Frequently Asked Questions about the TAP Trial at Hennepin

What is Kcentra®/4-factor Prothrombin Complex Concentrate?
Kcentra® (4-factor Prothrombin Complex Concentrate), is a blood clotting factor replacement product. It contains clotting factors II, VII, IX, and X, as well as Protein C and Protein S. Kcentra® is an Food and Drug Administration (FDA) approved product. It is currently used to reverse the effects of drugs given to “thin” the blood in patients who are experiencing bleeding and/or require surgery.

Who will be included in the study?
We will include patients who have been injured, and who are deemed to require a blood transfusion. We know that such patients are at high risk of dying. The formal eligibility criteria (which describe the patient characteristics that are required to be included in the study, as well as characteristics that would exclude the patient from the study) are as follows:

1. (a) Estimated or actual age ≥ 15 years; and (b) Estimated or actual weight ≥ 50 kg (110 lbs)
2. Traumatic injury with: (a) confirmed or suspected acute major bleeding; and / or (b) Revised Assessment of Bleeding and Transfusion score ≥ 2
3. Activation of massive transfusion protocol
4. At least 1 unit of blood product spiked (transfusion bag connected to an intravenous fluid line and ready to start)
5. Anticipated start of investigational product infusion within 90 minutes after arrival at the hospital

Where will the study take place?
The study will take place in our Emergency Department.

Is Kcentra® already in use?
Kcentra® is widely used to reverse the effect of blood-thinning medication. It is not currently approved for use in injured patients, because it has not been evaluated in this setting. The TAP trial will provide us with the data to decide whether it should be used in injured patients – or not.

What treatments do injured patients currently receive?
The standard treatment of injured patients who are bleeding involves the transfusion of different types of blood products, as well as the use of medications to help the blood clot better (and surgery, to stop the bleeding). Even with these treatments 10-30% of patients suffering from a serious traumatic injury die. Importantly, everyone that participates in this trial will receive standard care. In addition, some of the patients will receive Kcentra®.

How will the treatment be given?
The treatment (Kcentra® or placebo) will be given as an intravenous (into a vein) infusion, which lasts about 10-15 minutes. The treatment will be given in addition to all usual care. No care will be withheld because of the research trial.

What happens after the infusion has been completed?
There are no other research treatments once the infusion has been completed. We will record whether patients live or die, and carefully monitor them for any complications. There are no additional hospital or clinic visits for the research study. 

Will all patients receive Kcentra®?
No. In order for us to be able to determine whether Kcentra® makes a difference, we will give it to half the patients. The other half will receive a placebo. When an injured patient is brought to our emergency department, and deemed to meet the criteria for participation in the TAP trial, doctors will open a special pack. The pack contains a vial, of either Kcentra®, or placebo. The medical team looking after the patient will not know which of the two the patient received. This will allow us to evaluate the results in an unbiased way.

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

Where will TAP be conducted?
TAP will involve approximately 100 trauma centers across the United States, and a further 40 trauma centers in other countries.

How many patients will be enrolled in TAP?
We are planning to enroll up to 8,000 patients.

When will the study start?
Early 2023

How long will it take to complete the study?
We estimate that it will take 2-3 years to complete the study.

How will patients be enrolled in TAP?
Patients in this study will have suffered a serious and potentially life-threatening injury, causing significant blood loss, and requiring immediate lie-saving interventions. These types of injuries occur unexpectedly, and it is not possible for people to sign up to take part ahead of time. Most patients will be unconscious (unable to speak or hear) and too sick to consent to immediate treatment, or participation in the study. Doctors will therefore enroll patients into the study without their consent.

How can research be done on a person without the person’s permission?
Research is normally only conducted with the express permission of the patient. However, it is often not possible to obtain patients’ consent to study treatments that are administered in life-threatening emergencies – but such research still has to be done. The TAP 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 usually 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. Patients suffering significant blood loss may be unconscious or too sick to discuss their treatment, and any time taken to discuss their treatment with family deprives the patient of immediately starting life-saving measures.

Will the patient and/or family member be told about the study?
Yes, we will inform patients, and their relatives, as soon as possible. Most of the time, the treatment (Kcentra® or placebo) will have been given by the time we are able to reach relatives, or patients themselves are able to take in such information. If a patient, or legally authorized representative, decides that they do not wish to continue to be part of the study, then no further data will be collected.

Are there any risks to the patient?
Virtually any treatment involves some risks. However, from what we know about Kcentra®, these risks are small (particularly in comparison to the risk of dying as a result of blood loss). Patient safety is carefully monitored and we record any complications of study treatments. Known risks of Kcentra, which are all much less than the risks of dying from blood loss from injuries include:

Frequency: Common (greater than or equal to 1 in 100)

• Formation of a blood clot in a blood vessel, blocking the vessel – Blood clots can cause swelling of an arm or leg, pain and shortness of breath if they occur in the lungs, stroke, or heart attack. Blood clots may rarely be fatal.
• Headache;
• Body temperature increased

Frequency: Uncommon (greater than or equal to 1 in 1,000)

• Mild allergic reaction;

Frequency: Not known

• Formation of blood clots in small blood vessels throughout the body that can cut off blood flow to organs or lead to bleeding
• Severe allergic reactions (anaphylaxis)
• Your body to have a reaction to ingredients in the study drug that may cause it to be ineffective

It is possible that an extra intravenous catheter (IV tube or IV line) will need to be placed in a vein to administer study drug. Possible side effects to having an IV include bleeding at the site of the catheter, infection, pain, redness, and bruising.

KCentra is made from human blood that may contain infectious germs such as viruses or bacteria. However, the likelihood of transmitting infectious germs with KCentra is very low, due to the steps undertaken during the manufacturing of the study drug to remove these germs.

Will a patient be compensated if they are harmed by participating in this trial?
If a patient suffers a physical injury caused directly from KCentra or study procedures, the study sponsor will pay for the reasonable costs of medical treatment if:

• The study drug was properly administered according to the study plans;
• The study procedures were properly performed and required by the study plan;
• Your injury was not deliberately caused;
• The Study Doctor was immediately notified about the injury, and;
• The medical advice of the Study Doctor was followed.

Can a person opt out of this research? 
Yes. We will provide an “Opt Out of Trauma Research” wristband for those people who do not want to be enrolled in the study. Link to "Opt Out of Trauma Research" 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 TAP research study?
Research staff can be contacted at (205) 934-5890 or via email at cis@uabmc.edu.