|NIH Outlines Plans for Study of Pediatric Seizures
The scenario unfolds almost every day in the United States. A
crowd gathers at a playground, or perhaps on a soccer field. A
child has fallen to the ground, gripped by a seizure. Usually,
the twitching and jerking stop within a few minutes. If they do
not, the condition becomes status epilepticus, continuous unrelenting
seizures that can lead to brain damage — or even death — if
not treated. An ambulance rushes the child to a nearby hospital
emergency department. There, doctors do their best to administer
life-saving treatment as quickly as possible. Before they can treat
the patient, however, they must choose between one of two drugs
commonly prescribed to treat the condition.
Yet no reliable information exists to determine which of the two
drugs — diazepam and lorazepam — is more effective.
At a briefing at the National Institutes of Health, researchers
today outlined plans for a large-scale national study to determine
which of the two medications is the safest, most effective treatment
for children with status epilepticus. The condition is life-threatening,
and even with the best treatment, is fatal in 4 percent of cases.
The study is the most comprehensive of its kind and 11 hospitals
around the country will participate.
Lorazepam and diazepam are both administered to treat status epilepticus.
Although both medications are regarded as standard treatment, no
large-scale comparison has been conducted to determine which is
the safest, most effective treatment. The Pediatric Seizure Study
will compare the safety and effectiveness of the two medications
in treating status epilepticus in children admitted to hospital
“Currently, the choice of treatment for status epilepticus depends
upon the best judgment of the treating physician,” said Duane Alexander,
M.D., Director of the NIH’s National Institute of Child Health
and Human Development, which is sponsoring the study. “The Pediatric
Seizure Study seeks to provide the most definitive information
possible on which medication offers the greater chance for successful
Status epilepticus affects between 50,000 to 60,000 children and
adults in the United States each year, explained the study’s principal
investigator, James Chamberlain, M.D., Division Chief of Emergency
Medicine at Children's National Medical Center in Washington, D.C.
He added that four to eight children per every 1,000 will experience
status epilepticus before age 15. Status epilepticus may occur
in patients with epilepsy or in 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. Once a drug has been approved by the FDA
for a particular use, physicians may use their best judgment to
prescribe it for other uses, known as “off label” uses, in other
patients whom they believe might benefit.
“We want to hold these two medications to the highest standard
and ensure that children are receiving the most appropriate medication
for their condition,” Dr. Chamberlain said.
To conduct the study, researchers at the 11 participating hospitals
will randomly assign children who are in status epilepticus to
be treated with either lorazepam or diazepam, explained the study’s
co-principal investigator, Jill Baren, M.D., of the Division of
Emergency Medicine, Department of Pediatrics, The Children's Hospital
of Philadelphia, PA. Usually, the choice of which drug to prescribe
would rest with the treating physician. 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 the children will receive each medication.
Dr. Baren added that status epilepticus must be treated within
5 minutes or less of a child’s arrival in an emergency department.
Without prompt treatment, brain injury or death could result. This
means that it will not be possible to obtain permission from a
child’s parent or guardian before enrolling the child in the study.
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 this study, however, it is not possible to explain the study
details and obtain parental permission in advance because of the
urgent need to provide treatment within 5 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; a parent
may not be present when the child is taken to the emergency department.
Children admitted to participating institutions and who meet study
criteria will be automatically enrolled in the study without prior
parental consent. Dr. Baren stressed that this sequence of events
is little different than what would take place in an emergency
department not involved in the study. Under typical circumstances,
the admitting physician would decide on whether the patient would
receive lorazepam or diazepam. In the study, a computer program
will decide which drug the child received. The principle is to
assign the drug without any preference, to avoid any potential
human bias. At the end of the study, roughly equal numbers of children
will have been assigned to receive each drug, and a large enough
number of children will have been studied to allow the researchers
to draw definitive conclusions about each medication.
After the doctor has made sure that the child has received treatment
and has been stabilized, the doctor or a representative from the
study team will contact the parent to let them know that his or
her child has been enrolled in this study. At this time, 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
48 hours later and then 30 days after the child is enrolled to
ask about the child’s condition.
The independent board or research review committee at each hospital
will oversee the study and 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 study will be
“We have consulted a wide range of ethicists, experts and government
officials about this study to ensure that we protect patients’ safety,” Dr.
The researchers have designed a public information campaign to
inform the public about the study in the various communities where
it will be performed, Dr. Baren said. They will hold community
meetings to provide information about the study to all interested
families that might be included in the study. During the meetings
they will answer questions and listen to concerns of community
Dr. Baren stressed the importance of proper research on all emergency
treatments to be sure of their effectiveness. The FDA has emphasized
the need to test all drugs used for children so that those used
are known to be safe and effective.
The NICHD is funding the study in accordance with the Best Pharmaceuticals
for Children Act (BPCA), explained Donald Mattison, M.D., Chief
of the Obstetric and Pediatric Pharmacology Branch. Under the BPCA,
the NIH consults with the U.S. Food and Drug Administration to
determine which approved drugs should be prioritized for further
testing in children. Dr. Mattison added that roughly two-thirds
of drugs prescribed for children have never been specifically tested
In-depth information about the Pediatric Seizure Study is available
from the accompanying set of Questions and Answers, available at http://www.nichd.nih.gov/news/releases/study_pediatric_seizure_QA_052207.cfm.
The National Institutes of Health (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. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.