Clinical trial NCT06820645: Calcium Administration in Life-saving Management During Massive Hemorrhage
Official title: CALM: Calcium Administration in Life-saving Management of Trauma Patients Undergoing Massive Hemorrhage Protocol: a Single Centre Feasibility Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Massive Hemorrhage
Trauma
Hypocalcemia
Keywords: Calcium
Massive Hemorrhage Protocol
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2025-02-11
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This study evaluates the feasibility of conducting a larger study on the impact of treating massive hemorrhage with calcium in trauma patients. Patients undergoing the Massive Hemorrhage Protocol (MHP) will be randomly assigned to receive either calcium gluconate or placebo drug after every 4 packs of units of RBCs received during the MHP.

Detailed description: The treatment of hemorrhage with blood products has been well studied, however very little literature exists on the administration of specific electrolytes such as calcium. Citrate is added to blood products to prevent coagulation by chelating free calcium. This process reduces serum calcium and can lead to hypocalcemia, especially in trauma patients who have altered metabolism, hypovolemia, and receive large quantities of blood products. The majority of trauma patients have hypocalcemia upon arrival at the hospital. Serum hypocalcemia in trauma patients matters because calcium is crucial for bleeding control due to its contributions to platelet function, coagulation, and vasoconstriction. Calcium is also essential for other physiological functions during trauma, such as heart and smooth muscle contractility. It is likely due to these key roles that the literature demonstrates hypocalcemia's association with increased mortality, bleeding, blood transfusion requirements, and coagulopathy.

The primary objective of our proposed trial is to assess the feasibility of conducting an interventional calcium trial on patients undergoing the Massive Hemorrhage Protocol (MHP). Feasibility will be evaluated through the recruitment of patients, adherence to protocol, as well as assessment of any protocol violations that occur during the trial. Secondary objectives of our trial include analyzing the effect calcium supplementation has on patient ionized calcium (iCa) level, total blood product transfused, hemodynamic instability, ICU mortality, and hospital mortality.

The investigators will complete a single-centre, double-blinded randomized control feasibility trial. Both trial arms will receive study drug in accordance with Ontario's Massive Hemorrhage Protocol (MHP). After every 4 units of RBCs, the treatment group will receive 3g of calcium gluconate and the control arm will receive saline placebo. Results will be assessed for feasibility to inform the development of a larger trial.

Eligibility criteria: Inclusion Criteria:

* Adult trauma patients undergoing the MHP at Victoria Hospital, London, Ontario

Exclusion Criteria:

* Under the age of 18
* Pregnant

Primary outcomes:
measure: Feasibility
timeFrame: Through study completion, an estimate of 1 year
Secondary outcomes:
measure: Ionized calcium (iCa)
timeFrame: An estimate of up to 24 hours
measure: Total blood product transfused
timeFrame: Duration of MHP, an average of 1 hour
measure: Hemodynamic instability
timeFrame: Duration of MHP, an average of 1 hour
measure: ICU mortality
timeFrame: 30 days
measure: Hospital mortality
timeFrame: 30 days
Other outcomes:
Locations:
Study officials:
References:
citation: Imamoto T, Sawano M. Effect of ionized calcium level on short-term prognosis in severe multiple trauma patients: a clinical study. Trauma Surg Acute Care Open. 2023 Jun 30;8(1):e001083. doi: 10.1136/tsaco-2022-001083. eCollection 2023.
citation: Morotti A, Charidimou A, Phuah CL, Jessel MJ, Schwab K, Ayres AM, Romero JM, Viswanathan A, Gurol ME, Greenberg SM, Anderson CD, Rosand J, Goldstein JN. Association Between Serum Calcium Level and Extent of Bleeding in Patients With Intracerebral Hemorrhage. JAMA Neurol. 2016 Nov 1;73(11):1285-1290. doi: 10.1001/jamaneurol.2016.2252.
citation: 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.
citation: Vasudeva M, Mathew JK, Groombridge C, Tee JW, Johnny CS, Maini A, Fitzgerald MC. Hypocalcemia in trauma patients: A systematic review. J Trauma Acute Care Surg. 2021 Feb 1;90(2):396-402. doi: 10.1097/TA.0000000000003027.
citation: Vincent JL, Bredas P, Jankowski S, Kahn RJ. Correction of hypocalcaemia in the critically ill: what is the haemodynamic benefit? Intensive Care Med. 1995 Oct;21(10):838-41. doi: 10.1007/BF01700968.
citation: 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.
citation: Bell KT, Salmon CM, Purdy BA, Canfield SG. EVALUATION OF TRANEXAMIC ACID AND CALCIUM CHLORIDE IN MAJOR TRAUMAS IN A PREHOSPITAL SETTING: A NARRATIVE REVIEW. Shock. 2023 Sep 1;60(3):325-332. doi: 10.1097/SHK.0000000000002177. Epub 2023 Jul 12.
citation: Torres CM, Kenzik KM, Saillant NN, Scantling DR, Sanchez SE, Brahmbhatt TS, Dechert TA, Sakran JV. Timing to First Whole Blood Transfusion and Survival Following Severe Hemorrhage in Trauma Patients. JAMA Surg. 2024 Apr 1;159(4):374-381. doi: 10.1001/jamasurg.2023.7178.
citation: Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma. 2007 Oct;63(4):805-13. doi: 10.1097/TA.0b013e3181271ba3.
citation: Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, del Junco DJ, Brasel KJ, Bulger EM, Callcut RA, Cohen MJ, Cotton BA, Fabian TC, Inaba K, Kerby JD, Muskat P, O'Keeffe T, Rizoli S, Robinson BR, Scalea TM, Schreiber MA, Stein DM, Weinberg JA, Callum JL, Hess JR, Matijevic N, Miller CN, Pittet JF, Hoyt DB, Pearson GD, Leroux B, van Belle G; PROPPR Study Group. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015 Feb 3;313(5):471-82. doi: 10.1001/jama.2015.12.
citation: Saviano A, Perotti C, Zanza C, Longhitano Y, Ojetti V, Franceschi F, Bellou A, Piccioni A, Jannelli E, Ceresa IF, Savioli G. Blood Transfusion for Major Trauma in Emergency Department. Diagnostics (Basel). 2024 Mar 27;14(7):708. doi: 10.3390/diagnostics14070708.