Traumatic Brain InjuryPhase 3Corti-TCNCT01093261
Corticosteroid Therapy for Glucocorticoid Insufficiency Related to Traumatic Brain Injury
A Phase 3 study testing Hydrocortisone Fludrocortisone in people with Traumatic Brain Injury and Trauma, run by Nantes University Hospital at 18 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 15 to 65 years
- Conditions the study is for
- Traumatic Brain Injury, Trauma, Adrenal Insufficiency
- What is being tested?
- Hydrocortisone Fludrocortisone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 336 participants
- Where
- 18 sitesFrance
- Study dates
- Aug 2010to Dec 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Trauma brain injury (Glasgow score below 8 and lesion on scanner)
- Informed consent
- Time to inclusion inferior to 24 hours
Who cannot join
- 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
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
France18 sites
University hospital
Amiens
University Hospital
Angers
University Hospital
Beaujon
University hospital
Bordeaux, 33000
University Hospital
Brest
Universtiy Hospital
Caen
University Hospital
Clermont-Ferrand
University hospital
Créteil, 94000
University Hospital
Créteil
University Hospital
Grenoble
University Hospital
Montpellier
University Hospital
Nantes
University Hospital
Nîmes
European Hospital Georges Pompidou
Paris, 75000
Saint Louis Hospital
Paris, 75000
University hospital
Poitiers, 86000
University Hospital
Strasbourg
University Hospital
Toulouse
About this study
Official title: Phase 3 Study of Hydrocortisone and Fludrocortisone in Glucocorticoid Insufficiency Related to Traumatic Brain Injury
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.
Read the 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.
- Conditions
- Traumatic Brain Injury, Trauma, Adrenal Insufficiency, Pneumonia
- Being tested
- Placebo, Hydrocortisone Fludrocortisone
- 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
- Medical subject headings
- Brain Injuries, Traumatic, Wounds and Injuries, Adrenal Insufficiency, Pneumonia, Multiple Trauma, Craniocerebral Trauma, Shock
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo:
continuous intra venous infusion of placebo n°1 for 10 days. enteral administration of placebo n°2 for 10 days.
Hydrocortisone FludrocortisoneDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| Hydrocortisone and fludrocortisone | Experimental | Patients with glucocorticoid insufficiency Receives: Drug: Hydrocortisone Fludrocortisone |
| Placebo | Placebo comparator | Patients with glucocorticoid insufficiency Receives: Drug: Placebo |
| Controlled | No intervention | Adapted glucocorticoid function |
What is being measured
The primary outcome is the main question the study is designed to answer.
rate of hospital acquired pneumonia
Presence of at least two signs (body fever greater than 38°C; leukocytosis greater than 12000/ml or leukopenia below 4000/ml, purulent pulmonary secretions) associated with the appearance of a new infiltrate or modification of an existing infiltrate on chest-X-ray. Confirmation by a lower respiratory tract sample using a quantitative culture with a predefined positive threshold. Hospital-acquired pneumonia was defined as a pneumonia that occurs 48 hours after admission, which was not incubating at time of admission (Am J Respir Crit Care Med 2005; 171, 388-416).
Measured: day-28
Secondary outcomes (10)
Neurological recovery
in adapated and insufficient glucocorticoid function (Glasgow Outcome Scale, Barthel index, MIF) (Ancillary study)
Measured: 1-year
other infections
Tracheobronchitis 1: Association of at least two signs (fever above 38.0°C, Leucocytosis above 12000/ml or purulent pulmonary secretions) with isolation of bacteria in a lower respiratory tract sample without modification of chest-X-Ray; Urinary tract infection : Fever above 38.2°C associated with leucocyturia (>10000/ml) and bacteriuria (>103 UFC/ml) without other infection; Bacteriemia : One positive blood culture (two positive blood cultures for Staphiloccocus coagulase negative); Surgical wound infection : sputum from surgical incision or scare dehiscence associated with fever.
Measured: day-28
Organ failures
Acute Lung Injury or Acute Respiratory Distress Syndrom: PaO2/FiO2 below 300 with bilateral infiltrates on chest-X-ray without elevation of left atrial pressure; Acute kydney injury: oliguria (<0.3 ml/kg/hour for 24 hours or more) or raise in basal creatinemia of more than 300%; Myocardial insufficiency: indexed cardiac output below 2 l/min/m2; Hematologic insufficiency: platelet count below 50 000/ml; Hepatic insufficiency: bilirubinemia (<50 mmol.l-1) with a prothrombin (<40%), SOFA score (First week)
Measured: day-28
Length of ICU stay
in adapated and insufficient glucocorticoid function
Measured: 6 months
Duration of mechanical ventilation support
in adapated and insufficient glucocorticoid function
Measured: 6 months
Mortality from all causes
in adapated and insufficient glucorticoid function
Measured: day-28
Mortality from all causes
in adapated and insufficient glucorticoid function
Measured: 1 year
Time to amines withdrawal
Measured: day-28
Post traumatic stress disorder
Assessment of psychological status (ancillary study)
Measured: 12 months
Glucocorticoid function
Short corticotropin test
Measured: on day 11-12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2010 (estimated)
- Study startAug 2010
- Primary completionNov 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 336 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Société Française d'Anesthésie et de Réanimation
- Responsible party
- Principal investigator, Karim ASEHNOUNE, Nantes University Hospital
- Investigators
- Karim ASEHNOUNE, Study chair, Nantes University HospitalAntoine ROQUILLY, Principal investigator, Nantes University HospitalPierre François Perrigault, Study director, CHU de MontpellierPierre Albaladejo, Study director, University Hospital, GrenobleMarc Leonne, Study director, CHU de MarseilleOlivier Langeron, Study director, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01093261
- Sponsor's protocol ID
- BRD/10/01-L
- Other IDs
- SFAR
- Acronym
- Corti-TC
- Status last verified
- Sep 2017
- First submitted
- 23 Mar 2010
- Last updated
- 14 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 21999663Asehnoune K, Seguin P, Allary J, Feuillet F, Lasocki S, Cook F, Floch H, Chabanne R, Geeraerts T, Roger C, Perrigault PF, Hanouz JL, Lukaszewicz AC, Biais M, Boucheix P, Dahyot-Fizelier C, Capdevila X, Mahe PJ, Le Maguet P, Paugam-Burtz C, Gergaud S, Plaud B, Constantin JM, Malledant Y, Flet L, Sebille V, Roquilly A; Corti-TC Study Group. Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial. Lancet Respir Med. 2014 Sep;2(9):706-16. doi: 10.1016/S2213-2600(14)70144-4. Epub 2014 Jul 24.
PubMed 25066331
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Study of Hydrocortisone and Fludrocortisone in Glucocorticoid Insufficiency Related to Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT01093261
- Acronym / sponsor ID
- Corti-TC / BRD/10/01-L
- Conditions
- Traumatic Brain Injury, Trauma, Adrenal Insufficiency, Pneumonia
- Keywords
- trauma, trauma brain injury, multiple trauma, head trauma, hydrocortisone, fludrocortisone, glucocorticoid insufficiency related to ICU, adrenal Insufficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 336 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Collaborators
- Société Française d'Anesthésie et de Réanimation
- Study start
- Aug 2010
- Primary completion
- Nov 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 25 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Hydrocortisone and fludrocortisone | Experimental | Drug: Hydrocortisone FludrocortisonePatients with glucocorticoid insufficiency |
| Placebo | Placebo comparator | Drug: PlaceboPatients with glucocorticoid insufficiency |
| Controlled | No intervention | –Adapted glucocorticoid function |
Who may qualify
- Ages
- 15 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Trauma brain injury (Glasgow score below 8 and lesion on scanner)
- Informed consent
- Time to inclusion inferior to 24 hours
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo: continuous intra venous infusion of placebo n°1 for 10 days. enteral administration of placebo n°2 for 10 days. | Drug | Placebo |
| Hydrocortisone FludrocortisoneHYDROCORTISONE: 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) | Drug | Hydrocortisone and fludrocortisone |
Primary outcome
rate of hospital acquired pneumonia
Time frame: day-28
Presence of at least two signs (body fever greater than 38°C; leukocytosis greater than 12000/ml or leukopenia below 4000/ml, purulent pulmonary secretions) associated with the appearance of a new infiltrate or modification of an existing infiltrate on chest-X-ray. Confirmation by a lower respiratory tract sample using a quantitative culture with a predefined positive threshold. Hospital-acquired pneumonia was defined as a pneumonia that occurs 48 hours after admission, which was not incubating at time of admission (Am J Respir Crit Care Med 2005; 171, 388-416).
10 secondary outcomes
Neurological recovery
Time frame: 1-year
other infections
Time frame: day-28
Organ failures
Time frame: day-28
Length of ICU stay
Time frame: 6 months
Duration of mechanical ventilation support
Time frame: 6 months
Mortality from all causes
Time frame: day-28
Mortality from all causes
Time frame: 1 year
Time to amines withdrawal
Time frame: day-28
Post traumatic stress disorder
Time frame: 12 months
Glucocorticoid function
Time frame: on day 11-12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2017.
- Background: PubMed 21999663Asehnoune 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.
- Derived from this study: PubMed 25066331Asehnoune K, Seguin P, Allary J, Feuillet F, Lasocki S, Cook F, Floch H, Chabanne R, Geeraerts T, Roger C, Perrigault PF, Hanouz JL, Lukaszewicz AC, Biais M, Boucheix P, Dahyot-Fizelier C, Capdevila X, Mahe PJ, Le Maguet P, Paugam-Burtz C, Gergaud S, Plaud B, Constantin JM, Malledant Y, Flet L, Sebille V, Roquilly A; Corti-TC Study Group. Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial. Lancet Respir Med. 2014 Sep;2(9):706-16. doi: 10.1016/S2213-2600(14)70144-4. Epub 2014 Jul 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karim ASEHNOUNE study chair
Nantes University Hospital
Antoine ROQUILLY principal investigator
Nantes University Hospital
Pierre François Perrigault study director
CHU de Montpellier
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydrocortisone Fludrocortisone in people with Traumatic Brain Injury and Trauma, run by Nantes University Hospital at 18 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
rate of hospital acquired pneumonia (time frame: day-28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01093261, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2017.