Corticosteroid Therapy for Glucocorticoid Insufficiency Related to Traumatic Brain Injury
Information source: Nantes University Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Traumatic Brain Injury; Trauma; Adrenal Insufficiency; Pneumonia
Intervention: Placebo (Drug); Hydrocortisone Fludrocortisone (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Nantes University Hospital Official(s) and/or principal investigator(s): Karim ASEHNOUNE, Study Chair, Affiliation: Nantes University Hospital Antoine ROQUILLY, Principal Investigator, Affiliation: Nantes University Hospital Pierre François Perrigault, Study Director, Affiliation: CHU de Montpellier Pierre Albaladejo, Study Director, Affiliation: University Hospital, Grenoble Marc Leonne, Study Director, Affiliation: CHU de Marseille Olivier Langeron, Study Director, Affiliation: Assistance Publique - Hôpitaux de Paris
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.
Clinical Details
Official title: Phase 3 Study of Hydrocortisone and Fludrocortisone in Glucocorticoid Insufficiency Related to Traumatic Brain Injury
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: rate of hospital acquired pneumonia
Secondary outcome: Neurological recoveryother infections Organ failures Length of ICU stay Duration of mechanical ventilation support Mortality from all causes Mortality from all causes Time to amines withdrawal Post traumatic stress disorder Glucocorticoid function
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.
Eligibility
Minimum age: 15 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Trauma brain injury (Glasgow score below 8 and lesion on scanner)
- Informed consent
- Time to inclusion inferior to 24 hours
Exclusion Criteria:
- Tetraplegia
- Administration of chronic corticosteroids in the last 6 months or acute steroid
therapy (any dose) within 4 weeks (excluding inhaled steroids). Topical steroids are
not exclusions
- Drug-induced immunosuppression, including chemotherapy or radiation therapy within 4
weeks before the study
- Antibiotherapy for active sepsis at the time of inclusion
Locations and Contacts
University hospital, Amiens, France
University Hospital, Angers, France
University Hospital, Beaujon, France
University hospital, Bordeaux 33000, France
University Hospital, Brest, France
Universtiy Hospital, Caen, France
University Hospital, Clermont Ferrand, France
University Hospital, Creteil, France
University hospital, Creteil 94000, France
University Hospital, Grenoble, France
University Hospital, Montpellier, France
University Hospital, Nantes, France
University Hospital, Nimes, France
European Hospital Georges Pompidou, Paris 75000, France
Saint Louis Hospital, Paris 75000, France
University hospital, Poitiers 86000, France
University Hospital, Strasbourg, France
University Hospital, Toulouse, France
Additional Information
Related publications: Asehnoune K, Roquilly A, Sebille V; Corti-TC trial group. Corticotherapy for traumatic brain-injured patients--the Corti-TC trial: study protocol for a randomized controlled trial. Trials. 2011 Oct 14;12:228. doi: 10.1186/1745-6215-12-228.
Starting date: August 2010
Last updated: December 12, 2012
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