CAlcium and VAsopressin Following Injury Early Resuscitation (CAVALIER) Trial (CAVALIER)

June 1, 2026 updated by: Jason Sperry
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1050

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Recruiting
        • University of Arizona
        • Contact:
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • University of Arkansas for Medical Sciences
        • Contact:
    • California
      • San Francisco, California, United States, 94110
        • Recruiting
        • Zuckerberg San Francisco General Hospital and Trauma Center at University of California, San Francisco
        • Contact:
    • Colorado
      • Denver, Colorado, United States, 80204
        • Recruiting
        • Denver Health Medical Center
        • Contact:
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21201
    • Minnesota
      • Minneapolis, Minnesota, United States, 55415
        • Recruiting
        • Hennepin County Medical Center
        • Contact:
    • Missouri
      • Columbia, Missouri, United States, 65202
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Recruiting
        • University of New Mexico
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43213
        • Recruiting
        • Mount Carmel East Hospital
        • Contact:
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University Wexner Medical Center
        • Contact:
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15212
        • Recruiting
        • Allegheny Health Network
        • Contact:
    • Texas
      • Lubbock, Texas, United States, 79430
        • Recruiting
        • Texas Tech University Health Sciences Center
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98104
        • Recruiting
        • University of Washington Harborview Medical Center
        • Contact:
          • Andrew Latimer, MD, FAEMS
          • Phone Number: 206-744-5676
          • Email: alatim@uw.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Drug: Calcium Gluconate
1 gram calcium gluconate provided via intravenous or intraosseous access over approximately 2-5 minutes
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
Drug: saline placebo
saline placebo volume matched to prehospital or in hospital phase
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
Drug: saline placebo
saline placebo volume matched to prehospital or in hospital phase
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.
Drug: Vasopressin
4 unit vasopressin bolus followed by vasopressin infusion at 0.04 U/min for eight hours

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants with 30-day mortality
Time Frame: from randomization to death or 30 days, whichever comes first
all cause mortality within 30 days
from randomization to death or 30 days, whichever comes first

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Blood and blood component transfusion requirements in the initial 6 hours
Time Frame: from randomization to 6 hours
number of units transfused and type
from randomization to 6 hours
Blood and blood component transfusion requirements in the initial 24 hours
Time Frame: from randomization to 24 hours
number of units transfused and type
from randomization to 24 hours
Incidence of Multiple Organ Failure (MOF)
Time Frame: Scores determined daily until up to Day 7 or ICU discharge, whichever comes first
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.
Scores determined daily until up to Day 7 or ICU discharge, whichever comes first
Incidence of nosocomial infection
Time Frame: from randomization to death or 30 days
Utilizing the CDC criteria for diagnosis of hospital acquired pneumonia and blood stream infection
from randomization to death or 30 days
Time to hemostasis
Time Frame: hospital arrival to 4 hours
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"
hospital arrival to 4 hours
Incidence of coagulopathy by thromboelastography (TEG)
Time Frame: within 4 hours of arrival plus or minus 12
TEG date collected only when obtained as part of clinical
within 4 hours of arrival plus or minus 12
Incidence of coagulopathy by thromboelastography (TEG)
Time Frame: within 24 hours of arrival plus or minus 12
TEG date collected only when obtained as part of clinical
within 24 hours of arrival plus or minus 12
ICU free days
Time Frame: From hospital arrival to death or 30 days
number of days the patient is alive and not admitted to ICU subtracted from 30
From hospital arrival to death or 30 days
Hospital free days
Time Frame: From hospital arrival to death or 30 days
number of days the patient is alive and not admitted to hospital subtracted from 30
From hospital arrival to death or 30 days
Number of participants with 6-hour mortality
Time Frame: from randomization to death or 6 hours, whichever comes first
all cause mortality within 6 hours
from randomization to death or 6 hours, whichever comes first
Number of participants with 24-hour mortality
Time Frame: from randomization to death or 24 hours, whichever comes first
all cause mortality within 24 hours
from randomization to death or 24 hours, whichever comes first
Number of participants with In-hospital mortality
Time Frame: In hospital mortality from time of randomization to death or 30 days, whichever comes first
death prior to hospital discharge
In hospital mortality from time of randomization to death or 30 days, whichever comes first
Number of participants with Death from hemorrhage
Time Frame: from randomization to death or 30 days, whichever comes first
Death from hemorrhage adjudicated by the site investigator
from randomization to death or 30 days, whichever comes first
Number of participants with Death from brain injury
Time Frame: from randomization to death or 30 days, whichever comes first
Death from brain injury adjudicated by the site investigator
from randomization to death or 30 days, whichever comes first
Ionized calcium measurements
Time Frame: Measured in the first 60 minutes (+/- 3 hours), when feasible, during early stage resuscitation in emergency department or operating room
Ionized calcium collected as part of clinical care or as research lab
Measured in the first 60 minutes (+/- 3 hours), when feasible, during early stage resuscitation in emergency department or operating room

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jason Sperry

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
United States Department of Defense

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jason Sperry, MD, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 30, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 14, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 14, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 24, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY23040043
  • W81XWH-6-D-0024 (Other Grant/Funding Number: Department of Defense)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified data may be shared with the funding agency as well as other researchers upon request to the Principal Investigator

IPD Sharing Time Frame

Data will become available after publication of the primary manuscript

IPD Sharing Access Criteria

Requests for data will be submitted in writing and reviewed by the Principal Investigator

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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