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

Primary Purpose

Hemorrhagic Shock, Trauma Injury

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Low Titer Group O Whole Blood (LTOWB)
Placebo
Tranexamic Acid (TXA)
Component Therapy (CT)
Sponsored by
Philip Spinella
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemorrhagic Shock focused on measuring Children, Pediatrics, Transfusion

Eligibility Criteria

undefined - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Children, defined as less than 18 years of age with traumatic injury 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: Hypotension for age (< 5% tile) Tachycardia for age (>95th % tile) Traumatic injury with exam findings consistent with severe bleeding (e.g., penetrating injury, hemothorax, distended abdomen with bruising, amputation of limb). Exclusion Criteria: Unknown time of injury Greater than 3 hours since time of injury History of seizure after the injury event Known allergy or hypersensitivity reaction to TXA Comatose (Glasgow Coma Score of 3) with fixed and dilated pupils suggesting nonsurvivable brain injury MTP activated but no blood products given Patients who required an ED thoracotomy or received more than 5 consecutive minutes of cardiopulmonary resuscitation (prior to receiving randomized blood products) Patients who are obviously pregnant on clinical examination Known prisoners as defined in protocol Known ward of the state Isolated hanging, drowning or burns Previous enrollment in MATIC-2 Prior study opt-out with bracelet

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Other

    Other

    Other

    Other

    Arm Label

    Group 1 (LTOWB+TXA)

    Group 2 (LTOWB+Placebo)

    Group 3 (TXA+CT)

    Group 4 (CT+Placebo)

    Arm Description

    Concurrent administration of LTOWB and TXA.

    Concurrent administration of LTOWB and Placebo

    Concurrent administration of TXA and CT

    Concurrent administration of CT and Placebo

    Outcomes

    Primary Outcome Measures

    24 hours all cause mortality

    Secondary Outcome Measures

    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.
    24 hours total blood product transfusion volumes
    Total blood product transfusion in 24 hours after enrollment.

    Full Information

    First Posted
    September 27, 2023
    Last Updated
    October 9, 2023
    Sponsor
    Philip Spinella
    Collaborators
    Biomedical Advanced Research and Development Authority
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06070350
    Brief Title
    Massive Transfusion in Children-2: A Trial Examining Life Threatening Hemorrhage in Children
    Acronym
    MATIC-2
    Official Title
    Massive Transfusion in Children: a Platform RCT of Whole Blood Compared to Component Therapy and Tranexamic Acid to Placebo in Life-threatening Traumatic Bleeding
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 1, 2024 (Anticipated)
    Primary Completion Date
    March 1, 2028 (Anticipated)
    Study Completion Date
    September 1, 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Philip Spinella
    Collaborators
    Biomedical Advanced Research and Development Authority

    4. Oversight

    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
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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
    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: Determine the effectiveness of LTOWB to reduce all-cause 24-hour mortality compared to CT in children with traumatic life-threatening hemorrhage. 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: Acute kidney injury Acute respiratory distress syndrome Sepsis Thromboembolism: arterial and venous Markers of hemolysis Alloimmunization in Rh negative female recipients of Rh+ LTOWB Transfusion-related adverse events 8 Serious Adverse Events (SAEs) Mechanistic Objectives are to: Define trauma induced coagulopathy (TIC) according to measures of shock, hemostasis, and endothelial and immune function. 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. 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hemorrhagic Shock, Trauma Injury
    Keywords
    Children, Pediatrics, Transfusion

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Crossover Assignment
    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 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.
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    The research pharmacy at each site will produce a placebo for TXA that matches the volume of the actual TXA dose. Syringes 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.
    Allocation
    Randomized
    Enrollment
    1000 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Group 1 (LTOWB+TXA)
    Arm Type
    Other
    Arm Description
    Concurrent administration of LTOWB and TXA.
    Arm Title
    Group 2 (LTOWB+Placebo)
    Arm Type
    Other
    Arm Description
    Concurrent administration of LTOWB and Placebo
    Arm Title
    Group 3 (TXA+CT)
    Arm Type
    Other
    Arm Description
    Concurrent administration of TXA and CT
    Arm Title
    Group 4 (CT+Placebo)
    Arm Type
    Other
    Arm Description
    Concurrent administration of CT and Placebo
    Intervention Type
    Biological
    Intervention Name(s)
    Low Titer Group O Whole Blood (LTOWB)
    Intervention Description
    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
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo will be made by the research pharmacy at each of the clinical sites
    Intervention Type
    Drug
    Intervention Name(s)
    Tranexamic Acid (TXA)
    Intervention Description
    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.
    Intervention Type
    Biological
    Intervention Name(s)
    Component Therapy (CT)
    Intervention Description
    Component Therapy (CT) will be RBCs, plasma and platelet units in a 1:1:1 unit ratio. This will be given with Placebo
    Primary Outcome Measure Information:
    Title
    24 hours all cause mortality
    Time Frame
    24 hours
    Secondary Outcome Measure Information:
    Title
    6-hour, 72-hour and 28-day survival
    Description
    Cumulative survival over time through 28 days post-enrollment: includes 6-hour, 72-hour and 28-day survival.
    Time Frame
    6, 72 hours and 28 days
    Title
    24 hours total blood product transfusion volumes
    Description
    Total blood product transfusion in 24 hours after enrollment.
    Time Frame
    24 hours

    10. Eligibility

    Sex
    All
    Maximum Age & Unit of Time
    17 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Children, defined as less than 18 years of age with traumatic injury 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: Hypotension for age (< 5% tile) Tachycardia for age (>95th % tile) Traumatic injury with exam findings consistent with severe bleeding (e.g., penetrating injury, hemothorax, distended abdomen with bruising, amputation of limb). Exclusion Criteria: Unknown time of injury Greater than 3 hours since time of injury History of seizure after the injury event Known allergy or hypersensitivity reaction to TXA Comatose (Glasgow Coma Score of 3) with fixed and dilated pupils suggesting nonsurvivable brain injury MTP activated but no blood products given Patients who required an ED thoracotomy or received more than 5 consecutive minutes of cardiopulmonary resuscitation (prior to receiving randomized blood products) Patients who are obviously pregnant on clinical examination Known prisoners as defined in protocol Known ward of the state Isolated hanging, drowning or burns Previous enrollment in MATIC-2 Prior study opt-out with bracelet
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jane Luce
    Phone
    412-383-7853
    Email
    jane.luce@pitt.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Philip C Spinella, MD
    Organizational Affiliation
    Univesrity of Pittsburgh
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing 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.

    Learn more about this trial

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

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