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

NCT ID: NCT07037043

Last Updated: 2025-07-02

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 196 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-31
• Study Completion Date: 2028-06-30

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.

Conditions

Inflammation in Cardiac Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

hydrocortisone plus fludrocortisone

Intervention Type: DRUG

• 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 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

Group Type: PLACEBO_COMPARATOR

placebo of hydrocortisone plus fludrocortisone

Intervention Type: DRUG

• 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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Rouen

OTHER

Sponsor Role: collaborator

University Hospital, Lille

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire, Amiens

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHRU Amiens

Amiens, , France

Countries

France

Central Contacts

Christophe Beyls, MD

Role: CONTACT

Beyls.christophe@chu-amiens.fr

(33)3 22 08 78 66

Facility Contacts

Christophe Beyls, MD

Role: primary

Beyls.christophe@chu-amiens.fr

33+3 22 08 78 66

Other Identifiers

PI2024_843_0047

Identifier Type: -

Identifier Source: org_study_id