Empiric Calcium in Massive Transfusion

• ClinicalTrials.gov Identifier: NCT05953376
• Recruitment Status: Not yet recruiting
• First Posted: July 20, 2023
• Last Update Posted: April 8, 2024
• Sponsor: University of California, Irvine
• Information provided by (Responsible Party): Jeffrey Nahmias, MD, University of California, Irvine

Study Description

Brief Summary:

Calcium helps blood to clot and thereby stop bleeding. Trauma patients who experience large volume blood loss often require blood transfusions and bleeding is the most common cause of death. The purpose of this study is to see if giving intravenous calcium immediately to patients who require large volume blood transfusion will decrease transfusion requirements, vasopressor use and mortality in bleeding trauma patients.

Condition or disease	Intervention/treatment	Phase
Hemorrhage; Trauma; Hypocalcemia; Shock, Hemorrhagic	Drug: Calcium Gluconate	Phase 3

Detailed Description:

Advancements in the area of transfusion and blood product administration have occurred with the use of viscoelastic assays and whole blood. However, as we resuscitate trauma patients with blood products, hypocalcemia is an inadvertent side-effect. Citrate within stored blood binds calcium, causing patients to have hypocalcemia. In addition, outside of transfusion related hypocalcemia there is an independent trauma/inflammation related mechanism for hypocalcemia in the trauma patient. Furthermore, Calcium is a critical component of the coagulation cascade, and therefore a highly important component of hemostatic resuscitation. Hall et al found that patients receiving 13 or more units of PRBCs had a much higher prevalence of severe hypocalcemia and at least one ionized calcium <1.0mmol/L. Kronstedt el al reported an association between hypocalcemia and mortality in trauma patients receiving massive transfusion. Despite evidence that hypocalcemia occurs with transfusion, and evidence that hypocalcemia in patients with hemorrhagic shock may be associated with increased mortality, there are no randomized controlled trials evaluating the administration of calcium in trauma resuscitation. Currently, the Joint Trauma System revised guidelines for damage control resuscitation from 2019 recommend administering 1g of calcium after the first unit of blood transfusion, and an additional 1g after no more than 4 units of blood administration. However, these recommendations are based on small cohort studies or retrospective studies. The purpose of this study is to evaluate the efficacy of early empiric intravenous calcium administration on transfusion requirements, vasopressor use and mortality in hemorrhaging trauma patients with initiation of a massive transfusion.

All trauma patients in which massive transfusion is initiated within 6 hours of arrival will be enrolled. Two study arms will be created, one will receive 2g IV calcium with the initial transfusion and the other will only receive calcium supplementation based on routine ionized calcium levels and/or physician discretion. All critical trauma activations will get a baseline ionized calcium as part of their initial labs.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Empiric Calcium Versus Lab Based Treatment in Massive Transfusion Trauma Patients: A Feasibility Randomized Controlled Trial
• Estimated Study Start Date: January 2025
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Empiric calcium administration; Patients in this arm will receive 2g IV calcium with the initial transfusion	Drug: Calcium Gluconate; There will be 2 study arms, one will receive 2g IV calcium with the initial transfusion and the other will only receive calcium supplementation based on routine ionized calcium levels and/or physician discretion.; Other Name: Calcium
No Intervention: No empiric calcium administration; Patients in this arm will only receive calcium supplementation based on routine ionized calcium levels and/or physician discretion

Outcome Measures

Primary Outcome Measures :

1. Transfusion requirements [ Time Frame: During first 24 hours of resuscitation ]
   Number of packed red blood cells, whole blood, fresh frozen plasma, platelets and cryo units given

Secondary Outcome Measures :

1. Mortality [ Time Frame: 30-day mortality ]
   30-day mortality or until discharge (whichever is longer)
2. Vasopressor use [ Time Frame: During first 24 hours of resuscitation ]
   Amount of vasopressor used within the first 24 hours measured in levophed equivalents

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Trauma patients receiving massive transfusion protocol

Exclusion Criteria:

• Pregnancy
• Prisoners
• Known history of hypercalcemia
• Active hyperparathyroidism
• Hemophilia

Contacts and Locations

Contacts

Contact: Jeffry Nahmias, MD; 714-456-5890; jnahmias@hs.uci.edu

Contact: Mallory Jebbia, MD; 714-456-5860; mjebbia@hs.uci.edu

Sponsors and Collaborators

University of California, Irvine

Investigators

• Principal Investigator: Jeffry Nahmias, MD; University of California, Irvine

More Information

Publications:

Hall C, Nagengast AK, Knapp C, Behrens B, Dewey EN, Goodman A, Bommiasamy A, Schreiber M. Massive transfusions and severe hypocalcemia: An opportunity for monitoring and supplementation guidelines. Transfusion. 2021 Jul;61 Suppl 1:S188-S194. doi: 10.1111/trf.16496.

Giancarelli A, Birrer KL, Alban RF, Hobbs BP, Liu-DeRyke X. Hypocalcemia in trauma patients receiving massive transfusion. J Surg Res. 2016 May 1;202(1):182-7. doi: 10.1016/j.jss.2015.12.036. Epub 2015 Dec 30.

Kronstedt S, Roberts N, Ditzel R, Elder J, Steen A, Thompson K, Anderson J, Siegler J. Hypocalcemia as a predictor of mortality and transfusion. A scoping review of hypocalcemia in trauma and hemostatic resuscitation. Transfusion. 2022 Aug;62 Suppl 1(Suppl 1):S158-S166. doi: 10.1111/trf.16965. Epub 2022 Jun 24.

Vettorello M, Altomare M, Spota A, Cioffi SPB, Rossmann M, Mingoli A, Chiara O, Cimbanassi S. Early Hypocalcemia in Severe Trauma: An Independent Risk Factor for Coagulopathy and Massive Transfusion. J Pers Med. 2022 Dec 28;13(1):63. doi: 10.3390/jpm13010063.

• Responsible Party: Jeffrey Nahmias, MD, Associate Professor of Surgery, University of California, Irvine
• ClinicalTrials.gov Identifier: NCT05953376
• Other Study ID Numbers: 3115
• First Posted: July 20, 2023
• Last Update Posted: April 8, 2024
• Last Verified: April 2024

• 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.: Yes

Additional relevant MeSH terms:

Hypocalcemia; Hemorrhage; Shock, Hemorrhagic; Pathologic Processes; Calcium Metabolism Disorders; Metabolic Diseases; Water-Electrolyte Imbalance; Shock; Calcium, Dietary; Calcium; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Bone Density Conservation Agents