March 19, 2008
Study will be the first to determine which drug is more effective
Researchers at the University of Maryland Hospital for Children are participating in a large-scale national study to determine which of two commonly used medications is the safest, most effective treatment for children with status epilepticus, a condition marked by a continuous prolonged seizure. The study is the most comprehensive of its kind with participation by 10 hospitals around the country.
The two drugs, lorazepam and diazepam, are both regularly administered to treat status epilepticus. The Pediatric Seizure Study, sponsored by the National Institutes of Health with the support of the Health Resources and Services Administration, will compare the safety and effectiveness of the two medications in treating status epilepticus in children admitted to hospital emergency departments.
"Currently, the choice of treatment for status epilepticus depends upon the best judgment of the treating physician," said Richard Lichenstein, M.D., principal investigator for the study at the University of Maryland Hospital for Children and an associate professor of pediatrics at the University of Maryland School of Medicine. "The Pediatric Seizure Study seeks to provide the most definitive information possible on which medication offers the greater chance for safe, successful treatment."
Status epilepticus affects between 50,000 to 60,000 children and adults in the United States each year. Four to eight children per every 1,000 will experience status epilepticus before age 15. Status epilepticus may occur in people with epilepsy or in those patients without epilepsy who experience a seizure due to a high fever, low blood sugar, an infection of the central nervous system, or a head injury. Children who have no apparent risk factors may also develop status epilepticus.
Diazepam, more commonly known as Valium, has been approved by the U.S. Food and Drug Administration for use in adults and children. Lorazepam, marketed under the name Ativan, is only approved by the FDA to treat seizures in adult patients but is widely prescribed off label for children.
To conduct the study, researchers at the University of Maryland Hospital for Children will randomly assign children who are in status epilepticus to be treated with either lorazepam or diazepam.
“Usually, the choice of which drug to prescribe would rest with the treating physician,” says Dr. Lichenstein. “During the study, however, the medication will be assigned randomly by a computer, to eliminate any potential human bias in assigning the medication. A roughly equal number of children will receive each medication.”
Normally, researchers first ask the parent or guardian for permission to enroll a child in a study, explain the details and procedures of the study, its potential risks and benefits, and alternatives, and enroll the child only after the parent or guardian agrees. For the Pediatric Seizure Study, however, it will not be possible to explain the study details and obtain parental permission in advance because of the urgent need to provide treatment within five minutes of the child's arrival in the emergency department. Moreover, status epilepticus may occur when a child is away from his or her parents and a parent may not be present when the child is taken to the emergency department.
Children seen in the pediatric emergency department at the University of Maryland Hospital for Children who meet study criteria will be automatically enrolled in the study without prior parental consent. Dr. Lichenstein stressed that this sequence of events is no different from what would take place in an emergency department not involved in the study. “Under typical circumstances, the attending physician would decide on whether the patient would receive lorazepam or diazepam,” he says. “In the study, a computer program will decide which drug the child receives. At the end of the study, a large enough number of children will have been enrolled to allow us to draw definitive conclusions about each medication.”
After a child has received treatment and has been stabilized, the doctor or a representative from the study team will contact the parent to let him or her know that the child has been enrolled in the study. Then, the details of the study will be explained to the parent, and the parent can choose to allow the child to continue in the study or can withdraw the child from the study.
If the parent agrees to continue, small blood samples will be taken from the child and the parent will be interviewed by phone 30 days after the child is enrolled to ask about the child's condition.
“We have designed a public information campaign so that people in our West Baltimore neighborhood will know that the University of Maryland Hospital for Children is participating in this national study,” said Dr. Lichenstein. “We will hold community meetings to provide information about the study to all interested families who might be included in the study. These meetings will be an opportunity for parents and other interested parties to ask questions and hear directly from myself and other members of the study team.”
The pediatric seizure study has been reviewed and approved by the Institutional Review Board at the University of Maryland School of Medicine to ensure that all procedures comply with ethics and safety standards. Other independent reviewers will look for overall trends in study data. If it becomes clear that one drug is more effective at treating seizures, the national study will be ended early.
“Proper research on all emergency treatments for children is vital to be sure of their effectiveness,” says Dr. Lichenstein. “The FDA has emphasized the need to test all drugs used for children so that those used are known to be safe and effective. This study is being conducted under the highest ethical standards and the results we get will have important implications on how we treat seizures in children.”
A web site and national hotline have been created to provide further detail about the study and the option to contact a specific hospital: http://www.dcchildrens.com/seizurestudy/ and 1-866-377-8557.