Dexamethasone for the Treatment of Vasogenic Pericontusional Edema.

Traumatic Brain Injury Clinical Trial

— DEXCON-TBI  

Official title:

Dexamethasone for the Treatment of Traumatic Brain Injured Patients With Brain Contusions and Pericontusional Edema: Study Protocol for a Prospective, Randomized and Double Blind Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04303065
• Other study ID #: eudraCT: 2019-004038-41
• Status: Recruiting
• Phase: Phase 3
• Start date: July 24, 2020
• Est. completion date: February 1, 2024

Study information

• Verified date: November 2020
• Source: Hospital Son Espases
• Contact: Jon Perez-Barcena, MD-PhD
• Phone: +34 871 205000
• Email: juan.perez[@]ssib.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The DEXCON-TBI trial is a multicenter, pragmatic, randomized, triple-blind, placebo controlled trial to quantify the effects of the administration of dexamethasone on the prognosis of TBI patients with brain contusions and pericontusional edema. Adult patients who fulfil the elegibility criteria will be randomized to receive dexamethasone or placebo. Patients who have suffered a head injury and have one or more cerebral contusions with visible pericontusional edema in the CT scan can be included in the study. The doses of dexamethasone will be a short and descending course: 4mg/6 hours (2 days); 4 mg/8 hours (2 days); 2 mg/6 hours (2 days); 2 mg/8 hours (2 days); 1 mg/8 hours (2 days); 1 mg/12 hours (2 days). The primary outcome is the Glasgow Scale Outcome Extended (GOSE) performed one month and 6 months after trauma. Other secondary outcomes are: compare the number of episodes of neurological deterioration; compare the symptoms associated with TBI; compare the presence of adverse events during treatment; compare the volume of pericontusional edema before and after 12 days of treatment in both groups of patients; and compare the results of the neuropsychological tests between the two groups of patients one month and 6 months after the TBI. The main analysis will be on an ''intention-to-treat´´ basis. A descriptive analysis of the baseline variables will be made for each treatment group. Logistic regression will be used to estimate the effect of dexamethasone and placebo on GOSE at one month and at 6 months, dichotomized in unfavorable outcome (GOSE 1-6) and favorable outcome (GOSE 7-8). Since the severity of the initial injury will determine significantly the final outcome of the patient, to assess the effect of dexamethasone, efficacy will also be analyzed using the 'sliding dichotomy'. A subgroup analysis will be carried out by stratifying the patients as they present more or less than 10mL of pericontusional edema in the preinclusion CT. We will perform an interim analysis with the patients included during the first year to calculate the conditional power. An independent statistician will blindly perform this analysis. At the same time a safety analysis will be also perfomed. A study with 600 patients would have about 80% power (two sided alpha=5%) to detect a 12% absolute increased (from 50% to 62%) in good outcome.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: February 1, 2024
• Est. primary completion date: September 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• -Patients who have suffered a head injury and have one or more cerebral contusions with visible pericontusional edema in the CT scan.

• Patients with brain contusions in whom non-sugical treatment has been selected initially.

• Age 18 or over and under 85

• Signing of informed consent by the patient or by his legal representative. The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use dexamethasone in a particular patient with TBI. This pragmatic approach will allow us to see whether the intervention improves patient outcomes under real-life conditions.

Exclusion Criteria:

• Patients with TBI and brain contusions who have required surgery to evacuate the cerebral contusion before randomization.

• Patients with TBI who have required a craniotomy before randomization for any other reason: evacuation of subdural, epidural hematoma or depressed skull fracture.

• Patients with an extracranial Injury Severity Score greater than 18 points.

• Patients in whom the use of corticosteroids is contraindicated.

• Patients who take oral corticosteroids chronically.

• Patients included in another clinical trial.

• Known intolerance or hypersensitivity to dexamethasone.

• Patients with allergy or intolerance to the following excipients contained in dexamethasone / placebo capsules: lactose, corn starch or microcrystalline cellulose.

• Patients with a history of psychotic disorders.

• Patients with inability to take medication orally due to swallowing problems in which it is not indicated to place a nasogastric tube.

• Pregnant or breastfeeding patients.

• Patients in a GCS 3 points situation with bilateral dilated pupils.

• Patients with associated spinal cord injuries.

• Patient with any systemic condition that contraindicates the use of corticosteroids.

Related Conditions & MeSH terms

• Brain Edema
• Brain Injuries
• Brain Injuries, Traumatic
• Cerebral Edema
• Edema
• Traumatic Brain Injury

Intervention

Drug:
• Dexamethasone Oral
It will be a short and descending course of oral dexamethasone: 4mg/6 hours (2 days); 4 mg/8 hours (2 days); 2 mg/6 hours (2 days); 2 mg/8 hours (2 days); 1 mg/8 hours (2 days); 1 mg/12 hours (2 days).
• Placebo oral tablet
The preparation and conditioning of the placebo capsules will be carried out following the standardized work procedures of the pharmaceutical laboratory and its quality controls, previously authorized by the Agencia Española del Medicamento (AEMPS).

Locations

Country	Name	City	State
Spain	Hospital Universitari Son Espases	Palma De Mallorca	Balearic Islands

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Son Espases

Country where clinical trial is conducted

Spain, 

References & Publications (2)

Lara M, Moll A, Mas A, Picado MJ, Gassent C, Pomar J, Llompart-Pou JA, Brell M, Ibáñez J, Pérez-Bárcena J. Use of diffusion tensor imaging to assess the vasogenic edema in traumatic pericontusional tissue. Neurocirugia (Astur). 2020 Jul 21. pii: S1130-1473(20)30080-4. doi: 10.1016/j.neucir.2020.05.002. [Epub ahead of print] English, Spanish. — View Citation

Moll A, Lara M, Pomar J, Orozco M, Frontera G, Llompart-Pou JA, Moratinos L, González V, Ibáñez J, Pérez-Bárcena J. Effects of dexamethasone in traumatic brain injury patients with pericontusional vasogenic edema: A prospective-observational DTI-MRI study. Medicine (Baltimore). 2020 Oct 23;99(43):e22879. doi: 10.1097/MD.0000000000022879. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glasgow Scale Outcome Extended (GOSE).		one month
Secondary	Number of episodes of neurological deterioration in both groups of patients during the 12 days of treatment.		14 days
Secondary	Symptoms associated with TBI in both groups of patients during the 12 days of treatment.		14 days
Secondary	Volume of pericontusional edema before and after 12 days of treatment in both groups of patients.		14 days
Secondary	Presence of adverse events between the two groups during the 12 days of treatment.		14 days
Secondary	Neuropsychological tests between the two groups of patients one month and 6 months after the TBI.		one month