Massive Transfusion in Children-2: A Trial Examining Life Threatening Hemorrhage in Children (MATIC-2)

Massive Transfusion in Children: a Platform RCT of Whole Blood Compared to Component Therapy and Tranexamic Acid to Placebo in Life-threatening Traumatic Bleeding

The MATIC-2 is a multicenter clinical trial enrolling children who are less than 18 years of age with hemorrhagic shock potentially needing significant blood transfusion.

The primary objective of the clinical trial is to determine the effectiveness of Low Titer Group O Whole Blood (LTOWB) compared to component therapy (CT), and Tranexamic Acid (TXA) compared to placebo in decreasing 24-hour all-cause mortality in children with traumatic life threatening hemorrhage.

Study Overview

• Status: Recruiting
• Conditions: Hemorrhagic Shock; Trauma Injury
• Intervention / Treatment: Biological: Low Titer Group O Whole Blood (LTOWB); Biological: Component Therapy (CT); Drug: Placebo; Drug: Tranexamic Acid (TXA)

Detailed Description

The MATIC-2 trial is a Bayesian, randomized, multicenter, adaptive platform phase III trial. The trial will include injured children with hemorrhagic shock anticipated to require massive blood transfusion, who will be randomized to receive either LTOWB or CT and Tranexamic Acid or placebo.

The study investigators hypothesize that the use of LTOWB is non-inferior and/or superior for 24-hour mortality and that LTOWB does not increase the risk of adverse events or outcomes, such as thrombotic events, compared to CT.

The investigators also hypothesize that the use of TXA is superior for 24-hour mortality and does not increase the risk of adverse events or outcomes, such as thrombotic events, compared to placebo.

Objectives:

The primary objectives are to:

1. Determine the effectiveness of LTOWB to reduce all-cause 24-hour mortality compared to CT in children with traumatic life-threatening hemorrhage.
2. Determine the effectiveness of TXA to reduce all-cause 24-hour mortality compared to placebo in children with traumatic life-threatening hemorrhage.

Secondary objectives are to determine the effectiveness and safety of LTOWB and TXA to improve secondary and exploratory outcomes (or endpoints) in children with traumatic life-threatening hemorrhage.

Safety objectives are to determine the effect of LTOWB and TXA on safety related outcomes/endpoints. The safety outcomes include:

1. Acute kidney injury
2. Acute respiratory distress syndrome
3. Arrhythmia
4. Abdominal compartment syndrome
5. Bleeding after hemostasis requiring intervention
6. Myocardial infarction
7. Pneumonia
8. Sepsis
9. Stroke
10. Seizure
11. Thrombotic events (arterial or venous)
12. Urinary Tract Infection
13. Alloimmunization in Rh negative female recipients of Rh+ LTOWB or RBC's
14. Organ failure (as determined by PELOD-2 score)

Mechanistic Objectives are to:

1. Define trauma induced coagulopathy (TIC) according to measures of shock, hemostasis, and endothelial and immune function.
2. To determine if measures of shock, endothelial, immune, and hemostasis function upon admission (TIC endotype) predicts which hemostatic resuscitation therapies or combinations of therapies (LTOWB, CT, LTOWB + TXA, CT+TXA) for each study group improves outcomes without increasing the risk of adverse events.
3. To determine the mechanisms of how hemostatic resuscitation therapies or combinations of therapies (LTOWB, CT, LTOWB + TXA, CT+TXA) improve TIC endotypes and outcomes.

Pharmacokinetic objectives are to evaluate the PK and PD properties of TXA in a population of children with life-threatening traumatic bleeding.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Thomas Byers; Phone Number: 412-383-2340; Email: tdb33@pitt.edu

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 84719
      • Recruiting
      • University of Arizona
      • Principal Investigator: Louis Magnotti, MD
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Recruiting
      • Arkansas Children's Hospital
      • Contact: Maxson
      • Principal Investigator: Todd Maxson, MD
  • California
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California Davis
      • Principal Investigator: Daniel Nishijima, MD
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • Children's National Hospital
      • Principal Investigator: Randall Burd, MD
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Emory University-Arthur M. Blank Hospital
      • Principal Investigator: Ruth Hwu, MD
    • Atlanta, Georgia, United States, 30342
      • Terminated
      • Emory University-Scottish Rite Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Withdrawn
      • Tulane School of Medicine
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Recruiting
      • University of Mississippi Medical Center
      • Principal Investigator: Matthew Kutcher, MD
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University of St. Louis
      • Principal Investigator: Lindsay Clukies, MD
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Recruiting
      • University of New Mexico
      • Principal Investigator: Sarah Moore, MD
  • North Carolina
    • Wake Forest, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest University Health Sciences
      • Principal Investigator: Lucas Neff, MD
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
      • Principal Investigator: Julie Leonard, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
      • Principal Investigator: Trisha Wong, MD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • Children's Hospital of Pittsburgh of UPMC
      • Principal Investigator: Ward Richardson, MD
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Recruiting
      • LeBonheur Children's Hospital
      • Principal Investigator: Regan Williams, MD
    • Nashville, Tennessee, United States, 37232
      • Not yet recruiting
      • Vanderbilt University Medical Center
      • Principal Investigator: Harold Lovvorn, MD
  • Texas
    • Dallas, Texas, United States, 75390
      • Terminated
      • The University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Principal Investigator: Adam Vogel, MD
    • Houston, Texas, United States, 77030
      • Recruiting
      • Children's Memorial Hermann Hospital
      • Principal Investigator: Charles Cox, MD
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • University of Texas Health Science Center at San Antonio
      • Principal Investigator: Susannah Nicholson, MD
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • Primary Children's Hospital
      • Principal Investigator: Katie Russell, MD
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington Harborview
      • Principal Investigator: Bryce Robinson, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin
      • Principal Investigator: Katherine Flynn-O'Brien, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

General Inclusion Criteria:

1. Children, defined as less than estimated18 years of age with traumatic injury
2. MTP activation for confirmed or suspected active life-threatening traumatic bleeding

AND

Confirmed or suspected active life-threatening traumatic bleeding with at least 2 of 3 of the following criteria:

1. Hypotension for age (< 5% tile)
2. Tachycardia for age (>95th % tile)
3. Traumatic injury with exam findings consistent with severe bleeding (e.g., penetrating injury, hemothorax, distended abdomen with bruising, amputation of limb).

General Exclusion Criteria:

1. Patient with devastating traumatic brain injury not expected to survive due to magnitude of injury (example: Transhemispheric gunshot wound with signs of herniation, GCS score of 3 with fixed and dilated pupils)
2. MTP activated but no blood products given
3. Patients who required an ED thoracotomy or received more than 5 consecutive minutes of cardiopulmonary resuscitation (prior to receiving randomized blood products)
4. Patients who are known or suspected to be pregnant on clinical examination
5. Known prisoners as defined in protocol
6. Known ward of the state
7. Isolated hanging, drowning or burns
8. Previous enrollment in MATIC-2
9. Prior study opt-out with bracelet

Exclusion Criteria for the TXA/Placebo Domain

1. Prehospital or pre-enrollment use of TXA
2. Greater than 3 hours since time of injury
3. History of seizure after the injury event
4. Known allergy or hypersensitivity reaction to TXA

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group 2 (LTOWB+Placebo); Concurrent administration of LTOWB and Placebo	Biological: Low Titer Group O Whole Blood (LTOWB); LTOWB is whole blood from group O donors with low titer (<200) anti-A and anti-B antibodies. Up to 8 units of LTOWB will be allowed unless local clinical practice allows for a higher maximum dose.; Drug: Placebo; Placebo will be provided to the research pharmacy at each of the clinical sites
Other: Group 4 (CT+Placebo); Concurrent administration of CT and Placebo	Biological: Component Therapy (CT); Component Therapy (CT) will be RBCs, plasma and platelet units in a 1:1:1 unit ratio. This will be given with Placebo; Drug: Placebo; Placebo will be provided to the research pharmacy at each of the clinical sites
Other: Group 1 (LTOWB+TXA); Concurrent administration of LTOWB and TXA	Biological: Low Titer Group O Whole Blood (LTOWB); LTOWB is whole blood from group O donors with low titer (<200) anti-A and anti-B antibodies. Up to 8 units of LTOWB will be allowed unless local clinical practice allows for a higher maximum dose.; Drug: Tranexamic Acid (TXA); TXA is a synthetic lysine analog that competitively inhibit activation of plasminogen, thereby decreasing the conversion of plasminogen to plasmin, preventing degradation of fibrin's matrix structure. Dose is 25mg/kg IV or IO (maximum 2 grams).
Other: Group 3 (CT+TXA); Concurrent administration of CT and TXA	Biological: Component Therapy (CT); Component Therapy (CT) will be RBCs, plasma and platelet units in a 1:1:1 unit ratio. This will be given with Placebo; Drug: Tranexamic Acid (TXA); TXA is a synthetic lysine analog that competitively inhibit activation of plasminogen, thereby decreasing the conversion of plasminogen to plasmin, preventing degradation of fibrin's matrix structure. Dose is 25mg/kg IV or IO (maximum 2 grams).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
24 hours all cause mortality	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-hour, 72-hour and 28-day survival	Cumulative survival over time through 28 days post-enrollment: includes 6-hour, 72-hour and 28-day survival.	6, 72 hours and 28 days
24 hours total blood product transfusion volumes	Total blood product transfusion in 24 hours after enrollment.	24 hours

Collaborators and Investigators

• Sponsor: Philip Spinella
• Collaborators: Biomedical Advanced Research and Development Authority
• Investigators: Principal Investigator: Philip C Spinella, MD, Univesrity of Pittsburgh

Publications and helpful links

General Publications

• Petersen EM, Fisher AD, April MD, Yazer MH, Braverman MA, Borgman MA, Schauer SG. The effect of the proportion of low-titer O whole blood for resuscitation in pediatric trauma patients on 6-, 12- and 24-hour survival. J Trauma Acute Care Surg. 2025 Apr 1;98(4):587-592. doi: 10.1097/TA.0000000000004564. Epub 2025 Feb 3.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: September 27, 2023
• First Submitted That Met QC Criteria: September 29, 2023
• First Posted (Actual): October 6, 2023

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 20, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Children; Pediatrics; Transfusion
• Additional Relevant MeSH Terms: Wounds and Injuries; Pathologic Processes; Hemorrhage; Shock; Pathological Conditions, Signs and Symptoms; Accidental Injuries; Shock, Hemorrhagic; Organic Chemicals; Carboxylic Acids; Acids, Carbocyclic; Cyclohexanecarboxylic Acids; Tranexamic Acid
• Other Study ID Numbers: MATIC-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared 5 years after the trial has been published. The trial database will be shared to those who request the data and agree to collaborate with the principal investigators for the additional analyses.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

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