Phase 3 Study of Hypertonic Resuscitation Following Severe Traumatic Brain Injury (TBI)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 1,331
- 试验地点
- 12
- 主要终点
- Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Completer Analysis
研究概览
简要总结
The purpose of this study is to determine if hypertonic saline with and without dextran can improve neurologic outcomes in victims of severe traumatic brain injury (TBI).
Injury and lost blood from trauma can cause your body to go into shock (low blood pressure related to blood loss). This decreased blood flow can lead to organ damage. In order to restore the blood pressure and blood flow, the medics give fluids into the patients' veins as soon as possible. This is called "resuscitation". The fluid most commonly used is "isotonic" or one that is the same salt concentration as the blood. The investigators are trying to determine if infusing a "hypertonic" fluid or one more concentrated than the blood can increase the blood pressure and restore blood flow more efficiently. The hypertonic fluids they are using are called hypertonic saline with dextran (HSD) and hypertonic saline (no dextran). Hypertonic saline is a salt solution that is slightly more concentrated than blood. Dextran is a sugar solution.
详细描述
To determine if prehospital administration of 7.5% Hypertonic Saline in 6% Dextran-70 (HSD) OR 7.5% Hypertonic Saline (HS) compared to current standard therapy with NS as an initial resuscitation fluid affects neurological outcome following severe traumatic brain injury.
Trauma is the leading cause of death among North Americans between the ages of 1 and 44 years. The majority of these deaths result from hypovolemic shock or severe brain injury. Patients in hypovolemic shock develop a state of systemic tissue ischemia then a subsequent reperfusion injury at the time of fluid resuscitation. Conventional resuscitation involves the IV administration of a large volume of isotonic or slightly hypotonic (lactated ringers, LR) solutions beginning in the pre-hospital setting. Although not conclusive, prior studies have suggested that alternative resuscitation with hypertonic saline (7.5%) solutions may reduce morbidity or mortality in these patients. Furthermore, hypertonic fluids may have specific advantages in the brain-injured patient, as they may aid in the rapid restoration of cerebral perfusion and prevent extravascular fluid sequestration, thereby limiting secondary brain injury. In addition, recent studies have demonstrated that hypertonicity significantly alters the activation of inflammatory cells, an effect that may reduce subsequent organ injury from ischemia-reperfusion and decrease nosocomial infection.
This study is a randomized, double-blind, three-arm placebo controlled trial designed to evaluate the clinical outcome of trauma patients with severe TBI as manifested by a pre-hospital GCS of 8 or less. Patients will be randomized to a single 250cc IV dose of 7.5% saline in 6% Dextran-70 (HSD), 7.5% saline (HS) or normal saline as the initial fluid for pre-hospital resuscitation. No additional interventions will occur once the patient is admitted to the hospital. In hospital data collection will last up to 28 days. Patients will have neurologic outcome measurements at discharge, 1 month post discharge, and 6 months post injury. Enrollment will be restricted to age ≥ 15 years or ≥ 50 kg if age is unknown.
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)
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Blunt trauma
- •Pre-hospital Glasgow Coma Scale equal to or less than 8(GCS≤8)*
- •Age 15 years or older or 50 kg or more
- •Patients who met the inclusion criteria above and did not meet the exclusion criteria below but who had systolic blood pressure (SBP) ≤70 or SBP>70 and SBP≤90 and heart rate (HR)≥108 were included in the Hypertonic Resuscitation following Traumatic Injury study that focused on shock patients who may or may not have a traumatic brain injury (TBI). In other words, patients with both TBI and shock would not be included in this study of TBI patients without shock at the time of enrollment.
排除标准
- •Known or suspected pregnancy
- •Age younger than 15 years or less than 50 kg if age unknown
- •Ongoing pre-hospital cardiopulmonary resuscitation (CPR)
- •Administration of more than 2L crystalloid or any colloid or blood products
- •Severe hypothermia (T less than 28C)
- •Drowning or asphyxia due to hanging
- •Burns TBSA more than 20%
- •Isolated penetrating injury to the head
- •Inability to obtain pre-hospital intravenous access
- •Time of call received at dispatch to study intervention more than four hours
- •Known prisoners
研究组 & 干预措施
7.5% hypertonic saline/6% dextran (HSD)
250 ml intravenous bolus administration of 7.5% saline/6% dextran 70
干预措施: 7.5% Hypertonic Saline in 6% Dextran-70 (HSD) (Drug)
7.5% hypertonic saline (HS)
250 ml intravenous bolus administration of 7.5% hypertonic saline
干预措施: 7.5% Hypertonic Saline (HS) (Drug)
0.9% normal saline (NS)
250 ml intravenous bolus administration of 0.9% saline
干预措施: 0.9% Normal Saline (NS) (Drug)
结局指标
主要结局
Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Completer Analysis
时间窗: 6 months after injury
Glasgow outcome score extended (GOSE) contains eight categories: 1. Dead, 2. Vegetative State (VS), 3. Lower Severe Disability (Lower SD), 4. Upper Severe Disability (Upper SD), 5. Lower Moderate Disability (Lower MD), 6. Upper Moderate Disability (Upper MD), 7. Lower Good Recovery (Lower GR) and 8. Upper Good Recovery (Upper GR). A measured neurological outcome of GOSE≤4 is a poor outcome of severe disability, vegetative state, or death. Completer analysis includes only those patients with GOSE completed at 6 months after injury.
Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Imputed Analysis
时间窗: 6 months after injury
Glasgow outcome score extended (GOSE) contains 8 categories: 1. Dead, 2. Vegetative State, 3. Lower Severe Disability, 4. Upper Severe Disability, 5. Lower Moderate Disability, 6. Upper Moderate Disability, 7. Lower Good Recovery and 8. Upper Good Recovery. To adjust for 15% of subjects with absent 6-month GOSE data, an analysis using 20 hot deck imputations for the 6-month GOSE was done using data from patients who were discharged alive based on 1-month post discharge GOSE data or discharge GOSE (if 1-month post discharge data were not available), length of hospital stay, and treatment group.
次要结局
- Subgroup of Participants With Head Abbreviated Injury Scores (AIS) Greater Than or Equal to 4 (Head AIS≥4) Assessed to Have Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Imputed Analysis(6 months after injury)
- Subgroup of Participants With Head Abbreviated Injury Scores (AIS) Greater Than or Equal to 2 (Head AIS≥2) Assessed to Have Glasgow Outcome Scale-Extended (GOSE)≤4 at 6 Months: Imputed Analysis(6 months after injury)
- Disability Rating Score (DRS) Categories of Disability(6 months after injury)
- 28 Day Survival(28 days after injury)
- Survival at Hospital Discharge up to 6 Months From Date of Injury(Date of hospital discharge up to 6 months from date of injury)
- Acute Respiratory Distress Syndrome (ARDS)-Free Survival to Day 28(From day of injury to 28 days after injury)
- Worst Multiple Organ Dysfunction Score (MODS) Through Day 28(From day of injury to 28 days after injury)
- Ventilator-free Days Through Day 28(From day of injury to 28 days after injury)
- Days Alive Out of the Intensive Care Unit (ICU) Through Day 28(From day of injury to 28 days after injury)
- Days Alive Out of the Hospital Through Day 28(From day of injury to 28 days after injury)
- Presence of Nosocomial Infections(From day of injury to 28 days after injury)
- Total Fluids in First 24 Hours(First 24 hours from the time dispatch received 911 call)
- Packed Red Blood Cells (PRBC) First 24 Hours(First 24 hours from the time dispatch received 911 call)
- Discharge Disposition(Duration of hospital stay)