Dexamethasone for the Treatment of Vasogenic Pericontusional Edema. (DEXCON-TBI)

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Traumatic Brain Injury; Cerebral Edema
• Intervention / Treatment: Drug: Dexamethasone Oral; Drug: Placebo oral tablet

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jon Perez-Barcena, MD-PhD; Phone Number: 75974 +34 871 205000; Email: juan.perez@ssib.es

Study Locations

• Spain
  • Balearic Islands
    • Palma De Mallorca, Balearic Islands, Spain, 07120
      • Recruiting
      • Hospital Universitari Son Espases
      • Contact: Jon Perez Barcena, MD PhD; Phone Number: 75974 +34 871 205000; Email: juan.perez@ssib.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexamethasone; 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). Dexamethasone (Fortecortin®) will be acquired from ERN, SA. Laboratories (Barcelona, Spain). The Son Espases Pharmacy Department will be in charge of developing and conditioning the 4mg, 2mg and 1mg dexamethasone / placebo capsules needed for 12 days of treatment, keeping the researchers blind	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 Comparator: Control; The preparation and conditioning of the 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). The Son Espases Pharmacy Department will be responsible for identifying the containers and sending them by courier to the participating hospitals. A record of the dispensing of test samples will be kept and will be sent in acknowledgment of receipt for control	Drug: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Glasgow Scale Outcome Extended (GOSE).	one month

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of episodes of neurological deterioration in both groups of patients during the 12 days of treatment.	14 days
Symptoms associated with TBI in both groups of patients during the 12 days of treatment.	14 days
Volume of pericontusional edema before and after 12 days of treatment in both groups of patients.	14 days
Presence of adverse events between the two groups during the 12 days of treatment.	14 days
Neuropsychological tests between the two groups of patients one month and 6 months after the TBI.	one month

Collaborators and Investigators

• Sponsor: Hospital Son Espases

Publications and helpful links

General Publications

• Moll A, Lara M, Pomar J, Orozco M, Frontera G, Llompart-Pou JA, Moratinos L, Gonzalez V, Ibanez J, Perez-Barcena 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.
• Lara M, Moll A, Mas A, Picado MJ, Gassent C, Pomar J, Llompart-Pou JA, Brell M, Ibanez J, Perez-Barcena J. Use of diffusion tensor imaging to assess the vasogenic edema in traumatic pericontusional tissue. Neurocirugia (Astur : Engl Ed). 2020 Jul 21:S1130-1473(20)30080-4. doi: 10.1016/j.neucir.2020.05.002. Online ahead of print. English, Spanish.
• Pérez-Bárcena J, Castaño-León AM, Lagares Gómez-Abascal A, Barea-Mendoza JA, Navarro Maín B, Pomar Pons J, Periañez Párraga LDM, Ibáñez Domínguez J, Chico-Fernández M, Llompart-Pou JA, Frontera Juan G; DEXCON TBI trial collaborators. 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. Medicine (Baltimore). 2021 Jan 22;100(3):e24206. doi: 10.1097/MD.0000000000024206.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2020
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: March 5, 2020
• First Submitted That Met QC Criteria: March 9, 2020
• First Posted (Actual): March 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 23, 2020
• Last Update Submitted That Met QC Criteria: November 19, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: edema; injury; brain; steroids; traumatic; contusion
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Edema; Brain Edema; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: eudraCT: 2019-004038-41

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No