UC Davis emergency medicine researchers have been awarded a grant from the National Institutes of Health (National Heart, Lung, and Blood Institute) to investigate the safety and efficacy of a drug known to stop bleeding in injured adults for use in cases of pediatric trauma. Trauma is the nation’s leading cause of death and disability in children – greater than all other causes combined. The research, if successful, would lead the way toward two large clinical trials to fully evaluate the drug – tranexamic acid (TXA) – in severely injured children with either abdominal injuries or traumatic brain injuries.
Led by Drs. Daniel Nishijima and Nathan Kuppermann, the UC Davis pilot study is a two-year project designed to model and identify patient enrollment procedures and fill in essential information gaps in preparation for a large-scale, multi-site clinical trial.
“This initial work at UC Davis Medical Center is a crucial step in eventually being able to test a potentially life-saving treatment for pediatric trauma victims,” said Kuppermann, who is a professor and chair of emergency medicine. “TXA has been shown to save the lives of adults with trauma, and many groups around the world are hoping for someone to investigate its use in children. With this new NIH grant, we now have that important opportunity.”
TXA is an antifibrinolytic drug that promotes blood clotting by preventing blood clots from breaking down, and as a consequence, reduces bleeding. The drug has been extensively used in surgeries in both adults and children to decrease blood transfusion requirements. The success of TXA in surgery led to studies of its use in adult trauma, where researchers found that if administered within three hours of injury, TXA reduced the risk of hemorrhagic death by approximately 33 percent. The drug is now considered a standard treatment in adults with traumatic bleeding, and it is estimated to save more than 100,000 lives per year worldwide.
“Because children are different than adults with regard to their anatomy, physiology and psychological development, the results of the TXA in adult trauma cannot be extrapolated to injured children,” said Nishijima, an associate professor and associate research director in the department of emergency medicine, and co-principle investigator of the new study. “The use of this drug, which prevents the breakdown of blood clots in injured children, is a key research priority that could have national and worldwide benefits.”
Hemorrhage is the primary cause of death in the first 24 hours after trauma and accounts for 40 percent of all trauma related deaths. Traumatic hemorrhage is often exacerbated by a number of physiologic factors related to the traumatic event. There have been no prospective controlled trials of TXA in injured children, and a review of available data and information suggests that the drug has been only rarely used for pediatric trauma in the U.S.
The UC Davis research team noted that conducting a multi-center, clinical trial in critically ill children is very challenging. Smaller recruitment pools and complicated parental consent and patient approval procedures have stifled other clinical trials involving acutely injured children, resulting in an insufficient number of study subjects and delays in meeting regulatory requirements.
“Pilot studies are particularly relevant and important when it comes to pediatric research, where clinical teams face narrow therapeutic windows and complicated consent and other study processes,” added Kuppermann. “We think our study could provide a clear “go-no go” answer regarding the practicality of being able to conduct the larger and more definitive clinical trials on severely injured children with either hemorrhagic abdominal injuries or traumatic brain injuries.”
In addition to Kuppermann and Nishijima, the collaborative project includes investigators from the UC Davis departments of surgery, neurological surgery, pathology and laboratory medicine, radiology and psychology, as well the UC Davis Good Manufacturing Practice facility in Sacramento. The study will be conducted at UC Davis Children’s Hospital, Children’s Hospital of Philadelphia, Nationwide Children’s Hospital (Ohio State University), and Primary Children’s Hospital (University of Utah).