Feb. 16, 2012
CHARLESTON -- Drug delivery into muscle using an autoinjector, akin to the EpiPen used to treat serious allergic reactions, is faster and may be effective at stopping seizures lasting longer than five minutes, according to a study sponsored by the National Institutes of Health (NIH). The study appears in the Feb. 16, 2012 issue of The New England Journal of Medicine.
The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) study was conducted through the National Institute of Neurological Disorders and Strokeís (NINDS) Neurological Emergencies Treatment Trials (NETT) network. MUSCís Data Coordination Unit (DCU), in the division of Biostatistics and Epidemiology, is the NETT statistical and data management center. The University of Michigan in Ann Arbor served as the NETT clinical coordinating center. Additional funding was provided by the NIH Countermeasures Against Chemical Threats (NIH CounterACT) program and the Biomedical Advanced Research and Development Authority (BARDA). The Department of Defenseís Chemical Biological Medical Systems (CBMS) Joint Project Management Office provided the autoinjectors for the trial under a memorandum of agreement with NINDS.
RAMPART involved more than 79 hospitals, 33 emergency medical services agencies, more than 4,000 paramedics and 893 patients ranging in age from several months old to 103.
At MUSC, the DCU played a vital role in the statistics and data management for the RAMPART trial. "We collaborated with an excellent clinical team from around the country that brought together expertise in emergency medicine, neurology and the pre-hospital setting," said Valerie Durkalski, Ph.D., RAMPART lead biostatistician and NETT statistical and data management center co-PI. "It takes several years for a study of this magnitude to get to this stage, and we are very excited to share the results that could potentially change clinical practice for the pre-hospital treatment of status epilepticus."
Status epilepticus (seizures lasting longer than five minutes) is a potentially life-threatening emergency that causes 55,000 deaths each year. Anticonvulsant drugs are typically delivered intravenously (IV) as a first-line treatment by paramedics in the field; however, trial clinical consultant Ed Jauch, M.D., MUSC Division of Emergency Medicine interim director and Department of Medicine associate vice chair for research, notes a challenge with this method.
"Starting an IV in the back of an ambulance while someone is having a seizure is very difficult and it wastes precious time. Time is brain, and the network of centers involved in this study sought to engage EMS providers to see if there was a better way to deliver similar medications. The results have immediate civilian and military implications," he said.
The study compared how well delivery by each method stopped patientsí seizures by the time the ambulance arrived at the emergency department. Investigators compared two medicines known to be effective in controlling seizures, midazolam and lorazepam. The study found that 73 percent of patients in the group receiving midazolam were seizure-free upon arrival at the hospital, compared to 63 percent of patients who received IV treatment with lorazepam. Patients treated with midazolam were also less likely to require hospitalization than those receiving IV lorazepam. Both groups had similarly low rates of recurrent seizures.
Walter Koroshetz, M.D., NINDS deputy director said, "Patients with status epilepticus can suffer severe consequences if seizures are not stopped quickly. This study establishes that rapid intramuscular injection of an anticonvulsant drug is safe and effective."
While autoinjectors for treatment of seizures might take some time to reach epilepsy patients and their family members, Jauch predicted a short road to widespread use.
"The findings indicate, in a worst case scenario, that autoinjectors provide the ability to quickly treat hundreds of soldiers on the battlefield or large segments of the population in the event of biochemical attacks. Stopping seizures as quickly as possible is paramount in all emergency situations, but especially in a mass casualty situation, where there wonít be enough people to start all the IVs that would be needed. This method is more mobile, itís faster, itís easier, and itís effective."
NIH CounterACT, BARDA and CBMS are responsible for enhancing the U.S. governmentís development of medical countermeasures to natural and intentional public health threats (please see full statement below on CBMS). The chemical defense community has a longstanding interest in research on the rapid treatment of nerve agent-induced seizures. As the RAMPART study was being planned, investigators learned that the departments of Defense and Health and Human Services were already working with a midazolam autoinjector and the study was an opportunity to confirm its effectiveness in patients with seizures. ### About the National Institutes of Health (NIH) NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov. About MUSC Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents, and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $1.7 billion. MUSC operates a 700-bed medical center, which includes a nationally recognized Children's Hospital, the Ashley River Tower (cardiovascular, digestive disease, neuroscience/stroke and surgical oncology), and a leading Institute of Psychiatry. For more information on academic information or clinical services, visit www.musc.edu. For more information on hospital patient services, visit www.muschealth.com.
Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents, and has nearly 11,000 employees, including 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $1.7 billion. MUSC operates a 750-bed medical center, which includes a nationally recognized Children's Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), and a leading Institute of Psychiatry. For more information on academic information or clinical services, visit www.musc.edu or www.muschealth.com.