HORNbILL: Hydrocortisone and Fludrocortisone for Critical Illness-related Corticosteroid Insufficiency

Sponsor
Assistance Publique - Hôpitaux de Paris (Other)
Overall Status
Recruiting
CT.gov ID
NCT04404400
Collaborator
(none)
1,092
1
2
48
22.8

Study Details

Study Description

Brief Summary

The study aims at assessing the efficacy and the safety of hydrocortisone combined with fludrocortisone compared to placebo in ICU adults with critical illness related corticosteroid insufficiency.

Condition or Disease Intervention/Treatment Phase
  • Drug: Investigational products administration
  • Drug: Placebo administration
Phase 3

Detailed Description

The hypothalamic-pituitary-adrenal axis together with the noradrenergic/vasopressinergic system are the main systems of host response to stress. In 2008 the scientific community described a syndrome called critical illness related corticosteroids insufficiency (CIRCI) in which body homeostasis is lost owing to insufficient cortisol production or bioactivity in tissues. Recent updates of international guidelines have spelled out the pathophysiology, diagnosis and management of CIRCI. The prevalence of CIRCI varies according to case mix and severity of illness. The combination of hydrocortisone and fludrocortisone improved outcomes in septic shock, a condition often complicated with CIRCI. However, there is insufficient evidence on the efficacy of corticosteroids in patients with CIRCI and without septic shock. The hypothesis of the study is that the hydrocortisone-fludrocortisone association will improve ventilation and vasopressor free survival in ICU patients with Critical illness related Corticosteroid Insufficiency.

Patients with a SOFA score ≥ 6 will be screened for CIRCI. Patients suffering from CIRCI will be randomized to receive hydrocortisone and fludrocortisone or their placebo. Patients without CIRCI will receive standard of care and will be followed up during 90 days (cohort-observational study).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
1092 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Hydrocortisone and Fludrocortisone for Critical Illness-related Corticosteroid Insufficiency
Actual Study Start Date :
Feb 2, 2022
Anticipated Primary Completion Date :
Feb 1, 2026
Anticipated Study Completion Date :
Feb 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Active

For CIRCI patients: hydrocortisone + fludrocortisone therapy.

Drug: Investigational products administration
Investigational products include: Hydrocortisone hemisuccinate 50 mg: one intravenous injection every 6 hours, and 9 alpha fludrocortisone 50 μg: one tablet per day via a nasogastric tube. All treatments will be stopped after 7 days or until the patient has left the intensive care unit (whichever occurs first) without tapering off.

Placebo Comparator: Placebo

For CIRCI patients: hydrocortisone placebo + fludrocortisone placebo

Drug: Placebo administration
Placebos for hydrocortisone and for fludrocortisone, administered in same manner as the active drugs in the interventional arm, for 7 days.

Outcome Measures

Primary Outcome Measures

  1. Ventilation and vasopressors free survival [at day 90]

    Proportion of 90-Day ventilation and vasopressors free survival, which is a composite of proportion of survivors at day 90 and of patients without new onset of ventilation or vasopressors in the 28 days after randomisation

Secondary Outcome Measures

  1. Mortality rates [at day 28, 90 and 180]

    Mortality rates at ICU and hospital discharge and at day 28, 90 and 180 after randomization

  2. Number of days alive without vasopressors [at day 28 and 90]

    Number of days alive without vasopressors on day 28 and day 90 after randomization.

  3. Number of days alive free of mechanical ventilation [at day 28 and 90]

    Number of days alive free of mechanical ventilation on day 28 and day 90 after randomization.

  4. Number of days alive with SOFA <6 [daily un to 28 days]

    Number of days alive with SOFA <6 in the 28 days after randomization

  5. Withhold and/or withdraw proportion [up to 3 months]

    Proportion of patients with a decision to withhold and/or withdraw active treatments.

  6. ICU duration [up to 3 months]

    Duration of stay (unit: day and minutes) at ICU.

  7. duration of hospitalization of stay [daily up to 28 days]

    Duration of hospitalization of stay.

  8. Rate of re-admission to the ICU [daily up to 28 days]

    Rate of re-admission to the ICU during the 28 days after randomization.

  9. Proportion of patients affected by any serious adverse events associated with corticosteroids [daily up to 28 days]

    Proportion of patients affected by any serious adverse events associated with corticosteroids, among the following: hospital-acquired infections, hyperglycemia, hypernatremia, neurological disorders (coma, stroke or muscle weakness) during the 28 days after randomization; patients affected by hospital-acquired infections; episodes of hyperglycemia during ICU stay or up to day 28; episodes of hypernatremia during ICU stay or up to day 28; gastroduodenal bleeding requiring transfusion or hemostatic treatment during ICU stay (or up to day 28, whichever occurs first).

  10. Rate of ventilation and vasopressors free survival at day 90 [at day 90]

    Secondary endpoint concerning screened but non-randomised patients: Rate of ventilation and vasopressors free survival at day 90 in subjects devoid of CIRCI

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • ≥ 18 years;

  • Hospitalized in an intensive care unit;

  • SOFA score ≥ 6, for at least 6 consecutive hours;

  • Informed written consent from patient or from legally authorized next of kin, or emergency deferred consent.

Exclusion Criteria:
  • Septic shock;

  • Active tuberculosis or fungal infection;

  • Active viral hepatitis or active infection with herpes viruses;

  • Hypersensitivity to corticosteroids;

  • Patient requiring corticosteroids;

  • Current treatment by more than 15 mg/d of prednisone (or equivalent) for more than 30 days;

  • Pregnant or breastfeeding woman;

  • Moribund patient;

  • Persons without social security;

  • Under guardianship.

Contacts and Locations

Locations

Site City State Country Postal Code
1 General Intensive care Unit, Raymond Poincaré Hospital, APHP Garches France 92380

Sponsors and Collaborators

  • Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Nicholas HEMING, MD, PhD, General Intensive care Unit, Raymond Poincaré Hospital, APHP
  • Study Director: Djillali ANNANE, MD, PhD, General Intensive care Unit, Raymond Poincaré Hospital, APHP

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT04404400
Other Study ID Numbers:
  • APHP200018
  • 2020-003942-35
First Posted:
May 27, 2020
Last Update Posted:
Feb 10, 2022
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Assistance Publique - Hôpitaux de Paris
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 10, 2022