CAlcium and VAsopressin Following Injury Early Resuscitation (CAVALIER) Trial
Purpose
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.
Conditions
- Trauma
- Hemorrhage
Eligibility
- Eligible Ages
- Between 18 Years and 90 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
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 OR 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 OR 1B. Systolic blood pressure ≤ 70mmHg at scene, at outside hospital, during transport, or in emergency department of a participating CAVALIER trial site AND 2.Blood/blood component transfusion initiated in prehospital setting or deemed clinically indicated within 60 minutes of arrival at the enrolling trauma center AND 3. 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 AND 4. Anticipated admission to intensive care unit (ICU)
Exclusion Criteria
Prehospital Phase 1. Wearing NO CAVALIER opt-out bracelet 2. Age > 90 or < 18 years of age 3. Isolated fall from standing injury mechanism 4. Known prisoner 5. Known pregnancy 6. Traumatic arrest with > 5 minutes of CPR without return of vital signs 7. Brain matter exposed or penetrating brain injury 8. Isolated drowning or hanging victims 9. Objection to study voiced by subject or family member at the scene or at the trauma center 10. Inability to obtain IV/IO access Early In-Hospital Phase: 1. Wearing NO CAVALIER opt-out bracelet 2. Age > 90 or < 18 years of age 3. Isolated fall from standing injury mechanism 4. Known prisoner 5. Known pregnancy 6. Traumatic arrest with > 5 minutes of CPR without return of vital signs 7. Brain matter exposed or penetrating brain injury 8. Isolated drowning or hanging victims 9. Objection to study voiced by subject or family member at the scene or at the trauma center 10. Inability to obtain IV access
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- In-Hospital phase: permuted block design
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 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 |
|
|
Placebo Comparator 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 |
|
|
Experimental 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. |
|
|
Placebo Comparator 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 |
|
Recruiting Locations
Tucson 5318313, Arizona 5551752 85724
San Francisco 5391959, California 5332921 94110
Denver 5419384, Colorado 5417618 80204
Miami 4164138, Florida 4155751 33136
Minneapolis 5037649, Minnesota 5037779 55415
Albuquerque 5454711, New Mexico 5481136 87131
Pittsburgh 5206379, Pennsylvania 6254927 15212
Pittsburgh 5206379, Pennsylvania 6254927 15213
Seattle 5809844, Washington 5815135 98104
More Details
- NCT ID
- NCT05958342
- Status
- Recruiting
- Sponsor
- Jason Sperry
Detailed Description
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.