May 23, 2007
The Pediatric Seizure Study is a research study designed to find out which of two commonly prescribed medications, Diazepam or Lorazepam, is best for treating children with status epilepticus—continuous, unrelenting seizures.
The condition must be treated within minutes after a child comes to an emergency room, to minimize the chances of brain damage or death. In some communities the treatment is given even before the child enters the emergency room. Status epilepticus is life threatening, and even with the best treatment, is fatal in 4 percent of childhood cases.
Currently, Diazepam and Lorazepam are the standard medications given to children with status epilepticus when they enter the emergency department. Both medications are considered safe and effective, although only Diazepam has been approved specifically for use in children. To date, however, neither medication has been proven more effective than the other for treating children with status epilepticus.
This study will follow children admitted to emergency departments in a number of communities to determine which treatment is more effective.
The National Institute of Child Health and Human Development, part of the National Institutes of Health, is sponsoring the study as part of the Best Pharmaceuticals for Children Act of 2002. Under the BPCA, the NIH consults with the U.S. Food and Drug Administration to determine which drugs should undergo further testing in children.
Status epilepticus may occur in anyone who has a seizure disorder, which is often called epilepsy. The condition often results from failure to take medications that are used to prevent seizures. It may also occur in response to such conditions as meningitis (infection of the fluid around the brain), brain tumor, head injury, extremely high fever, or low blood sugar levels.
Both Diazepam and Lorazepam are commonly used by doctors to treat seizures in children. Diazepam has been approved by the Food and Drug Administration for use in both adults and children. Lorazepam has been approved only for adult use but for years it has been prescribed off label to treat children. Once the FDA has approved a drug for a particular use, doctors can use their best judgment to prescribe it for other uses, known as “off label” uses, for a patient they believe would benefit from it. Doctors commonly prescribe drugs tested only in adults to children in this fashion because many drugs have not undergone pediatric testing.
Lorazepam and Diazepam are both considered to be effective in treating seizures, although only Diazepam has been approved specifically for use in children. At the end of this study, doctors hope to know which medication is better for treating children’s seizures.
A child admitted to an emergency department at one of the study sites will be examined immediately by a physician and nurse, who will determine if the child is an appropriate candidate for the study.
If the child is an appropriate candidate for the study, he or she will be randomly assigned to receive either Diazepam or Lorazepam to treat the status epilepticus. The medical team will continue treatment until the child is stable. After the child has stabilized, the medical team will explain the purpose of the study to a parent or guardian. At this point, the researchers will let the parent or guardian know that they could decide to discontinue the child’s participation in the study. Continued participation involves additional monitoring of the child including additional blood sampling as well as the parent’s responding to follow up questions by telephone 48 hours and 30 days later.
Because children who are seizing must be treated immediately, researchers can not rely on the usual procedures for enrolling a child in a study. Normally, researchers ask permission from a parent or guardian before enrolling a child in a research study. The researchers contact the parent or guardian, and then explain the details and procedures of the study, as well as its potential risks and benefits. The child is enrolled only if the parent or guardian gives consent.
For the Pediatric Seizure Study, however, it is not possible to obtain parental consent in advance. Anti-seizure medication must be given within five minutes of a child’s arrival in the emergency department. This means there may not be enough time to talk to a child’s parent or guardian about the study. For this reason, and because it is not always possible to identify ahead of time which children will develop status epilepticus, a child who meets study criteria will automatically be enrolled in the study without parental permission, unless a parent notifies the hospital in advance that they do not want the child to be part of the study.
After a child who has been enrolled in the study has been stabilized, parents will be asked if they wish the child to continue participating in the study. There will be no difference in the quality of the subsequent medical care provided to the child, whether or not he or she continues to participate. However, children who participate in the study will receive additional medical monitoring beyond that done during regular medical care.
After the doctor has made sure that the child has been stabilized medically, the doctor or a representative from the study team will contact the parent to let them know that his/her child has been enrolled in this study. At this time, the parent will be given all of the details about the study and can choose to continue or stop the child’s participation.
The study will be stopped as soon as researchers know which medication offers the best treatment.
To prevent brain damage or death, status epilepticus must be treated immediately. The need to begin treatment right away means that there isn’t enough time to explain the study and ask parents or caregivers for their permission.
Study investigators are taking several steps to inform the communities in each of the areas where the study will take place. The idea is to provide as much general awareness as possible about the study since the normal individual consent process will not be possible. The researchers will accomplish this through meetings with community groups in their areas, through contact with the news media as well as through other kinds of outreach activities.
Parents/guardians may decline to have their child take part in the study, either before the child experiences status epilepticus or even during an episode of status epilepticus when they are present with their child in the emergency department.
Families will be given every opportunity to decline to participate before a medical emergency arises. If a child resides in a study area and his or her parents do not want the child to participate, the parents may contact the center in their area to make their wishes known. (Participating centers are listed at the end of this document.) Children who decline to participate in the study will still receive the best medical care for their seizure.
Participating study sites vary as to when they will begin the study and when they will begin informing their communities that the study will take place. Even though all sites are currently undergoing a thorough review process before beginning, some sites will begin within the next few weeks, whereas other sites are not expected to begin for several months.
This varies with the individual sites and will depend on when the study begins at each site. Once a study site is approved, it will hold community meetings, outreach activities, and post other notices about when the study is ready to begin in their areas. At that time, there will be procedures in place for parents and guardians to contact their local sites if they do not want their child to participate. Parents and guardians who are interested in finding out when their local site may be conducting community outreach or when they may be starting the study should contact the seizure study coordinator or investigator in the emergency department of the participating site in their area.
Children who participate in the study will receive additional medical monitoring beyond that done during regular medical care. Information gained from the study’s conduct may help other children in the future by improving the treatment for status epilepticus.
Participation in the study poses no risks beyond those posed by standard treatment for status epilepticus. Seizures can be life threatening and occasionally fatal, despite doctors’ best efforts to treat them.
Both medications in the study are already used to treat children with seizures. Lorazepam and Diazepam may cause such side effects as respiratory depression (a slowed rate of breathing), sleepiness, muscle cramps, anxiety, dizziness, and visual hallucinations.
Study participation also includes drawing small samples of blood from the child, but would not be done without parental permission. Parents or guardians of children enrolled in the study will be interviewed 48 hours after the child is enrolled and then again in 30 days. Parents or guardians would not be contacted without their advance permission.
As part of this study, parents would not be required to return to the hospital for any additional visits—the last telephone interview would end the child’s participation in this study.
Study investigators will hold community meetings and conduct other outreach activities to provide information about the study to groups living in the study areas. At the meetings, the study investigators will answer questions and listen to comments and concerns of members of the communities where the study is taking place.
The Pediatric Seizure Study will be conducted by the following 11 children’s hospitals and universities:
The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Web site at http://www.nichd.nih.gov/.
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 http://www.nih.gov.