Questions and Answers
What is the purpose of this study?
The purpose of this study is to determine if Tranexamic Acid (TXA) given as soon as possible after injury to patients suspected of having a traumatic brain injury (TBI) have a better outcome than patients with TBI who are not given TXA.
Traumatic Brain Injury is a major public health problem. 1.7 million people suffer from a TBI in the US every year, making TBI a leading cause of death and disability. Approximately 10,000 Alabamians receive a traumatic brain injury each year. Of that number, 500 die and 1,500 become permanently disabled.
· 53,000 Americans die every year from TBI.
· 8 teenagers die every day in the US from TBI
· 5 million Americans are living with TBI related disabilities
· 300,000 soldiers suffer from TBI or post-traumatic stress disorder (PTSD)
· TBI is highly interconnected with other neurological disorders.
· have a very high rate of post-traumatic stress disorder
· are 50% more likely to suffer from depression
· are 5-times more likely to develop Alzheimer’s disease
· are significantly more likely to suffer other long-term neurodegenerative consequences.
Treatment for severe injury must be initiated quickly to limit the extent of injury. Very few treatments have been scientifically tested or when they are tested, the treatment is frequently not given early enough (at the scene of the injury) to have an effect. More research must be done to guide treatment for this common, disabling and potentially lethal health problem.
Who will be included in the study?
Patients who suffer a TBI and meet the eligibility criteria may be enrolled in this study. Eligibility criteria describe patient characteristics that are required to be included in the study as well as characteristics that would exclude the patient from the study.
Subjects must meet ALL of the following:
· Blunt or penetrating traumatic mechanism consistent with traumatic brain injury
· Prehospital Glasgow Coma Score (GCS) score ≤ 12 at any time prior to randomization and administration of sedative and/or paralytic agents
· Prehospital systolic blood pressure (SBP) ≥ 90 mmHg prior to randomization
· Prehospital intravenous (IV) access
· Estimated Age ≥ 15 (or estimated weight > 50 kg if age is unknown)
· EMS transport to UAB Hospital
Subjects are ineligible if they meet ANY of the following:
· Prehospital GCS=3 with no reactive pupil
· Estimated time from injury to start of study drug bolus dose > 2 hours
· Unknown time of injury
· Suspicion by EMS of seizure activity or known history of seizures, thromboembolic disorders, acute MI or stroke
· Cardiopulmonary resuscitation (CPR) by EMS prior to randomization
· Burns > 20% total body surface area (TBSA)
· Suspected or known prisoners
· Suspected or known pregnancy
· Prehospital TXA given prior to randomization
· Subjects wearing an “Opt-out of ROC Research” bracelet.
How will the treatment be given?
Participating Emergency Medical Services (EMS) agencies will carry blinded, sealed packages. After life-saving interventions are performed, the EMS provider will assess the patient and determine if they are eligible. Eligible patients will be randomly assigned to receive one of three treatments.
1. 1 gram of TXA before hospital arrival and 1 gram TXA given over 8 hours in the hospital, or
2. 2 grams of TXA given before hospital arrival and no TXA given in the hospital with a placebo of normal saline given for 8 hours, or
3. Placebo – normal saline given before hospital arrival and normal saline given for 8 hours in the hospital; no TXA will be given.
Where will the study be conducted?
The study will be conducted in at least 10 locations across the United States and Canada, including central Alabama. EMS personnel for Air Methods (LifeSaver helicopter), Bessemer Fire Department, Birmingham Fire and Rescue, Center Point Fire District, Hoover Fire Department, NorthStar EMS, Regional Paramedical Services will be trained and participate in this study.
How many patients will be enrolled in the study?
A total of 1,002 patients will be enrolled across all participating ROC sites in the United States and Canada. In Alabama we anticipate almost 200 people will be enrolled in this study.
When will the study start?
The first patient is expected to be enrolled in the summer of 2014. The start time will be different at each of the ROC sites depending on when they receive approval to begin the study.
How long will it take to complete the study?
The study enrollment is expected to last approximately one year once all sites have begun enrolling.
How do patients enroll in the study?
Patients in this study will have had a severe traumatic injury. Traumatic injuries occur unexpectedly and because of the inability to predict when a traumatic injury is going to occur, a person cannot sign up ahead of time. Patients may be unconscious (unable to speak or hear) when they are enrolled in the TXA trial. Life-supporting interventions must be given immediately in the field by the paramedics. Patients are too sick to consent to immediate treatment. Therefore, the paramedics will enroll patients with a TBI into the study by opening a package and giving them what is in the kit. The contents of the packages will be randomly determined like flipping a coin.
How can research be done on a person without the person’s permission?
There are serious medical emergency situations where patients are too sick or unconscious to give permission to be enrolled in a study. Severe traumatic injury is one of those situations. The TXA study will be 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 under carefully controlled circumstances. This is in recognition of the unique kind of emergency medical situations in which patients or family members cannot give informed consent before treatment as well as the need to allow emergency care to advance through research.
According to FDA regulations, to qualify for EFIC, the research study must involve participants suffering from a life-threatening disease process or injury for which the current standard of care is associated with a very high failure or mortality rate. In addition, there must be reasonable evidence that the research has the potential to provide real and direct benefit to the patient. Studies must be held to the highest ethical standards. The ROC studies have undergone many independent rigorous reviews to ensure that they meet these standards.
The use of a randomized clinical trial such as this is the “gold standard” for determining what works best for people. For treatments that must be given immediately to be effective, EFIC research is considered appropriate by federal regulatory bodies and many ethicists who study this field. The obligation to improve standard treatments that yield poor results in life-threatening conditions is also considered an ethical imperative, as is maintaining individual rights of citizens. In EFIC trials, citizens received standard treatment in addition to research treatment. To be tested in this fashion, the research treatment has to have shown promise in earlier or smaller studies.
If a family member is present when the patient has a traumatic injury, why is the family not asked for permission?
There isn’t 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. Severe traumatic injury is an extreme emergency during which the patient could potentially die if treatment is not begun immediately. Patients suffering a traumatic injury 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. In rare circumstances, if feasible, the paramedic will read a “Study Information Script” to the patient or the patient’s legally authorized representative to provide an opportunity to verbally object to study enrollment.
Once the injured patient reaches the emergency department, will the patient and/or family member be told about the study?
The study treatment will continue when the patient arrives in the emergency department. If it is feasible, an attempt will be made to obtain informed consent from the patient’s legally authorized representative or directly from the patient, if possible. The study continues to 6 months following injury with an interview of the patient or patients’ family member asking how the head injury has affected their life. If informed consent is not obtained before the end of the 6 month interview date, no further efforts will be made. However, notification of the patient’s enrollment in the study will be attempted. The patient, the patient’s legally authorized representative or family member will be given the opportunity to withdraw the patient from further study participation and will be provided instruction for how to do so.
Are there any risks to the patient?
As is possible with any new treatment, there are risks involved. Patient safety is carefully monitored and recorded for any complications of study treatments. The patients in this study will be selected to receive 1gram of TXA bolus with 1 gram of TXA maintenance infusion versus 2 grams of TXA bolus with placebo maintenance infusion versus placebo bolus and placebo maintenance infusion. At higher doses than these, the use of TXA has been associated with seizures and an increased risk of clotting events in the body (e.g., MI, PE, ischemic stroke, or symptomatic DVT).
Can a person opt out of this research?
Yes. We will provide a “Opt Out of ROC Research” wristband for those people who do not want to be enrolled in the study. You can contact us by calling the Alabama Resuscitation Center at 205-934-9532 or email firstname.lastname@example.org.