Clinical Trial Results:
Traitement de l'insuffisance surrénale secondaire à un traumatisme crânien grave.
Etude multicentrique, contrôlée, randomisée portant sur un médicament.
- Etude Corti-TC"
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Summary
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EudraCT number |
2010-019178-33 |
Trial protocol |
FR |
Global end of trial date |
06 Dec 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Sep 2022
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First version publication date |
08 Sep 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BRD/10/1-L
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01093261 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
CHU de Nantes
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Sponsor organisation address |
5 allée de l'ile gloriette, Nantes, France,
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Public contact |
Anne Omnes, CHU de Nantes, +33 0253482835, bp-prom-regl@chu-nantes.fr
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Scientific contact |
Anne Omnes, CHU de Nantes, +33 0253482835, bp-prom-regl@chu-nantes.fr
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Aug 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Dec 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Dec 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
L’objectif principal est de tester, dans une population de patients traumatisés crâniens l’efficacité d’un traitement de l’IS par hydrocortisone et fludrocortisone sur la prévention des pneumopathies nosocomiales à J28.
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Protection of trial subjects |
Patients were informed in complete and faithful terms and in understandable language of the objectives and constraints of the study, the potential risks, the required observation and safety measures, and their right to refuse to participate in the study or to revoke their consent at any time.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Aug 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 328
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Worldwide total number of subjects |
328
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EEA total number of subjects |
328
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
328
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||
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Pre-assignment
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Screening details |
The recruitment is carried out from the hospital reception of head trauma patients with severity criteria. According to the local organization of the investigating centers, the selection took place: in the emergency department or in the anesthesia and intensive care department. | |||||||||
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Period 1
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Period 1 title |
Period 1 (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator | |||||||||
Blinding implementation details |
treatment versus Placebo
All members of the surgical unit, including the anesthesiologist and surgeon, will remain blind to the assigned treatment group as well as the patient
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Treatment | |||||||||
Arm description |
Hydrocortisone : ivse : 200 mg/j pendant 10 jours + po :fludrocortisone 50 microg/j. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Hydrocortisone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for concentrate for solution for infusion
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Routes of administration |
Concentrate for solution for infusion
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Dosage and administration details |
Continuous intravenous administration at a dose of 200 mg/day for 10 days
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Investigational medicinal product name |
Fludrocortisone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Buccal tablet
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Routes of administration |
Buccal use
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Dosage and administration details |
The dose of 50 µg / day during the stay in intensive care (10 days maximum)
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Arm title
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Placebo | |||||||||
Arm description |
Excipients : phosphate disodique, phosphate monosodique | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo de l'hydrocortisone : phosphate disodique, phosphate monosodique
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for concentrate for solution for infusion
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Routes of administration |
Concentrate for solution for infusion
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Dosage and administration details |
Continuous intravenous administration at a dose of 200 mg/day
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Investigational medicinal product name |
Placebo de la Fludrocortisone : cellulose microcristalline, magnésium stéarate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Buccal tablet
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Routes of administration |
Buccal use
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Dosage and administration details |
Once-daily enteral administration
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Baseline characteristics reporting groups
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Reporting group title |
Period 1 (overall period)
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Groupe treatment
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The main analysis of the primary outcome used a multivariate Cox proportional hazards model that included 2 predefined covariates: mechanism, Glasgow coma score, age, and arterial pressure (MGAP) score and Glasgow Coma Scale (GCS) score.
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Subject analysis set title |
Traitement placebo
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The main analysis of the primary outcome used a multivariate Cox proportional hazards model that included 2 predefined covariates: mechanism, Glasgow coma score, age, and arterial pressure (MGAP) score and Glasgow Coma Scale (GCS) score.
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End points reporting groups
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Reporting group title |
Treatment
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Reporting group description |
Hydrocortisone : ivse : 200 mg/j pendant 10 jours + po :fludrocortisone 50 microg/j. | ||
Reporting group title |
Placebo
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Reporting group description |
Excipients : phosphate disodique, phosphate monosodique | ||
Subject analysis set title |
Groupe treatment
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The main analysis of the primary outcome used a multivariate Cox proportional hazards model that included 2 predefined covariates: mechanism, Glasgow coma score, age, and arterial pressure (MGAP) score and Glasgow Coma Scale (GCS) score.
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Subject analysis set title |
Traitement placebo
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The main analysis of the primary outcome used a multivariate Cox proportional hazards model that included 2 predefined covariates: mechanism, Glasgow coma score, age, and arterial pressure (MGAP) score and Glasgow Coma Scale (GCS) score.
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End point title |
hazard ratio for HAP at day 28 | |||||||||
End point description |
The first primary endpoint was the comparison of the rates of Nosocomial Pneumonia in the first 28 days after the trauma, i.e., during the period most at risk of developing this complication, between the two groups (hydrocortisone + fludrocortisone versus double placebo) in patients with adrenal insufficiency criteria.
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End point type |
Primary
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End point timeframe |
28 days
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Statistical analysis title |
Rates of Nosocomial Pneumonia in the first 28 days | |||||||||
Statistical analysis description |
The final analysis will be conducted on a modified intention-to-treat (mITT) basis and will be performed as soon as the study has been stopped. It will be performed only on patients with criteria of adrenal insufficiency at the initial assessment. The mITT analysis is therefore defined a priori and is made necessary by the urgency of initiating study treatment when the results of the hormonal assessment are not yet available. results of the hormonal assessment are only obtained in 48 hours.
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Comparison groups |
Groupe treatment v Traitement placebo
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Number of subjects included in analysis |
328
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
= 0.07 | |||||||||
Method |
Regression, Cox | |||||||||
Parameter type |
Cox proportional hazard | |||||||||
Point estimate |
0.75
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.55 | |||||||||
upper limit |
1.03 | |||||||||
Variability estimate |
Standard deviation
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Adverse events information
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Timeframe for reporting adverse events |
They should be reported immediately (within 24 hours of its detection by the investigator) to the sponsor.
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Adverse event reporting additional description |
Annual safety report once a year.
Pregnancy, overdose, misuse, errors or risk of medication errors make the subject of a report to the sponsor by the investigator even if there are no adverse reactions.
Some non-serious adverse events may be declared to the proponent (--> protocole).
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15
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Reporting groups
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Reporting group title |
Traitement
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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24 Aug 2010 |
Adding centers |
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22 Feb 2011 |
Adding centers |
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31 May 2011 |
Adding centers |
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25 Oct 2011 |
Adding centers |
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29 Nov 2011 |
Suppression of centers |
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21 Jun 2012 |
Study extension |
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23 Oct 2012 |
Change of investigators |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/25066331 |
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