University of Florida Health has been chosen as one of 45 institutions in the U.S. and Canada to take part in a study to determine if patients with traumatic brain injury might have better outcomes through the measurement of brain oxygenation to guide their treatment.
The study will be the first conducted at UF Health under a provision of federal regulation called “exception from informed consent,” or EFIC. This is necessary, researchers said, because a head injury is a life-threatening condition requiring immediate treatment. So, some patients will be enrolled without consent if a family member or other representative is not readily available.
Traumatic brain injury, or TBI, is a leading cause of death and disability worldwide. Each year, about 3.5 million Americans sustain a TBI, leading to about 50,000 deaths. Scientists have struggled for decades to design new and better TBI treatments.
The Brain Oxygen Optimization in Severe TBI Phase 3 trial, or BOOST3, will study differences in patient outcomes after two types of intensive treatment of TBI. The $32 million multiyear study is funded by the National Institutes of Health.
In this study, one group of subjects will have their treatment guided by intracranial pressure management, or ICP. The other group will have their treatment guided by ICP and cerebral oxygenation management. Both approaches are currently practiced in the United States. However, it is not known which works best.
In cerebral oxygenation management, physicians use a variety of methods to increase oxygen levels in brain tissue, which might include the manipulation of mean arterial or central venous pressure.
In BOOST3, patients will be randomly separated equally in the two study groups over the initial five days of ICU care. Patient outcomes will be assessed at six months. The study is expected to enroll more than 1,000 patients nationally, ages 14 or older, over five years. UF Health anticipates approximately one local patient per month will meet criteria for inclusion in the study.
These criteria include a blunt closed head injury with severe brain damage.
“We need to identify improved methods to treat people after a severe TBI,” said Lisa Merck, M.D., M.P.H., an associate professor in the UF College of Medicine’s department of emergency medicine and the vice chair of research. “The theory behind BOOST3 is to determine if maximizing cerebral oxygenation and controlling intracranial pressure together improves patient outcomes.”
Preliminary research has suggested monitoring intracranial pressure, or brain swelling, and oxygenation together might be a more effective treatment. Many hospital systems, including UF Health, have equipment to monitor brain oxygenation along with ICP, and some physicians already use it when treating TBI, Merck said.
“This study is considered to be no more than minimal risk, as both therapies are used at academic medical centers nationally,” Merck said. “Likewise, the monitoring devices have been FDA-approved for many years and are currently used across the country. But there has not yet been a clinical trial documenting that one method or the other improves patient outcomes.”
EFIC, which is found under 50.24 of the code of federal regulations, is an important tool in emergency medicine research nationally, Merck said. EFIC can only be used for certain studies that meet federal guidelines. Because head injury is a life-threatening condition requiring immediate treatment, some patients will be enrolled without consent if a family member or other representative is not available. Every attempt will be made to locate family before enrollment to allow them to decide about the patient’s participation in the study. If no one is available, the patient will be enrolled in this BOOST3 study under the EFIC process.
Under EFIC, “We will ask for informed consent from a patient’s loved one to be enrolled or continue participation in the trial, or to withdraw, at the earliest possible time,” Merck said.
The researchers’ first step: All human research is reviewed and approved by what is called an Institutional Review Board, or IRB, which is a group of scientists, non-scientists, and community members. The researchers submit their research to the IRB. For studies involving EFIC, the researchers submit a plan to the IRB outlining how they will inform the community about what they are doing.
“The community has to be aware that there is an ongoing clinical trial nationally and locally,” Merck said. “They must know that we are hoping to improve care for patients after a severe TBI, who are unable to provide consent themselves.”
To that end, the national BOOST3 team is holding community forums and focus groups, from Florida to California. At UF, these educational groups will take place in local communities over the next few months and are designed to provide information about the trial and the importance of emergency research efforts, Merck said. This community feedback is then provided to the IRB to make a final decision on approval.
An individual can choose to opt out of the BOOST3 study by requesting from study leadership a medical alert bracelet with the words “BOOST3 Declined.” Wearing the bracelet during the duration of this five-year trial will allow someone to opt out of the study enrollment, in the event they suffer a severe TBI and are unconscious, according to BOOST3 guidelines.
BOOST3 is part of The Strategies to Innovate Emergency Care Clinical Trials Network, or SIREN network. This National Institutes of Health-funded network seeks to improve outcomes of patients with neurologic, cardiac, respiratory, hematologic and trauma emergencies by identifying effective treatments administered in the earliest stages of critical care. The UF College of Medicine’s department of emergency medicine is a hub for research within the SIREN network.