The ESETT Study Principal Investigator Name

What is Status Epilepticus? Status Epilepticus is seizure activity that does not stop It can cause unconsciousness and jerking activity of the body It is a medical emergency Doctors are planning to conduct research at XX Hospital to find out the best way to treat seizures that have not stopped after a full dose of medicine, like valium, has been given to make them stop.

Who is at risk for status epilepticus? Epilepsy (i.e. seizure disorder) is most common cause Other causes include: o Traumatic brain injury o Brain tumor o Stroke o Alcohol intoxication o Illicit drug use o High fever (in children)

What are the dangers of status epilepticus? o Possible brain damage o Low oxygen o Direct nerve injury o Other tissue damage—muscle and kidney o Death o As many as 17% of patients with SE may die. o The longer the seizure continues the higher chance the patient will die.

How is status epilepticus treated? Patients with status epilepticus are given a drug like valium to make their seizures stop. Seizures that continue after the first dose of treatment is given are known as established status epilepticus, ESE.

How is established status epilepticus (ESE) treated? ESE may be treated with many different drugs. o Some of these drugs include: fosphenytoin, valproic acid and levetiracetam. o Sometimes the doctor will have to completely sedate a patient to stop their seizure using a drug like propofol or phenobarbitol. This may stop the breathing and require life-support. Sometimes two or more drugs may be needed to stop the seizure. It is not known which drug is best for stopping ESE.

A research study designed to find out which of three commonly used drugs best stops established status epilepticus. The ESETT Study

Who will be included in this study? Any patient who is 2 years or older with an active recurrent or ongoing seizure activity lasting longer than 5 minutes AND Has already received an adequate dose of benzodiazepine (like valium) in the past 5-30 minutes to make the seizure stop.

Who cannot be in this study? Any person less than 2 years of age Patients with low or high blood sugar Women known to be pregnant Prisoners or anyone known to be in police custody Patients who have said they do not want to be in the study by a medic alert tag or opt-out bracelet

How will the study work? Every patient coming to the ED who is eligible will be considered. Everyone in this study will be treated with a medication for their seizure. Everyone will get a single dose of one of the three drugs being studied through an intravenous (IV). o The study drugs are: fosphenytoin levetiracetam valproic acid

How will the study drug be chosen? To start 1/3 of patients will randomly get fosphenytoin, 1/3 levetiracetam and 1/3 valproic acid. As the study goes on, a higher proportion of patients will be randomized to the drug or drugs doing better.

What else will happen in the study? A teaspoon of blood may be taken to test for the study medicine in the blood. If the seizure does not stop doctors will follow their normal procedures to try to make it stop. More medicine may be given—this may be one of the study medicines or a different medicine. The study team will monitor the patient while he or she is in the hospital.

What are the possible risks of ESETT? All three drugs are commonly used by doctors to treat seizures. o The risks of the study medicines are the same whether they are given in the study or for treatment of seizures outside of this study. Risks and possible side effects of any of the study medicines include: drowsiness, dizziness, an allergic reaction. In addition: Fosphenytoin may cause low blood pressure, slow heart rate, inflammation of the blood vessels, or skin rash. Levetiracetam may cause behavior changes such as nervousness, confusion, or aggression. Valproic acid may also cause a skin rash and liver or pancreas problems. There is a chance of pain, bruising, swelling, redness, and infection at the IV site. There may be other risks that we are unaware of.

What are the possible benefits of ESETT? Because we do not know which of the study drugs is better, study participants may benefit from receiving a better medicine, but this is not guaranteed. The information that we obtain from this study may help patients in the future. The information may help us to provide more effective drugs in the future for patients with seizures.

How is this study different from most other studies? In other studies, A study investigator explains the study and its risks and benefits. The person is able to ask questions about the study. The person decides to be in the study or not. This process is called INFORMED CONSENT. In this study, Patients with seizures are unconscious and therefore cannot give permission to participate in the study. Also, the study medicine has to be given quickly to stop the seizure activity. Therefore, there is not time to explain the study to family and ask for their consent for the patient to participate.

So how do we do emergency research? Under very specific federal regulations called “Exception From Informed Consent” or “EFIC.” EFIC: allow research to begin without informed consent. These rules were developed by the federal government. They are closely supervised by local research boards.

What kind of studies can be done under EFIC? EFIC can only be used when: The person’s life is at risk, AND The best treatment is not known, AND The study might help the person, AND It is not possible to get permission: o from the person because of his or her medical condition, or o from the person’s family because the medical condition needs to be treated very quickly.

What do we have to do to conduct an EFIC study? Community consultation Public disclosure During the study, a group of experts will watch over the study and stop it if it is clearly helping or hurting people. After the study ends we must share the results with the public.

How does EFIC work in ESETT? All patients having seizures in the ED will immediately be given the usual treatment for seizures– a drug like valium. If the first drug does not stop the seizure, ESETT patients will be treated next with one of the study medications. Patients having seizures will not be awake and will not be able to give consent to the study. There will not be time to get consent from a legally authorized representative (LAR).

What happens next? If the seizure does not stop doctors will follow their normal procedure and give more medication to make it stop. Once the patient wakes up or the LAR is found, he or she will be asked for permission to continue in the study. If the patient continues in the study, he or she will be monitored by the study team until leaving the hospital.

What if a person does not want to be in the study? 1.Wear a bracelet saying “ESETT declined” at all times during the study (about 4 years). 2.Add “ESETT declined” to your medicalert™ tag or system.

Where is ESETT taking place? NETT HubsPECARN Sites ● ● ● ■ ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

What do you think about ESETT? The study has not started yet, so... We want to hear what you think about it. Do you think it is okay to do this study? The study team and the local research review board will consider your opinions before deciding if it is okay to do the study in our community.

Questions? If you have any questions, comments, or concerns about the study, please speak with us now and/or contact us at: Principal Investigator: Name Hospital name Phone Study Coordinator: Name Phone