This effort is being led by Michael J. Bell, M.D
., director, Pediatric Neurocritical Care and Neurotrauma at Children’s Hospital and Stephen Wisniewski, Ph.D
., senior associate dean and co-director of the Epidemiology Data Center at Pitt Public Health. Dr. Bell will coordinate patient enrollment and clinical activities within the project and Dr. Wisniewski will coordinate data collection and the statistical analysis for this project.
The five-year study aims to provide compelling evidence to change clinical practices and provide recommendations for guidelines that could immediately improve outcomes for injured children.
The researchers plan to enroll 1,000 children up to 18 years old from over 36 locations in the United States and abroad to compare the effectiveness of immediate treatments of the injury, including strategies to lower intracranial pressure, strategies to treat secondary injuries and the delivery of nutrients in a study that is called the Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial.
“Incremental improvement in outcomes of traumatic brain injury could make enormous differences for the health of children, but such advances have remained elusive,” said Dr. Bell, also associate professor, Critical Care Medicine and Neurological Surgery at the University of Pittsburgh School of Medicine
. “No mitigating treatments have been translated into clinical practice, so we hope this study helps us gain a better understanding of contemporary therapies.”
“Traumatic brain injury is the leading cause of death in children in the U.S. with the CDC estimating more than 7,000 children dying each year from TBI,” said Dr. Wisniewski, also professor of Epidemiology at Pitt Public Health. “Given the incidence of the condition and the outcomes from previously reported clinical studies, we estimate that up to 1.3 million life-years are at risk each year from severe TBI. Any benefits that can be gained by improving clinical practice can have enormous consequences for children right now, and for clinical trials in the future.”
The study, which is expected to more than double existing evidence-based treatment recommendations for traumatic brain injuries in children, will provide volumes of data for improved TBI research protocols that would limit variability in treatments. Such variability has led to the failure of previous randomized controlled trials. The study also will evaluate the effectiveness of six therapies encompassing three specific aims – intracranial hypertension therapies, secondary insult prevention, and metabolism.
Children with severe traumatic brain injuries where an intracranial pressure monitor is placed will be enrolled in the study. The children will receive the standard of care offered by their hospital in the United States and Europe and extensive data on their cases will be collected over the week following the injury. Outcomes will be tested at 6 months and 1 year after injury for all children.
Dr. Wisniewski plans to use statistical methods to evaluate the impact of treatments on outcomes up to one year after the injury. This will allow the researchers to determine what approach works best.
“Completion of this study will provide compelling evidence to change clinical practices, provide evidence for new recommendations for future guidelines and lead to improved research protocols that would limit inconsistencies in traumatic brain injury treatments – helping children immediately through better clinical practices and ultimately through more effective investigation,” Dr. Bell said.
“Beyond the large impact that these recommendations will have on the field of pediatric traumatic brain injury, we expect our study to lead to the development of feasible randomized controlled trials,” Dr. Wisniewski said. “Such trials are the best way to provide assurances that a recommended treatment truly has the greatest odds of healing an injured child.”
“This novel study, which includes many dedicated international physicians and scientists, has the potential to accelerate our knowledge of how to treat children who sustain severe traumatic brain injuries,” said Ramona Hicks, Ph.D., a program director at the NIH National Institute of Neurological Disorders and Stroke (NINDS), which is providing the grant support for the study. “NINDS looks forward to rapid results that will inform clinical practice within the next few years.”
Other key investigators on the project include an international group of TBI experts: Patrick M. Kochanek, M.D. and Sue Beers, Ph.D., University of Pittsburgh; P. David Adelson, M.D., Barrow’s Neurological Institute Phoenix Children’s Hospital; Jamie Hutchison, M.D., The Hospital for Sick Children in Toronto; Robert Tasker, M.D., Boston Children’s Hospital; and Monica Vavilala, M.D., University of Washington. Statisticians and epidemiologists include Tony Fabio, Ph.D., M.P.H. and Sheryl Kelsey, Ph.D., Pitt Public Health; and Joel Greenhouse, Ph.D., M.P.H., Carnegie Mellon University. Collaborators from the NIH include Deborah Hirtz, M.D., and Ramona Hicks, Ph.D.