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.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 600
- 试验地点
- 1
- 主要终点
- Glasgow Scale Outcome Extended (GOSE).
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Only the pharmacist, who masks the capsules and labels the containers, will know the assignement of the codes, and will keep them blind until the last phase of the study, after the main statistical analysis, or when unmasking is required.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •-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.
排除标准
- •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.
研究组 & 干预措施
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
干预措施: Dexamethasone Oral (Drug)
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
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Glasgow Scale Outcome Extended (GOSE).
时间窗: one month
次要结局
- 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)
- Volume of pericontusional edema before and after 12 days of treatment in both groups of patients.(14 days)
- 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)
研究者
Jon Pérez Bárcena
MD
Hospital Son Espases