CAlcium and VAsopressin Following Injury Early Resuscitation (CAVALIER) Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Jason Sperry
- 入组人数
- 1,050
- 试验地点
- 23
- 主要终点
- Number of participants with 30-day mortality
研究概览
简要总结
The CAlcium and VAsopressin following Injury Early Resuscitation (CAVALIER) Trial is a proposed 4 year, double-blind, mutli-center, prehospital and early in hospital phase randomized trial designed to determine the efficacy and safety of prehospital calcium and early in hospital vasopressin in patients at risk of hemorrhagic shock.
详细描述
Resuscitation strategies for the acutely injured patient in hemorrhagic shock have evolved. Patients benefit from receiving less crystalloid in favor of blood transfusions with balanced ratios of plasma and platelets or whole blood resuscitation. These resuscitation practices are termed Damage Control Resuscitation and have been incorporated into resuscitation protocols in Level I trauma centers across the country. Damage Control Resuscitation represents standard practice for military and civilian trauma. Despite these changes, deaths from traumatic hemorrhage continue to occur in the first hours following trauma center arrival, underscoring the importance of early, novel interventions.
Hypocalcemia following traumatic injury is exceedingly common following severe traumatic injury in patients at risk of hemorrhagic shock. During hemorrhagic shock resuscitation, pathways reliant upon calcium such as platelet function, intrinsic and extrinsic hemostasis, and cardiac contractility are disrupted. Citrate containing transfusion products are known to further reduce calcium levels through chelation during trauma resuscitation. Hypocalcemia has consistently been shown to be independently associated with the risk of large volume blood transfusion and mortality. Current management practices include calcium replacement during the in hospital phase of care in patients receiving blood products. Early calcium replacement in patients at risk of hemorrhage and hypocalcemia may mitigate coagulopathy, maintain hemostasis, improve hemodynamics and outcomes, and may reduce complications attributable to hemorrhagic shock.
Arginine vasopressin is a physiologic hormone released by the posterior pituitary in response to hypotension and is commonly used as a vasopressor for critically ill patients for the treatment of hypotension due to multiple causes including sepsis. Prolonged hemorrhagic shock has the potential to alter systemic vasomotor tone which can progress to refractory/recalcitrant hypotension. Patients receiving resuscitation for hemorrhage are at risk of vasopressin deficiency. Vasopressin may improve hemostasis by enhancing platelet function and augmenting clot formation. Vasopressin infusion soon after injury in patients in hemorrhagic shock has been demonstrated to be safe and result in a reduction in blood transfusion requirements and a lower incidence of deep venous thrombosis.
Whole blood, red cells, and blood components are a precious and limited resource. Trauma resuscitation adjuncts such as early calcium and vasopressin may provide benefit when transfusion products are limited and may provide additional benefit even when transfusion capabilities remain robust. Due to their action on coagulation and hemodynamic cascades in the injured patient, these resuscitation adjuncts have the potential to interact and provide additive benefit to the injured patient. However, safety and efficacy of prehospital calcium and early in hospital vasopressin remain inadequately characterized. Enrolled patients may participate in the prehospital phase (calcium), in-hospital phase (vasopressin), or both. The aims of the CAlcium and VAsopressin following Injury Early Resuscitation (CAVALIER) trial are to determine the efficacy and safety of prehospital calcium supplementation and early in hospital vasopressin infusion as compared to standard care resuscitation in patients at risk of hemorrhagic shock and to appropriately characterize any additive effect of both resuscitation adjunct interventions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Prehospital Phase:
- •Injured patients at risk of hemorrhagic shock being transported from scene or referral hospital to a participating CAVALIER trial site who meet the following criteria:
- •1A. Systolic blood pressure ≤ 90mmHg and tachycardia (HR ≥ 108) at scene, at outside hospital, or during anticipated transport to a participating CAVALIER trial site
- •1B. Systolic blood pressure ≤ 70mmHg at scene, at outside hospital, or during anticipated transport to a participating CAVALIER trial site
- •Early In-Hospital Phase:
- •Injured patients at a participating CAVALIER trial site at risk of hemorrhagic shock who meet the following criteria:
- •1A. Systolic blood pressure ≤ 90mmHg and tachycardia (HR ≥ 108) at scene, at outside hospital, during transport, or in emergency department of a participating CAVALIER trial site
- •1B. Systolic blood pressure ≤ 70mmHg at scene, at outside hospital, during transport, or in emergency department of a participating CAVALIER trial site
- •2.Blood/blood component transfusion initiated in prehospital setting or deemed clinically indicated within 60 minutes of arrival at the enrolling trauma center
- •Clinical team deems Operating Room for major hemorrhage control procedure (e.g., laparotomy, thoracotomy, vascular exploration or extremity amputation) indicated within 60 minutes of arrival at the enrolling trauma center
- •4. Anticipated admission to intensive care unit (ICU)
排除标准
- •Prehospital Phase
- •Wearing NO CAVALIER opt-out bracelet
- •Age > 90 or < 18 years of age
- •Isolated fall from standing injury mechanism
- •Known prisoner
- •Known pregnancy
- •Traumatic arrest with > 5 minutes of CPR without return of vital signs
- •Brain matter exposed or penetrating brain injury
- •Isolated drowning or hanging victims
- •Objection to study voiced by subject or family member at the scene or at the trauma center
- •Inability to obtain IV/IO access
- •Early In-Hospital Phase:
- •Wearing NO CAVALIER opt-out bracelet
- •Age > 90 or < 18 years of age
- •Isolated fall from standing injury mechanism
- •Known prisoner
- •Known pregnancy
- •Traumatic arrest with > 5 minutes of CPR without return of vital signs
- •Brain matter exposed or penetrating brain injury
- •Isolated drowning or hanging victims
- •Objection to study voiced by subject or family member at the scene or at the trauma center
- •Inability to obtain IV access
研究组 & 干预措施
Early In-Hospital Control Arm
volume matched saline bolus followed by volume matched normal saline placebo infusion for eight hours initiated within approximately two hours of enrollment
干预措施: saline placebo (Drug)
Prehospital Control Arm
Identical volume saline placebo to prehospital intervention arm provided via intravenous or intraosseous access over approximately 2-5 minutes, initiated prior to trauma bay arrival and infused to completion following arrival if needed
干预措施: saline placebo (Drug)
Prehospital Intervention Arm
1 gram calcium gluconate provided via intravenous or intraosseous access over approximately 2-5 minutes, initiated prior to trauma bay arrival and infused to completion following arrival if needed
干预措施: Calcium Gluconate (Drug)
Early In-Hospital Intervention Arm
4-unit vasopressin bolus followed by a vasopressin infusion at 0.04 U/min for 8 hours. Administration of the bolus will be initiated as soon as feasible and within approximately 2 hours of enrollment. The infusion will be initiated within approximately 30 minutes of the bolus.
干预措施: Vasopressin (Drug)
结局指标
主要结局
Number of participants with 30-day mortality
时间窗: from randomization to death or 30 days, whichever comes first
all cause mortality within 30 days
次要结局
- Time to hemostasis(hospital arrival to 4 hours)
- Incidence of coagulopathy by thromboelastography (TEG)(within 24 hours of arrival plus or minus 12)
- ICU free days(From hospital arrival to death or 30 days)
- Blood and blood component transfusion requirements in the initial 24 hours(from randomization to 24 hours)
- Incidence of Multiple Organ Failure (MOF)(Scores determined daily until up to Day 7 or ICU discharge, whichever comes first)
- Incidence of nosocomial infection(from randomization to death or 30 days)
- Number of participants with 6-hour mortality(from randomization to death or 6 hours, whichever comes first)
- Number of participants with 24-hour mortality(from randomization to death or 24 hours, whichever comes first)
- Number of participants with In-hospital mortality(In hospital mortality from time of randomization to death or 30 days, whichever comes first)
- Number of participants with Death from hemorrhage(from randomization to death or 30 days, whichever comes first)
- Number of participants with Death from brain injury(from randomization to death or 30 days, whichever comes first)
- Blood and blood component transfusion requirements in the initial 6 hours(from randomization to 6 hours)
- Hospital free days(From hospital arrival to death or 30 days)
- Ionized calcium measurements(Measured in the first 60 minutes (+/- 3 hours), when feasible, during early stage resuscitation in emergency department or operating room)
- Incidence of coagulopathy by thromboelastography (TEG)(within 4 hours of arrival plus or minus 12)