1. Principal Investigator
The ESETT Study
Principal Investigator
Name

2. Emergency Department Research
A research study is a way for doctors to find new information about a disease, or best way to treat a condition
Research helps doctors develop the best treatment for patients in all areas of medicine, including emergency medicine
Conducting research in an emergency department can be difficult because the patient can be very sick

3. What is a seizure?
Seizures are a common childhood illness. A seizure causes jerking activity of the body and can cause unconsciousness
Epilepsy (i.e. seizure disorder) is the most common cause of a seizures
Other causes include:
Brain injury or tumor
Stroke
Alcohol intoxication or drug use
High fever (in children)

4. 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!
Patients with status epilepticus are given medicine, like valium, to make their seizures stop.

5. What are the dangers of status epilepticus?
Possible brain damage
Low oxygen
Direct nerve injury
Other tissue damage—muscle and kidney
Death
The longer a seizure continues the greater the chance the patient could die from their seizure.

6. What is Established Status Epilepticus (ESE)?
Seizures that continue after treatment with medicines like valium are known as Established Status Epilepticus, ESE.
ESE may be treated with many different medicines
Sometimes two or more drugs may be needed to stop the seizure.
We do not know which drug is best at stopping ESE.

7. The ESETT Study
Doctors at XXX are joining 39 other hospitals across the country to conduct a study to find out the best way to treat Established Status Epilepticus (ESE)

8. ESETT
ESETT is a research study designed to find out which of three commonly used drugs is best to stop established status epilepticus.
The medicines being studied are:
Fosphenytoin (Cerebyx)
Valproic acid (Depakote)
Levetiracetam (Keppra)

9. 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.

10. 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

11. How will the study work?
Every patient coming to the ED who is eligible will be considered for the study.
Everyone in this study will be treated with a medication for their seizure.
Patients who are enrolled in the study will receive a single dose of one of the three drugs being studied through a needle in the vein (IV).

12. 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.
Notes to help study teams talk about how and what “adapted randomization design” is in lay terms.
In the beginning everyone has the same equal chance of receiving any of the study drugs available.
As the study goes along if one study drug seems to be helping to stop a seizure faster, the chances of receiving that study drug will go up.
The doctors will not know which drug may be doing better, worse or the same until the study is over.
Once there is enough proof that one drug is indeed superior or on the other side inferior the study will be stopped.

13. 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.

14. What are the possible risks of ESETT?
There are risks involved in participating in research. Risks and possible side effects of any of the study medicines include: drowsiness, dizziness, and an allergic reaction.
Additionally:
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 may be other risks that we are unaware of.
Prolonged seizures are associated with substantial medical risks.  
The study medicines, fosphenytoin, levetiracetam and valproic acid, are all anti-convulsants, but they work in different ways, and have different risks.
Levetiracetam and valproic acid are investigational drugs.
These drugs have been approved by the Food and Drug Administration (FDA) to prevent seizures in adults and children, but not to stop long lasting seizures as in established status epilepticus.
Doctors have used both of these drugs “off-label” to safely stop these seizures for years.
Fosphenytoin
has been approved by the FDA to stop long seizures in adults, but not children.
Doctors have also used fosphenytoin to safely stop seizures in children for years.

15. All three drugs are commonly used by doctors to treat seizures
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.

16. 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.
The information we collect may help us to provide more effective drugs in the future for patients with seizures.

17. 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 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 in advance.

18. Rules for Emergency Research
With Emergency Research like ESETT, it’s not possible to get informed consent before treating the patient. The federal government allow for this kind of research following procedures called:
Exception From Informed Consent or “EFIC”
EFIC allow research to begin without informed consent.
The researchers who perform research in emergency settings are carefully supervised:
Locally by Institutional Review Boards, also called IRBs, which work to protect the safety of patients participating in research.
And federally there is oversight by the National Institutes of Health, the Food and Drug Administration, and the Office of Human Research Protections.

19. 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:
from the person because of his or her medical condition, or
from the person’s family because the medical condition needs to be treated very quickly.

20. The Emergency Research Procedures for 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 able to give consent
They are not awake
They need emergency treatment and there is not time to consent a legal guardian or parent.

21. What happens next?
If the seizure does not stop doctors will follow their normal procedure and give more medication to make the seizure 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.
Kid alternative:
Once the patient is treated and there is time to talk with a parent or guardian, he or she will be asked for permission for their child to continue in the study.
If the patent gives permission, the study team will monitor the patient until he/she leaves the hospital.
When the patient is able, he or she will also be told about the study.

22. What if a person does not want to be in the study?
Procedures are in place to identify those who do not want to participate. As a part of these procedures, a person may be asked to:
Wear medical jewelry, like a bracelet, with the message “ESETT declined” at all times during the study .
This template represents the two opt-out mechanisms available and approved by ESETT Leadership.
However, 21 CFR does not require an opt-out mechanism be made available.
This slide should be tailored to acknowledge the opt-out mechanism(s) being offered locally.

23. 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.
Click here (on the link below) to complete the survey.
<<insert link to survey>>

24. Where is ESETT Planning to take place?
NETT Hubs
PECARN Sites ● ■