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

NCT ID: NCT06070350

Last Updated: 2025-03-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-01

Study Completion Date

2028-10-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hemorrhagic Shock Trauma Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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 Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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Group 1 (LTOWB+TXA)

Concurrent administration of LTOWB and TXA

Group Type OTHER

Low Titer Group O Whole Blood (LTOWB)

Intervention Type BIOLOGICAL

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.

Tranexamic Acid (TXA)

Intervention Type DRUG

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).

Group 2 (LTOWB+Placebo)

Concurrent administration of LTOWB and Placebo

Group Type OTHER

Low Titer Group O Whole Blood (LTOWB)

Intervention Type BIOLOGICAL

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.

Placebo

Intervention Type DRUG

Placebo will be provided to the research pharmacy at each of the clinical sites

Group 3 (CT+TXA)

Concurrent administration of CT and TXA

Group Type OTHER

Tranexamic Acid (TXA)

Intervention Type DRUG

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).

Component Therapy (CT)

Intervention Type BIOLOGICAL

Component Therapy (CT) will be RBCs, plasma and platelet units in a 1:1:1 unit ratio. This will be given with Placebo

Group 4 (CT+Placebo)

Concurrent administration of CT and Placebo

Group Type OTHER

Placebo

Intervention Type DRUG

Placebo will be provided to the research pharmacy at each of the clinical sites

Component Therapy (CT)

Intervention Type BIOLOGICAL

Component Therapy (CT) will be RBCs, plasma and platelet units in a 1:1:1 unit ratio. This will be given with Placebo

Interventions

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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.

Intervention Type BIOLOGICAL

Placebo

Placebo will be provided to the research pharmacy at each of the clinical sites

Intervention Type 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).

Intervention Type DRUG

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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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).

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


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
Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biomedical Advanced Research and Development Authority

FED

Sponsor Role collaborator

Philip Spinella

OTHER

Sponsor Role lead

Responsible Party

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Philip Spinella

Professor of Surgery and Critical Care Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Philip C Spinella, MD

Role: PRINCIPAL_INVESTIGATOR

Univesrity of Pittsburgh

Locations

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University of Arizona

Tucson, Arizona, United States

Site Status RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status RECRUITING

University of California Davis

Sacramento, California, United States

Site Status RECRUITING

Children's National Hospital

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Emory University-Arthur M. Blank Hospital

Atlanta, Georgia, United States

Site Status RECRUITING

Emory University-Scottish Rite Hospital

Atlanta, Georgia, United States

Site Status RECRUITING

Tulane School of Medicine

New Orleans, Louisiana, United States

Site Status RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status RECRUITING

Washington University of St. Louis

St Louis, Missouri, United States

Site Status RECRUITING

University of New Mexico

Albuquerque, New Mexico, United States

Site Status RECRUITING

Wake Forest University Health Sciences

Wake Forest, North Carolina, United States

Site Status RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status RECRUITING

Oregon Health and Science University

Portland, Oregon, United States

Site Status RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

LeBonheur Children's Hospital

Memphis, Tennessee, United States

Site Status RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status NOT_YET_RECRUITING

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Baylor College of Medicine

Houston, Texas, United States

Site Status RECRUITING

Children's Memorial Hermann Hospital

Houston, Texas, United States

Site Status RECRUITING

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status RECRUITING

University of Washington Harborview

Seattle, Washington, United States

Site Status RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jane Luce

Role: CONTACT

412-383-7853

Facility Contacts

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Maxson

Role: primary

References

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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.

Reference Type DERIVED
PMID: 39898869 (View on PubMed)

Other Identifiers

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MATIC-002

Identifier Type: -

Identifier Source: org_study_id

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