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National trial shows autoinjectors faster, more effective than IV lines in stopping seizures

2012-02-16
(Press-News.org) CINCINNATI -- As part of the first national, randomized clinical trial to study two methods of drug delivery for seizing patients, researchers have shown that using an auto-injector, similar to an EpiPen, to deliver anticonvulsant medication stops prolonged seizures more quickly and effectively than drug delivery through an IV line.

The research, which will be published in the Feb. 16 edition of the New England Journal of Medicine, was conducted as part of the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), which included University of Cincinnati (UC) researchers and local paramedics as part of a nationwide effort studying status epilepticus, or prolonged seizure lasting more than five minutes.

Nationwide, 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 age 103. The study was conducted through the Neurological Emergencies Treatment Trials (NETT) network and sponsored by the National Institutes of Health's National Institute of Neurological Disorders and Stroke (NINDS), which formed NETT to link 17 major research hospitals to conduct clinical trials on acute conditions of the brain.

Cincinnati had the second highest participation site in the nation, with 133 patients treated in the study by participating fire/EMS agencies across the region. In Ohio, UC was supported by Cincinnati, Blue Ash, Forest Park and Green Township fire departments and, in Kentucky, by Florence and Independence fire departments. Leading the study in Cincinnati was Arthur Pancioli, MD, professor and Richard C. Levy Chair for Emergency Medicine at UC.

"Prolonged seizures are dangerous, and may be life threatening," says Pancioli. "As with many neurological emergencies, treating status epilepticus as rapidly as possible can significantly improve a patient's outcome. We now know that using midazolam via an autoinjector, which is easier to administer to a seizing patient, is just as good, if not better, than our current practice which requires starting an IV line."

RAMPART focused on two anticonvulsant medications known to be effective in controlling seizures: midazolam, able to be rapidly absorbed from muscle, and lorazepam, the current standard of care, which must be delivered by IV.

Carried out by paramedics, the study sought to compare how well delivery by each method stopped patients' seizures by the time the ambulance arrived at the emergency department. Researchers found that 73 percent of patients 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. Among those admitted, both groups had similarly low rates of recurrent seizures.

Starting enrollment in 2009 and completing in June 2011, RAMPART was a unique form of clinical trial, eligible under the Food and Drug Administration requirement of "exception from informed consent." The federal regulation was created to protect patients who are involved in research when consent is not possible because of their medical condition. Researchers held community consultation and public awareness events before RAMPART's launch to raise awareness and get feedback from residents.

"This trial is significant, not only for its findings, but also for the research methods involved," says Pancioli. "We would like to thank the dedicated EMS personnel for their work on the trial and also our community for their trust in allowing us to perform this study. Without this type of research, critical opportunities to help patients with neurological emergencies would be lost."

"In our region, many fire departments and EMS agencies have been using midazolam to treat seizures for several years, and this trial affirms the safety and effectiveness that we have seen," says Jason McMullan, MD, RAMPART co-investigator and assistant professor of clinical emergency medicine at UC.

"The use of the auto-injectors could further improve the excellent care our paramedics provide to their patients every day," he says. "While the auto-injectors are not yet commercially availability, this trial provides an opportunity to change the way that paramedics everywhere deliver time critical treatment for status epilepticus and improve the potential outcomes for our patients."

###McMullan is also part of the medical direction team for the Cincinnati and Forest Park fire departments.

UC also partnered with Cincinnati Children's Hospital Medical Center to manage pediatric patients enrolled in RAMPART. RAMPART was funded through the National Institutes of Health via NINDS. 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 Defense's Chemical Biological Medical Systems (CBMS) Joint Project Management Office provided the auto-injectors for the trial under a Memorandum of Agreement with NINDS.


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[Press-News.org] National trial shows autoinjectors faster, more effective than IV lines in stopping seizures