (SmPC)
• Pregnant or breastfeeding woman
• Patient under legal protection (guardianship, curators, or judicial safeguard).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hydrocortisone plus fludrocortisone; Hydrocortisone 200 mg/day for 5 days or until ICU discharge, starting at the initiation of cardiopulmonary bypass (CPB), administered intravenously via syringe pump in a double-blind manner; Fludrocortisone 50 µg/day in the morning for 5 days or until ICU discharge, administered orally or via nasogastric tube (if the patient is sedated), diluted in a glass of water, in a double-blind manner	Drug: hydrocortisone plus fludrocortisone; Hydrocortisone 200 mg/day for 5 days or until ICU discharge, starting at the initiation of cardiopulmonary bypass (CPB), administered intravenously via syringe pump in a double-blind manner; Fludrocortisone 50 µg/day in the morning for 5 days or until ICU discharge, administered orally or via nasogastric tube (if the patient is sedated), diluted in a glass of water, in a double-blind manner
Placebo Comparator: placebo of hydrocortisone plus fludrocortisone; Placebo for hydrocortisone (0.9% NaCl) administered following the same protocol as fludrocortisone in the intervention group; Placebo for fludrocortisone (capsule containing microcrystalline cellulose diluted in a glass of water) administered following the same protocol as fludrocortisone in the intervention group	Drug: placebo of hydrocortisone plus fludrocortisone; Placebo for hydrocortisone (0.9% NaCl) administered following the same protocol as fludrocortisone in the intervention group; Placebo for fludrocortisone (capsule containing microcrystalline cellulose diluted in a glass of water) administered following the same protocol as fludrocortisone in the intervention group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Variation of acute kidney injury occurence between both groups	up to 7 days
Variation of postoperative pulmonary complication occurrence between both groups	up to 7 days
Variation of number of norepinephrine requirement between both groups	up to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
variation of postoperative atrial fibrillation occurence between both groups	Postoperative atrial fibrillation: defined as a new-onset arrhythmia within 7 days after surgery, documented by an electrocardiogram showing absence of P waves and narrow, irregular QRS complexes	up to 7 days
variation of myocardial infarction occurence between both groups	Myocardial infarction: defined according to the Fourth Universal Definition	up to 7 days
variation of stroke occurence between both groups	Stroke: defined as the sudden onset of a neurological deficit confirmed by brain imaging	up to 7 days
Variation of total amount of norepinephrine between both groups	The total amount of norepinephrine will be expressed in milligrams and will correspond to the cumulative dose administered from ICU admission until the 7th postoperative day.	up to 7 days
variation of occurrence of glucocorticoid side effect between both groups	glucocorticoid side effects are hyperglycemia, hypernatremia and infections	up to 7 days
Variation of 28-day mortality between both groups		at 28 days

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire, Amiens
• Collaborators: University Hospital, Rouen; University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: June 17, 2025
• First Submitted That Met QC Criteria: June 17, 2025
• First Posted (Actual): June 25, 2025

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Control of inflammation in cardiac surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids; Hydrocortisone; Fludrocortisone
• Other Study ID Numbers: PI2024_843_0047

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