ANN ARBOR, Mich. — Every twenty-eight seconds, someone in America suffers a stroke, a massive seizure, a brain or spinal cord injury, or another major emergency affecting the brain, spine or nerves. Every two minutes, someone dies from one of these conditions. Many others are left permanently disabled.
To reduce this toll, it will take better treatments that can be delivered in the first minutes and hours after neurological emergencies occur. But many barriers stand in the way of studying new treatments in enough patients to show how well they work.
This week, a team of researchers from around the country will gather in Michigan to kick off an unprecedented national effort to break down those barriers. The meeting will officially launch the Neurological Emergencies Treatment Trials network, or NETT, which will be a permanent backbone that will allow a broad variety of studies to be conducted in ambulances and hospitals nationwide.
The network is funded by a $7.7 million, five-year grant from the National Institute for Neurological Diseases and Stroke, part of the National Institutes of Health.
Because it involves so many sites where brain and spine emergencies are treated, NETT will overcome one of the biggest roadblocks to finding better emergency treatments: having enough eligible patients with the same condition at any single hospital. By studying patients at many hospitals, NETT will gather information on what works, and what doesn't, faster than ever before – and share that knowledge so that all patients can benefit.
The University of Michigan Health System is the home to the NETT's clinical coordinating center, which will coordinate the network's 11 "hub" centers at major medical centers. Each of those hubs will partner with many "spoke" hospitals and emergency medical response companies around the country.
This week's kickoff is something that Bill Barsan, M.D., has been working toward for more than three years. He's the chair of the U-M's Department of Emergency Medicine, and principal investigator of the NETT clinical coordinating center.
"Neurologic emergencies, including stroke, head trauma and seizures, are the leading cause of brain damage in the United States. In patients with these problems, the first minutes and hours of treatment are very important. Our mission is to improve outcomes of patients with acute neurological problems through innovative research focused on patient care that starts in the ambulance and in the emergency department," Barsan says. "NETT will give us the framework to test medications, patient management strategies and other treatments on a large scale and over a short timeframe."
In addition to UMHS, NETT involves a Statistical & Data Management Center at the Medical University of South Carolina, headed by Yuko Palesh, Ph.D., and researchers at 11 hubs: Wayne State University and Henry Ford Health System in Detroit; Emory University; the Medical College of Wisconsin; Temple University; the University of Pennsylvania; the University of Arizona; the University of California, San Francisco; the University of Cincinnati; the University of Kentucky; and the University of Minnesota. The network's web site is nett.umich.edu.
At each of the hub sites, NETT will involve emergency physicians, neurologists, neurosurgeons, and others. Each hub hospital will have at least two spoke hospitals, and some will have many more. Spoke hospitals will include community and regional hospitals, giving NETT the ability to test new treatments in a ‘real world' setting beyond major university medical centers.
The CCC will be administered in partnership with U-M's Michigan Institute for Clinical and Health Research, with Dan Lowenstein, M.D., of UCSF serving as its Co-Principal Investigator. Co-investigators in the CCC are Art Pancoli, M.D. from the University of Cincinnati, Lewis Morgenstern, M.D., director of the U-M Stroke Program and a professor of neurology, neurosurgery and emergency medicine at U-M, and Robert Silbergleit, M.D., associate professor of emergency medicine at U-M. Robin Conwit, M.D., of the NINDS Clinical Trial Group, serves as the NETT program director.
This week's meeting will bring together the steering committee and lead investigators, who will discuss the new network's organization, data management, and issues related to specific studies.
One of those issues is the process for conducting studies of treatments that must be given before a full "informed consent" to participate can be obtained from the patient or his or her legal representative. Federal regulations allow for such studies to be performed under an "emergency exception to informed consent", but they can only be done under very limited and controlled circumstances, and only after federal permission is received and the community is informed and consulted about the study.
Barsan explains that a signed informed consent document is usually required in advance for every person who takes part in a clinical trial. But the very nature of neurological emergencies such as head injury or seizures means that patients who might benefit from a rapidly delivered therapy could be unconscious or unable to understand what's happening. Often, their spouse, parent or other legal representative isn't with them at the time the emergency occurs. And the process of explaining a study and obtaining truly informed consent from anyone can take an hour or more – by which time it is too late to deliver many emergency treatments.
NETT will aim to begin its first trial in late 2007, if it receives the U.S. Food & Drug Administration's approval for waiver of informed consent. Called the RAMPART trial, it will involve patients experiencing status epilepticus — a severe prolonged form of seizure lasting more than 30 minutes that can be life-threatening. Silbergleit is the principal investigator of RAMPART, which will randomly assign patients to receive one of two anti-seizure medications before they arrive at the hospital. Paramedics will use special kits that will contain an active form of only one medication.
Specifically, the study will test a muscle injection of one drug against the more common treatment, an intravenous dose of another drug. Because IVs can be hard to start quickly in patients who are seizing violently, the study may help give paramedics a different option for treating patients' seizures and preventing them from injuring themselves before they receive more treatment at a hospital. If the muscle injection is found to work well, it may also be of use in situations such as poison-gas attacks where large numbers of people might experience status epilepticus at once.
Other studies being planned for the NETT network will address the form of "bleeding" stroke known as intracranial hemorrhage, the sudden facial-nerve paralysis known as Bell's palsy, and traumatic brain injury. Other potential studies are now being developed.