Trials Today

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

Purpose

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.

Conditions

Hemorrhagic Shock
Trauma Injury

Eligibility

Eligible Ages: Under 17 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

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

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 Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: MATIC-2 is a Bayesian, randomized, multicenter, adaptive platform phase III trial to examine the effectiveness and safety of LTOWB versus CT and TXA vs placebo in 1000 children at minimum 20 US high volume academic pediatric trauma centers. Mechanisms of Trauma induced Coagulopathy (TIC) and resuscitation effects will also be investigated. The trial will stratify pediatric trauma centers based on their reported Massive Transfusion Protocol (MTP) volume and then randomize them into four treatment combinations. After an initial enrollment phase, treatment sites will cross over to ensure that all treatments are tested across every site, eliminating biases by the time of the first interim analysis.
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The University of Pittsburgh Medical Center Investigational Research Pharmacy will provide each site the placebo and TXA. The research pharmacy at each site will draw the dose syringes. They will be blinded with a label indicating either drug A or B, and the pharmacy will log which patients received TXA or placebo, with all drugs labeled as investigational products.

Arm Groups

Arm	Description	Assigned Intervention
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 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 3 (CT+TXA)	Concurrent administration of CT and TXA	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). 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
Other Group 4 (CT+Placebo)	Concurrent administration of CT and Placebo	Drug: Placebo Placebo will be provided to the research pharmacy at each of the clinical sites 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

Recruiting Locations

University of Arizona
Tucson, Arizona 84719

Arkansas Children's Hospital
Little Rock, Arkansas 72202

Contact:
Maxson

University of California Davis
Sacramento, California 95817

Children's National Hospital
Washington D.C., District of Columbia 20010

Emory University-Arthur M. Blank Hospital
Atlanta, Georgia 30329

Emory University-Scottish Rite Hospital
Atlanta, Georgia 30342

Tulane School of Medicine
New Orleans, Louisiana 70118

University of Mississippi Medical Center
Jackson, Mississippi 39216

Washington University of St. Louis
St Louis, Missouri 63110

University of New Mexico
Albuquerque, New Mexico 87131

Wake Forest University Health Sciences
Wake Forest, North Carolina 27157

Nationwide Children's Hospital
Columbus, Ohio 43205

Oregon Health and Science University
Portland, Oregon 97239

Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania 15224

LeBonheur Children's Hospital
Memphis, Tennessee 38103

The University of Texas Southwestern Medical Center
Dallas, Texas 75390

Baylor College of Medicine
Houston, Texas 77030

Children's Memorial Hermann Hospital
Houston, Texas 77030

University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229

Primary Children's Hospital
Salt Lake City, Utah 84112

University of Washington Harborview
Seattle, Washington 98195

Medical College of Wisconsin
Milwaukee, Wisconsin 53226

More Details

NCT ID: NCT06070350
Status: Recruiting
Sponsor: Philip Spinella

Study Contact

Jane Luce
412-383-7853
jane.luce@pitt.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.