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

NCT07037043 | Not Yet Recruiting Phase 3

• 1 other identifier: PI2024_843_0047
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 1

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

Keywords

Control of inflammation in cardiac surgery

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• variation of postoperative atrial fibrillation occurence between both groups

  up to 7 days

• variation of myocardial infarction occurence between both groups

  up to 7 days

• variation of stroke occurence between both groups

  up to 7 days

• Variation of total amount of norepinephrine between both groups

  up to 7 days

• variation of occurrence of glucocorticoid side effect between both groups

  up to 7 days

Study Arms (2)

hydrocortisone plus fludrocortisone

EXPERIMENTAL

* 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

placebo of hydrocortisone plus fludrocortisone

PLACEBO COMPARATOR

* 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

Interventions

hydrocortisone plus fludrocortisone 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

hydrocortisone plus fludrocortisone

placebo of hydrocortisone plus fludrocortisone 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

placebo of hydrocortisone plus fludrocortisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Centre Hospitalier Universitaire, Amiens: lead
• University Hospital, Rouen: collaborator
• University Hospital, Lille: collaborator

Study Sites (1)

CHRU Amiens

Amiens, 80480, France

Location

MeSH Terms

Interventions

Hydrocortisone; Fludrocortisone

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Central Study Contacts

Christophe Beyls, MD

CONTACT

(33)3 22 08 78 66; Beyls.christophe@chu-amiens.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2025
• First Posted: June 25, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 2, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)