UCSF Leads Neurological Emergency Medicine Study in San Francisco Area Hospitals

In the fast-paced world of emergency medicine, doctors and paramedic first responders must solve problems fast and efficaciously. This critical time frame is especially important when a patient exhibits neurological damage and is having seizures. UCSF’s Claude Hemphill, MD, director of the Neurocritical Care Program at San Francisco General Hospital (SFGH), is leading a team for the San Francisco portion of a national study to determine the best treatment for a prolonged seizure called status epilepticus. The study will compare the effectiveness of two seizure-stopping medications delivered in two different ways — via muscle injection or intravenously — to immediately stop the seizure activity of patients with continuous seizures, also known as status epilepticus. Both types of medication are commonly used to treat status epilepticus, but it is not yet known which delivery method is most successful in the quickest time frame. The study, known as Rapid Anticonvulsant Medication Prior to Arrival Trial, or RAMPART, involves all emergency departments, ambulances and first responders in the city and county of San Francisco. Hemphill, associate professor of neurology and neurological surgery at UCSF, is principal investigator of the project that endeavors to enroll 100 patients in San Francisco and 750 nationwide. Co-investigators include Geoff Manley, MD, PhD, professor of neurological surgery and co-director of the SFGH Brain and Spinal Injury Center; Wade S. Smith, MD, PhD, director of the UCSF neurovascular service; Alan Gelb, MD, clinical professor and chief of Emergency Services at SFGH; Prasunthi Ramanujam, MD, researcher in the newly formed UCSF Department of Emergency Medicine; and Karl Sporer, MD, medical director of San Francisco Fire Department Emergency Medical Services. Collaborators include physicians from emergency medicine, neurology, neurological surgery and intensive care medicine at each participating hospital as well as the San Francisco Fire Department paramedic division and the San Francisco Emergency Medical Services Agency. The study is slated to kick off in January 2009. “Every hospital with an emergency department in San Francisco is participating,” said Michele Meeker, RN, nurse coordinator of the project. “Emergency responders are trained in the study protocol, and through this project, we hope to learn how best to treat status epilepticus in the future. The results of the study should be very helpful to epilepsy sufferers and their caregivers as well as patients who have first-time emergency seizures. Depending on which drug delivery method works best, patients could keep the appropriate medication with them, lessening their chances of an emergency room visit,” said Meeker. Status epilepticus is a medical emergency characterized by unstoppable seizure activity and unconsciousness. While epilepsy is the most common cause, other causes include traumatic brain injury, brain tumor, stroke, alcohol intoxication and illicit drug use. Network to Improve Emergency Care The study is part of a National Institutes of Health initiative known as the Neurological Emergencies Treatment Trials (NETT) network, which was created to improve the immediate care of neuroemergencies with treatments delivered within minutes rather than hours. NETT initiatives also explore the narrow window of opportunity existing in the treatment of neurological damage from pathologies including stroke, traumatic brain injury, seizures and meningitis. Hemphill and colleagues have formed the San Francisco Neurological Emergencies Trials (SF NETT) at UCSF, one of 17 academic centers selected as a “hub” for the NETT. Each hub acts as a local coordinating center for other participating hospitals, known as “spokes.” The UCSF hub is in the Brain and Spinal Injury Center at San Francisco General Hospital. Spoke hospitals include all San Francisco ambulance destination hospitals — UCSF Medical Center, California Pacific Medical Center (CPMC) Pacific campus, CPMC Davies campus, CPMC St. Luke’s campus, Kaiser Permanente San Francisco Medical Center, St. Francis Memorial Hospital and St. Mary’s Medical Center — as well as Highland General Hospital in Oakland. The goal of NETT and SF NETT is to create and maintain a clinical research infrastructure to perform streamlined phase III clinical trials of new treatments for neurological emergencies, including status epilepticus, traumatic brain and spinal cord injury, and stroke. In addition to RAMPART, planned NETT clinical trials include ALIAS (high-dose albumin therapy for neuroprotection in acute ischemic stroke) and PROTECT (progesterone for traumatic brain injury: experimental clinical treatment). The RAMPART study — and possibly other NETT studies — involves exception from informed consent (EFIC), a special way of conducting emergency medicine research that enables hyperacute emergency research treatment to proceed even if patients or surrogates are unable to consent at the time. Researchers then work to obtain consent from the patient or family member once the patient arrives at the destination hospital. Those wishing not to participate wear blue bracelets informing paramedics of their choice. RAMPART involves administering study treatment by paramedics on the scene, prior to hospital arrival. Since current regular care for continuous seizures usually involves paramedics and ER physicians giving medication, all eligible patients in status epilepticus at the time of paramedic arrival will be considered for enrollment in RAMPART. As part of the EFIC process for emergency research, Hemphill and Meeker are reaching out to inform the community of this study, which includes making the blue bracelets available to those who do not wish to participate, exempting them from study enrollment. “In order to conduct an EFIC study, the state of California and the federal government require researchers to discuss the study with the community,” Hemphill said. “We care about allowing groups and individuals to ask questions and to find out if there is community support.” Studies that qualify for exception from informed consent involve the following parameters: • Human subjects are in a life-threatening situation • Available treatments are nproven or unsatisfactory • Collection of valid scientific evidence is necessary • Obtaining informed consent is not feasible • Participation in the research holds out the prospect of direct benefit to the study’s subjects • The research could not be practically carried out without the waiver • The investigator has committed to attempt to contact a legally authorized representative for each subject within the hospitalization window • The Institutional Review Board approves informed consent documents and • Additional protection (such as consultation with the community, public disclosure) is provided where research is conducted “We hope the RAMPART study and other research being done through the NETT lead to better treatments for sufferers of status epilepticus and other acute brain and spinal injuries,” Meeker said. “If the coordination of city and county emergency response teams is any indication, many people feel the same way.”