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.

CAlcium and VAsopressin Following Injury Early Resuscitation (CAVALIER) Trial

Trauma

Hemorrhage

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.

Calcium Gluconate

Vasopressin

saline placebo

Professor

Death from hemorrhage adjudicated by the site investigator

Death from brain injury adjudicated by the site investigator

Evaluated via the Denver Post injury Multiple Organ Failure Score, characterized as an incidence rate (percentage) and as MOF free days. Patients never admitted to ICU or with length of stay less than 48 hours will have a score of 0. A summary Denver score of >3 will be classified as MOF.

Utilizing the CDC criteria for diagnosis of hospital acquired pneumonia and blood stream infection

Determined by ability to reach nadir transfusion requirement of 1 unit of red blood cells in a 60 minute period in the first 4 hours following arrival. In the absence of ability to obtain hemostasis within the first 4 hours, the patient will be designated "non-hemostasis"

TEG date collected only when obtained as part of clinical

number of days the patient is alive and not admitted to ICU subtracted from 30

number of days the patient is alive and not admitted to hospital subtracted from 30

1 gram calcium gluconate provided intravenously over approximately 5 minutes, initiated prior to trauma bay arrival and infused to completion following arrival if needed

Identical volume saline placebo to prehospital intervention arm provided intravenously over approximately 5 minutes, initiated prior to trauma bay arrival and infused to completion following arrival if needed

4 unit vasopressin bolus followed by a vasopressin infusion at 0.04 U/min for eight hours, initiated within approximately two hours of hospital arrival

volume matched saline bolus followed by volume matched normal saline placebo infusion for eight hours initiated within approximately two hours of arrival

CAlcium and VAsopressin Following Injury Early Resuscitation (CAVALIER) Trial

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status