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

Centre Hospitalier Universitaire, Amiens

Status and phase: Not yet enrolling; Phase 3

Conditions: Inflammation in Cardiac Surgery

Treatments: Drug: hydrocortisone plus fludrocortisone; Drug: placebo of hydrocortisone plus fludrocortisone

Study type: Interventional

Funder types: Other

Identifiers

NCT07037043

PI2024_843_0047

Details and patient eligibility

About

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.

Enrollment: 196 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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196 participants in 2 patient groups, including a placebo group

hydrocortisone plus fludrocortisone

Experimental group

Description:

* 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

Treatment:

Drug: hydrocortisone plus fludrocortisone

placebo of hydrocortisone plus fludrocortisone

Placebo Comparator group

Description:

* 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

Treatment:

Drug: placebo of hydrocortisone plus fludrocortisone