Corticosteroid Therapy for Glucocorticoid Insufficiency Related to Traumatic Brain Injury
Condition: Traumatic Brain Injury; Trauma; Adrenal Insufficiency; Pneumonia
MeSH terms: Pneumonia; Brain Injuries; Brain Injuries, Traumatic; Adrenal Insufficiency; Wounds and Injuries
Study type: Interventional
Phase: Phase 3

Summary: 
      Traumatic brained injured (TBI) patients frequently suffered from glucocorticoid
      insufficiency that is associated with a raise in the rate of pneumonia.

      In a placebo-controlled, multi-center, double-blinded trial, treatment of glucocorticoid
      insufficiency (hydrocortisone associated with fludrocortisone) will be assessed for
      prevention of post trauma pneumonia in a population of severe TBI patients.
    

Detailed description: 
      Treatment of glucocorticoid insufficiency in TBI patients remains controversial.

      The purpose of this study is to determine whether hydrocortisone associated with
      fludrocortisone decreases rate of hospital-acquired pneumonia on day-28 in TBI patients with
      glucocorticoid insufficiency. Glucocorticoid function will be assessed by a corticotropin
      test (ACTH 0.25 mg). The study treatment will be started before reception of the results of
      these test. Patients with glucocorticoid insufficiency (basal cortisolemia < 15 mcg/dl or
      post ACTH raise < or = 9 mcg/dl) will be treated for 10 days. Patients with adapted
      glucocorticoid function will no longer be treated till the results of corticotropin test are
      known.

      The primary end point will be rate of HAP on day-28 in patients with glucocorticoid
      insufficiency. Secondary endpoints will be neurological recovery (on day-28, -6 and -12),
      mortality (on day-28 and day-365), rate of other infections (on day-28), rate of organ
      failures (on day-28), mechanical ventilation weaning time, ICU length of stay.

      In a double-blinded fashion (randomized on a 1:1 basis), 326 patients receive 200 mg
      intravenously for 10 days. After 7 days, treatment will be tapered with 100 mg given
      intravenously for days 8-9, then 50 mg for day 10, and then stopped.

      All concomitant treatments, including antibiotics, fluids, vasopressors and ancillary
      therapies will be given at the discretion of the primary care physician. Evidence-based
      guidelines for the management of severe trauma brain injury (J Neurotrauma 2007; 24 Suppl 1,
      S1-106.) are encouraged to be followed. All institution are level I trauma center and
      university hospital.

      Clinical assessments were performed twice a day in the ICU. When HAP was suspected after
      clinical examination, a new infiltrate was checked on a chest X-ray. The study protocol
      stated that antibiotic therapy should not be modified before a bacteriological sample was
      performed

      All serious adverse events (SAE) which occur between days 0 and 28, which are unexpected
      and/or considered possibly or probably related to the study medication, must be documented
      and reported within 24 hours to the Safety and Efficacy Monitoring Committee. Non-serious
      adverse events will be listed on the case report form if they are unexpected and believed to
      be related to the study drug during days 0 to 14.

      Specific adverse events which will be monitored closely because of their relationship to
      corticosteroids and trauma are: Use of corticosteroids, i.e. gastrointestinal bleeding and
      superinfection; hyperglycemia, hypernatremia, muscular weakness, etc.

      In addition, substudies will include radiological assessment of hypothalamus and
      hypophyses,immune and neuro-endocrine interactions, post stress disorder assessment.
    

Intervention name(s): Placebo; Hydrocortisone Fludrocortisone
Intervention type(s): Drug; Drug
Intervention description(s): Placebo:
continuous intra venous infusion of placebo n°1 for 10 days. enteral administration of placebo n°2 for 10 days.; HYDROCORTISONE: 200 mg.day-1 for 7 days, 100 mg.day-1 on day 8 and 9, 50 mg on day-10 (continuous intravenous infusion) FLUDROCORTISONE: 50 microg.day-1 for 10 days (per os)
Intervention MeSH terms: Hydrocortisone; Fludrocortisone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: trauma; trauma brain injury; multiple trauma; head trauma; hydrocortisone; fludrocortisone; glucocorticoid insufficiency related to ICU; adrenal Insufficiency; pneumonia; intensive care unit; shock; neurological recovery