Using hydrocortisone and fludrocortisone to treat critical illness-related corticosteroid insufficiency

Hydrocortisone and Fludrocortisone for Critical Illness-related Corticosteroid Insufficiency

This study is testing if a combination of hydrocortisone and fludrocortisone can help critically ill ICU patients with low steroid levels breathe better and survive without needing extra medications.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 1092 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (other)
• Drugs / interventions: prednisone
• Locations: 1 site (Garches)
• Trial ID: NCT04404400 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness and safety of a combination of hydrocortisone and fludrocortisone compared to a placebo in adult ICU patients diagnosed with critical illness-related corticosteroid insufficiency (CIRCI). Patients with a SOFA score of 4 or higher will be screened for CIRCI and randomized to receive either the treatment or placebo. The study aims to determine if this combination can improve ventilation and vasopressor-free survival in these patients. Additionally, patients without CIRCI will receive standard care and be monitored over a 90-day period.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who are hospitalized in an ICU with a SOFA score of 4 or higher.

Not a fit: Patients with known chronic adrenal insufficiency or those experiencing septic shock may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and recovery outcomes for patients suffering from critical illness-related corticosteroid insufficiency.

How similar studies have performed: Previous studies have shown positive outcomes with corticosteroid treatments in septic shock, but this specific combination for CIRCI without septic shock is less explored.

Eligibility criteria

Inclusion Criteria:

* Adult (≥ 18 years);
* Hospitalized in an intensive care unit;
* SOFA score ≥ 4, for at least 6 consecutive hours;
* Informed written consent from patient or from legally authorized next of kin, or emergency deferred consent;
* Affiliation to a social security system or to a universal health coverage (Couverture Maladie Universelle, CMU).

Exclusion Criteria:

* Any suspected or proven acute adrenal insufficiency (As defined in international guidelines; basal cortisol \< 5 μg/dL or peak (60) cortisol \<18 μg/dL)
* Expected death or withdrawal of life-sustaining treatments within 48 hours
* Known chronic adrenal insufficiency
* Concomitant treatment that inhibits cortisol production
* Septic shock (Singer Jama 2016)
* Active tuberculosis or fungal infection
* Active viral hepatitis or active infection with herpes viruses
* Hypersensitivity or contraindication to hydrocortisone, fludrocortisone or Synacthène® or any of their excipients ( SmPC)
* Patient needing either anti-inflammatory corticosteroids or substitutive hydrocortisone for any reason (Such as those suffering from COVID-19 pneumonia requiring oxygen therapy).
* Current treatment by more than 15 mg/d of prednisone (or equivalent) for more than 30 days
* Diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome
* Pregnant or breastfeeding woman
* Moribund patient
* Previously enrolled in this study
* Participation to another interventional study that focuses on CIRCI and/or corticoid drugs and/or that addresses a similar primary endpoint as Hornbill ( ventilator- and vasopressor-free survival )
* Patient under guardianship or tutorship

Note: Included patients for whom acute adrenal insufficiency would be detected in the Synacthen ® test performed as part of the research for the diagnosis of CIRCI will not be randomized since they should be treated by corticosteroids.

Where this trial is running

Garches

• General Intensive care Unit, Raymond Poincaré Hospital, APHP — Garches, France (RECRUITING)

Study contacts

• Principal investigator: Nicholas HEMING, MD, PhD — General Intensive care Unit, Raymond Poincaré Hospital, APHP
• Study coordinator: Nicholas HEMING, MD, PhD

Conditions: Critical Illness Related Corticosteroids Insufficiency, critical illness related corticosteroids insufficiency, hydrocortisone, fludrocortisone, ICU, survival