Study shows autoinjectors offer way to treat prolonged seizures
By by Lance Skelly | Feb. 17, 2012
A quicker and more effective way to stop seizures has been shown in a recently completed nationwide trial, and the study’s findings appear in the Feb. 16, 2012 issue of The New England Journal of Medicine. Drug delivery into muscle using an autoinjector, akin to the EpiPen used to treat serious allergic reactions, may be a more effective way to stop status epilepticus, a prolonged seizure lasting longer than five minutes.
The Department of Emergency Medicine in Emory School of Medicine, in cooperation with Grady EMS, was one of 17 emergency departments in the United States that participated in the clinical study for treatment of patients who are having prolonged epileptic seizures.
Status Epilepticus is a potentially life-threatening emergency that causes 55,000 deaths each year. Anticonvulsant drugs that are FDA cleared for use are only available intravenously (IV).
The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) was designed to study whether giving an intramuscular (IM) formulation of the anti-seizure class of drugs (benzodiazopines) works better and more quickly than when given through an IV (in the vein). The most common benzodiazepine, Lorazepam IV, was compared to Midazolam IM in the RAMPART study. Both drugs are already used by paramedics and doctors across the country to stop seizures, but Midazolam IM has not been FDA cleared and not studied in a large clinical trial.
Starting an IV in a patient experiencing seizures can pose a challenge for paramedics and waste valuable time, according to David Wright, MD, director of emergency neurosciences in the Emory Department of Emergency Medicine. “Imagine trying to thread a needle into a small vein while someone is shaking violently; and then add the twist, turns, and bumps in the back of an ambulance. It is hard to do,” says Wright. “Giving an intramuscular shot is easier, faster, and more reliable, especially in patients having convulsions.”
The researchers sought to determine whether an intramuscular injection, which quickly delivers anticonvulsant medicine into a patient’s thigh muscle, is as safe and effective as giving medicine directly into a vein. The study, which was carried out by paramedics, compared how well delivery by each method stopped patients’ seizures by the time the ambulance arrived at the emergency department.
“Status Epilepticus is a true emergency associated with significant disability and even death, says Wright. “It is estimated that there are between 120,000 and 200,000 cases of Status Epilepticus in this country each year resulting in as many as 55,000 deaths. Complications of prolonged seizures may include trouble breathing, abnormal heart rhythm, altered level of consciousness and injury to the brain or nervous system.”
RAMPART is the first randomized clinical trial to investigate whether intramuscular delivery of midazolam is as effective as IV lorazepam, the current standard of care. The trial started in 2009 and completed enrollment in June, 2011. 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.
Patients who suffer a head injury have a 50 percent chance of developing epilepsy within two years, Wright said. More than three million people in the United States have some form of epilepsy, which can result in severe physical convulsions, loss of consciousness, or short-term memory loss.
The investigators compared two medicines known to be effective in controlling seizures, midazolam and lorazepam. Both are benzodiazepines, a class of sedating anticonvulsant drugs. Midazolam was a candidate for injection because it is rapidly absorbed from muscle. But lorazepam must be given by IV. 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. Among those admitted, both groups had similarly low rates of recurrent seizures.
Another special aspect of the study was that it was conducted under exception from informed consent (EFIC) for emergency research. This is a federal regulation to protect patients who are involved in research when consent is not possible because of their medical condition. Community consultation is held in advance of the study to raise awareness, ensure transparency, and get input from local residents. In addition, public announcements and disclosure of the study are performed prior to the start of the study.
“Under normal circumstances and traditional guidelines, researchers will ask for permission before a person can or does participate in a clinical study. And in the event a patient is unconscious - due to a seizure or another medical condition - researchers will ask for permission from the person’s legally authorized representative. But since convulsive seizures must be treated very quickly – often even before a patient is placed in an ambulance for transport to a hospital - there is usually not enough time to talk to a legal guardian or family member about the study,” says Wright. The EFIC process was approved by the FDA and local institutional review board (IRB).