Clinical trial NCT06070350: Massive Transfusion in Children-2: A Trial Examining Life Threatening Hemorrhage in Children
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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hemorrhagic Shock
Trauma Injury
Keywords: Children
Pediatrics
Transfusion
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2023-10-06
Enrollment: 1000
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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

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:

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.

Eligibility criteria: 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

Primary outcomes:
measure: 24 hours all cause mortality
timeFrame: 24 hours
Secondary outcomes:
measure: 6-hour, 72-hour and 28-day survival
timeFrame: 6, 72 hours and 28 days
measure: 24 hours total blood product transfusion volumes
timeFrame: 24 hours
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University-Arthur M. Blank Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University-Scottish Rite Hospital
state: Georgia
city: New Orleans
country: United States
facility: Tulane School of Medicine
state: Louisiana
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University of St. Louis
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Wake Forest
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Memphis
country: United States
facility: LeBonheur Children's Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Children's Memorial Hermann Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Seattle
country: United States
facility: University of Washington Harborview
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Univesrity of Pittsburgh
name: Philip C Spinella, MD
role: PRINCIPAL_INVESTIGATOR
References: