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

Phase 3

Not yet recruiting

• Conditions: Inflammation in Cardiac Surgery
• Interventions: Drug: hydrocortisone plus fludrocortisone; Drug: placebo of hydrocortisone plus fludrocortisone

• Registration Number: NCT07037043
• Lead Sponsor: Centre Hospitalier Universitaire, Amiens

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-06-17
• Study First Submitted QC: 2025-06-17
• Study First Posted: 2025-06-25
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-01
• Last Update Posted: 2025-07-02
• Study Start: 2025-08-01
• Primary Completion: 2028-05
• Study Completion: 2028-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 196

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
hydrocortisone plus fludrocortisone	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 of hydrocortisone plus fludrocortisone	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
variation of postoperative atrial fibrillation occurence between both groups	up to 7 days	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
variation of myocardial infarction occurence between both groups	up to 7 days	Myocardial infarction: defined according to the Fourth Universal Definition
variation of stroke occurence between both groups	up to 7 days	Stroke: defined as the sudden onset of a neurological deficit confirmed by brain imaging
Variation of total amount of norepinephrine between both groups	up to 7 days	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.
variation of occurrence of glucocorticoid side effect between both groups	up to 7 days	glucocorticoid side effects are hyperglycemia, hypernatremia and infections
Variation of 28-day mortality between both groups	at 28 days

Trial Locations

Locations (1)

CHRU Amiens; 🇫🇷 Amiens, France