Why is the MATIC-2 Trial being conducted?
Trauma is the leading cause of death in children. There have been no large-scale clinical trials to guide the best way to resuscitate children with life-threatening bleeding from traumatic injury. The MATIC-2 Trial is being conducted so that doctors can know how best to treat children who are severely injured and bleeding. 

Who will be included in the study?
We will include children who have been injured with life threatening bleeding and have blood transfusions ordered by their physicians. The formal eligibility criteria (which describe the characteristics that are required to be included in the study, as well as characteristics that would exclude a child from the study) are as follows:

Where will the study take place?
The study will take place in the hospital. Some places where injured children receive care include the Emergency Department, Operating Room, and Intensive Care Unit.

What treatments do injured patients currently receive?
There are several ways that doctors treat children in the US with severe bleeding, including with blood products and medications. Even with these treatments 30-50% of children suffering from a traumatic injury with severe bleeding die. Currently, the blood products children with life-threatening bleeding may receive include whole blood and blood components (red blood cells, plasma and platelets). Additionally, children with severe bleeding may receive a drug called tranexamic acid (TXA) which helps stabilize clots that form to stop bleeding. All of these treatments included in this study are used routinely in children with life-threatening bleeding from trauma. The purpose of this study is to determine which bundle of care is best for injured children.

Blood Products

What are blood products?
Blood products are Food and Drug Administration (FDA) approved products that are used to replace blood that is lost in injured children who are bleeding. These may include whole blood, or blood component therapy which includes red blood cells, plasma, or platelets. Blood products are widely used in injured adults and children who have major bleeding. It is not known if either whole blood or blood components are best to use in injured children to improve survival.  The MATIC-2 trial will provide us with the data to decide what blood products should be used in injured children.

What is the difference between whole blood and blood components?
Whole blood is blood that has not been separated. Blood components, or component therapy, are made from whole blood that has been separated. The separated components are plasma, red blood cells, and platelets. Some hospitals use whole blood and some use blood components for children with life-threatening bleeding due to trauma. 

Is the blood used in this study experimental?
No. The blood or blood components used in this study are the same products that hospitals normally keep in their blood banks for patients who need blood transfusions.

How will blood products be given?
The blood products (whole blood or component therapy) will be given as an intravenous (into a vein) or intraosseus (into a bone) infusion by your child’s doctor, which are both standard practices for patients with life-threatening bleeding. The treatment will be given in addition to all usual care. No care will be withheld because of the research trial.

Will all patients receive blood products?
Yes. When an injured patient is brought to our emergency department, your child’s doctor will decide if they need a blood transfusion after their injury. If they do, they may be eligible to be enrolled in the trial. If they are deemed to meet all the criteria for participation in the MATIC-2 trial, doctors will then give either whole blood or component therapy depending on the study treatment chosen for our hospital at that time. In order for us to be able to determine whether whole blood or blood component therapy are better for trauma patients, half will receive whole blood and half will receive component therapy.

Are there any risks to the patient from blood transfusion?
Virtually any treatment involves some risks. A child who is bleeding after injury would receive some combination of the study treatments as part of usual trauma care in the Emergency Department, so patients who are in this study are at no greater risk than patients who are not included in the study. The risks of receiving whole blood and component therapy or blood products are the same. Patient safety is carefully monitored, and the study team will record any complications of study treatments. 

These risks are rare, but include the following:
Allergic reaction:  An allergic reaction results from an interaction of an allergen in the transfused blood with preformed antibodies in the person receiving the blood transfusion. In some instances, infusion of antibodies from the donor may be involved. The reaction may present only with irritation of the skin or mucous membranes but can also involve serious symptoms such as difficulty breathing.

Acute hemolytic transfusion reaction (AHTR):  An acute hemolytic transfusion reaction is the rapid destruction of red blood cells that occurs during, immediately after, or within 24 hours of a transfusion when a patient is given an incompatible blood type. The recipient’s body immediately begins to destroy the donated red blood cells resulting in fever, pain, and sometimes severe complications such as kidney failure.

Delayed hemolytic transfusion reaction (DHTR):  A delayed hemolytic transfusion reaction occurs when the recipient develops antibodies to red blood cell antigens between 24 hours and 28 days after a transfusion. Symptoms are usually milder than in acute hemolytic transfusion reactions and may even be absent. DHTR is diagnosed with laboratory testing.

Delayed serologic transfusion reaction (DSTR):  A delayed serologic transfusion reaction occurs when a recipient develops new antibodies against red blood cells between 24 hours and 28 days after a transfusion without clinical symptoms or laboratory evidence of hemolysis. Clinical symptoms are rarely associated with DSTR.

Febrile non-hemolytic transfusion reaction (FNHTR):  Febrile non-hemolytic transfusion reactions are the most common reaction reported after a transfusion. FNHTR is characterized by fever or chills in the absence of hemolysis (breakdown of red blood cells) occurring in the patient during or up to 4 hours after a transfusion. These reactions are generally mild and respond quickly to treatment. Fever can be a symptom of a more severe reaction with more serious causes and should be fully investigated.

Transfusion-associated circulatory overload (TACO): overload occurs when the volume of blood or blood components are transfused cannot be effectively processed by the recipient. TACO can occur due to an excessively high infusion rate or volume or due to an underlying heart or kidney condition. Symptoms may include difficulty breathing, cough, and fluid in the lungs.

Transfusion-related acute lung injury (TRALI):  Transfusion-related acute lung injury is a serious but rare reaction that occurs when fluid builds up in the lungs but is not related to excessive volume of blood or blood products transfused. Symptoms include acute respiratory distress with no other explanation for lung injury such as pneumonia or trauma occurring within 6 hours of transfusion. The mechanism of TRALI is not well understood but is thought to be associated with the presence of antibodies in donor blood.

Transfusion-transmitted infection (TTI):  A transfusion-transmitted infection occurs when a bacterium, parasite, virus, or other potential pathogen is transmitted in donated blood to the transfusion recipient.

Risk to female children: Alloimmunization: This condition occurs when a person’s immune system creates antibodies to another blood type. It can occur when someone receives a blood transfusion that is a different blood type from their own. Alloimmunization is of no harm to your child but may impact the fetus in a future pregnancy. It is treatable with appropriate medical care. The risk of serious complications to the future fetus is less than 1%.

Tranexamic Acid

What is Tranexamic Acid?
Tranexamic acid is a medication that can help reduce bleeding by stabilizing clot formation. 

Is tranexamic acid already in use?
Tranexamic acid is widely used in injured adults and in some children who have major bleeding. It is not used consistently in injured children, because of the lack of high-quality research data in this setting. The MATIC-2 trial will provide us with the data to decide whether it should be used in injured children – or not.

How will tranexamic acid be given?
The treatment (tranexamic acid or placebo) will be given as an intravenous (into a vein) infusion or intraosseous (into a bone) if needed, which is the standard of care for use of this medication in the case of life-threatening bleeding. The treatment will be given in addition to all usual care. No care will be withheld because of the research trial.

Will all patients receive tranexamic acid?
No. For us to be able to determine whether TXA makes a difference, we will give it to half the patients. The other half will receive salt water. 

Are there any risks to the patient from tranexamic acid?
Virtually any treatment involves some risks. A child who is bleeding after injury would receive some combination of the study treatments as part of usual trauma care in the Emergency Department, so the risks of the study are no greater than the risks of usual trauma care. Patient safety is carefully monitored, and the study team will record any complications of study treatments. Known risks of tranexamic acid include:

Thromboembolic Risk: Venous and arterial thrombosis or thromboembolism has been reported in patients treated with TXA. Risk is higher with concomitant use of TXA in Sodium Chloride Injection and medical products that are pro-thrombotic, as the risk of thrombosis may be increased. These medications include, but are not limited to, Factor IX Complex concentrates, Anti-inhibitor Coagulant concentrates, and hormonal contraceptives. 

Seizures: Tranexamic acid may cause seizures, including focal and generalized seizures. The most common setting for tranexamic acid-induced seizures has been during cardiovascular surgery, which uses doses of up to ten-fold higher than the dose in MATIC-2. 

Hypersensitivity Reactions: Cases of hypersensitivity reactions, including anaphylactic reactions, have occurred with use of intravenous tranexamic acid. 

Dizziness: TXA may cause dizziness. Concomitant use of other drugs that may also cause dizziness may worsen this effect. 

What other research activities will occur?
A small amount of blood (1 teaspoon) will be drawn at three time points during the first day that your child is in the hospital. This will be used to study the mechanisms behind why some treatments work better in some children compared to others. 

Are there any activities planned once my child is discharged from the hospital?
No, there are no additional hospital or clinic visits for the research study.  We will only record information from the medical record until your child is released from the hospital, or for a maximum of 28 days (whichever is earlier).  

Who has access to patient research records?
The FDA may inspect research records of your hospitalization.

Where will MATIC-2 be conducted?
MATIC-2 will involve approximately 20 trauma centers across the United States.

How many patients will be enrolled in MATIC2?
We are planning to enroll up to 1,000 patients.

When will the study start?
October 2024

How long will it take to complete the study?
We estimate that it will take 4 years to complete the study.

How will patients be enrolled in MATIC-2?
Children in this study will have suffered a serious and potentially life-threatening injury, resulting in significant blood loss. Because blood transfusions and lifesaving care must begin very soon after injured children arrive at the hospital, it is not possible for guardians to provide consent in advance to enter a study. Doctors will therefore enroll children into the study without obtaining parental consent in advance and get consent for continued participation after the child is stable.

Why is research being done on a person without the guardian’s permission in advance?
Research is normally only conducted with the express permission of the patient/guardian. However, it is often not possible to obtain patient or guardians’ consent to study treatments that are administered in life-threatening emergencies – but such research still has to be done. The MATIC-2 trial will be therefore conducted under federal regulations that allow an exception from informed consent (EFIC).

What is exception from informed consent?
In 1996, the Food and Drug Administration (FDA) developed specific regulations to permit emergency research without prospective consent, in special circumstances, and with additional safeguards. These regulations recognize that there are situations in which patients or family members cannot give informed consent – but that there is also a need to advance emergency care, through research.

If a family member or other legally authorized representative is present when the patient arrives in hospital, will they be asked for permission?
Yes – if there is time. In order to give permission to participate in a study, it is important that the person giving permission understands what is being said to them and can make a well-informed decision. Family members are understandably very upset during a medical emergency and are not able to concentrate or comprehend what is being said during the emergency. A serious injury is an extreme emergency during which the patient could potentially die if treatment is not begun immediately. Children suffering significant blood loss are very sick, and any time taken to discuss their treatment with family deprives the child of immediately starting life-saving measures.

Will the patient and/or family member be told about the study?
Yes, we will inform families as soon as possible about the research study. Most of the time, the treatment will have been given by the time we are able to reach a family member, and the parent/guardian is able to take in such information once a child is stable. If a parent or guardian decides that they do not wish for their child to continue to be part of the study, then no further data or blood samples will be collected.

Will there be any cost to my child for participating in this trial?
No, there are no costs to you or your health-care payer/insurer for continued participation in this study. Clinical care provided will be charged in the usual manner as part of your standard medical care (care you would receive even if you were not participating in this research study).

Will my child be compensated for participating in this trial?
No, you will not be paid for participation in this research study.

Will my child be compensated if they are harmed by participating in this trial?
The hospital and their associates who provide services recognize the importance of your voluntary participation in their research studies. These individuals and their staff will make reasonable efforts to minimize, control, and treat any injuries that may arise because of this research. If you believe that you are injured because of the research procedure being performed, please immediately contact the Study Doctor at your hospital. Emergency medical treatment for injuries solely and directly related to your participation in this research study will be provided to you by the study site. It is possible that the hospital may bill you or your insurance provider for the costs of this treatment. There is no plan for monetary compensation. You do not, however, waive any legal rights by agreeing to participate in the study.

Can a person opt out of this research? 
Yes. We will provide an “Opt Out of MATIC-2” wristband for those people who do not want to be enrolled in the study. Link to "Opt Out of MATIC-2" page, click here. 

What sites are participating in this research? 
The list of sites participating in this research is here. Click Here.

Who can answer questions about the MATIC2 research study?
Research staff can be contacted at xxx-xxx-xxxx or xxx-xxx-xxxx