ESETT Tips University of Michigan Hospital RC phone: Lead RC

Transcription

1 ESETT Tips University of Michigan Hospital RC phone: Lead RC Clinical Team Training: Initial and Ongoing Nursing Staff o During study startup, we attended nursing shift change meetings as often as we could over a few week period of time to train on the study. We go over inclusion/exclusion, step-by-step poster, workflow of who is responsible for identifying an ESETT patient and how to contact RCs, drug infusion, and max dose drug infusion. We print materials on these topics to pass out during the meetings. Refer to the Nursing Guide to ESETT for RC use on page 4. Max dose drug infusion needed more attention in nurse training. There were concerns about the patient receiving full dose when the line starts to run dry since the drug vials are only 100 ml and max dose is 90 ml. Refer to the Drug Infusion Guide and Procedure Demonstration for Max Dose on pages 6 and 13. If we attend a meeting where most nurses have heard our ESETT training spiel, we will then quiz them on the basics. Once we feel most nurses understand the procedures, we plan to visit shift change meetings during the first week of each month to satisfy the ongoing training requirement mentioned in section 5 of the MOP. o RCs and PI also attended prescheduled charge nurse monthly meetings. Pharmacy o RCs and PI attended prescheduled pharmacy monthly meetings. Pharmacy is a useful contact for us because the staff is much smaller than the nursing staff and is involved in all medication dispensing. Therefore, they are usually our first go-to when a potential ESETT patient presents to the ED. Social Work o RCs and PI attended prescheduled social work monthly meetings. Since this is an EFIC trial, an LAR may be involved, and parents often stay in the resus bay, we wanted to ensure social work was familiar with the study in case any questions or issues arise. Social work is prepared for these Last Updated: 04/05/2016 1

2 scenarios until an RC arrives. We have provided them with the Social Work Guide to ESETT and brochures. Refer to the Social Work Guide to ESETT on page 14. Attending Physicians o Attending physician education was managed by our site PI through faculty meetings and s. Supplemental Materials o RC contact information is available at the charge nurse desks, on the step-by-step posters, usenext boxes, and pocket cards (explained below). This is for easy and quick accessibility when a patient comes in (we do 24/7 on-call). We use Google voice, but other sites use paid services with a higher hit rate (Google Voice sometimes fails to deliver messages to some people on the forwarding list). o Pocket cards were made for attending physicians, RCs, nursing staff, and pharmacy to keep in ID badges. These include the PI hotline and RC on-call contact numbers, and brief inclusion/exclusion criteria for easy reference. Refer to the pocket cards for RCs/attending physicians and nursing staff on pages 15 and 17 (pharmacy pocket cards are similar as that of RCs but include a chart explanation of adequate dose of benzos). Screening When a potential patient first presents to the ED, review of inclusion/exclusion with pharmacy and/or nursing staff is a good idea. This is beneficial for the following reasons: Clinical team would be ready if the patient becomes eligible during the ED visit and this serves as a recap of general education. o Carrying the ESETT enrollment folder when a potential patient presents to the ED serves as a subtle reminder of the study as well. We have a BPA (automatic notification) set up to page us when a patient presents to the ED who is roomed in a resus bay with a chief complaint of seizures and is 2 yo. We do not depend on this for screening and it does not replace the current method of MD, RN, pharmacy being aware of the study, but this gives us real-time notification when an RC is in the office. Enrollment If sites do not have the PAD, be sure to set an alarm, such as on your phone, for the 20 and 60 minute assessments so as not to forget. o Have clinical team conduct the 20 and 60 minute assessments and be sure patient s status at these times is noted in the patient s chart. Last Updated: 04/05/2016 2

3 If you are in the resus bay before drug infusion, be sure to note the exact time when study drug infusion starts, and confirm the time of benzo administration. With so much happening all at once, the administration times of one or both are sometimes charted a few minutes off. o If you know for a fact when study drug infusion started and this does not correspond with what is noted in the chart, look into getting this timestamp corrected in the EMR. Consenting In the event of no LAR present, utilize social work to inquire into the status of an LAR and get their feedback to determine if the adult patient is cognitively able to understand the consent process. Since this is an EFIC trial, wording is important. Our Consent Introduction and Talking Points are included in our RC Enrollment Guide that we follow during an enrollment. Refer to the RC Enrollment Guide on page 19. o Our site PIs usually try to do the Consent Introduction and then RCs will go through the consent form. We feel this is best for the patient, especially if we are talking to the parents of a child, to first learn about the enrollment and the study from the PI. If no PI available in person, be sure they are available by phone when needed, RCs then follow these tips: Don t be too ambiguous; make sure the parent or patient knows they were enrolled into the study not that they might be in the future. Stress that the patient would have received one of these three drugs anyway via doctor s preference per standard care. There is no good scientific evidence to suggest one is better than the other and there is no universal agreement among doctors about which is best. Avoid the verbiage FDA approved since levetiracetam and valproic acid have not yet been approved to stop long seizures and fosphenytoin has not been approved to stop seizures in children. We say commonly used medications that doctors use. Consenting should take place after things have calmed down. This varies among sites, some wait until after the 60 minute time point, we approach for consent as soon as it is appropriate. If no PI is present for the consenting process, we have found that dual RC consenting is helpful. One RC serves as the main consenter while the other can assist by observing how the parent or patient is reacting, offering additional information, etc. Last Updated: 04/05/2016 3

4 ESETT HUM Study Title: Established Status Epilepticus Treatment Trial (ESETT) A multicenter, randomized, blinded, comparative effectiveness study of fosphenytoin, valproic acid, or levetiracetam in the emergency department treatment of patients with benzodiazepine-refractory status epilepticus. PI PEDS: A. Rogers, MD PI Adult: R. Silbergleit, MD Materials Study Purpose Inclusion/ Exclusion Nursing Guide to ESETT (RC Use Only not a handout) Procedure Demonstration for Max Dose. Access here. Step-by-step poster print out. Access here. Inclusion/Exclusion card and dosing chart. Access here. Pocket cards. Front. Back. ESETT box appropriate to location Opt-out bracelet Established Status Epilepticus Treatment Trial or ESETT looks at which of these three medications as a second line convulsant: fosphenytoin (also called Cerebyx, similar to Dilantin), levetiracetam (also called Keppra) and valproic acid (also called Depacon or Depakote) is most effective in patients who have seizures that continue despite initial emergency treatments. Patients will be randomized to one of these three drugs. This is a double-blind study. This is an Exception from Informed Consent study, so subjects will be enrolled before they are consented to be in the study. Once things have settled study team will approach LAR to get consent. Social Work will also be aware of the study and can assist when needed. 1.) Patient witnessed to seize for greater than 5 minute duration prior to treatment with study drug 2.) Patient received adequate dose of benzodiazepines. The last dose of benzo was administered in the 5-30 minutes prior to study drug administration, 3.) Continued or recurring seizure in ED 4.) Age 2 years or older. Exclusion Criteria: 1.) Known pregnancy, severe metabolic/liver/renal disease 2.) Known allergy or contraindication to: phenytoin (Dilantin), fosphenytoin (Cerebyx), levetiracetam (Keppra), or valproic acid (Depakote) 3.) For this episode of status epilepticus already given intravenous 2 nd line anticonvulsant or non-benzo sedatives with anticonvulsant properties (propofol, atomidate, ketamine, etc) or endotracheally intubated 4.) Status epilepticus thought to be caused by: hypoglycemia <50mg/dL; hyperglycemia >400mg/dL; acute traumatic brain injury; cardiac arrest/post anoxia 5.) Prisoner 6.) Opt-out identification declining ESETT Procedure Everyone is responsible for identifying an ESETT patient Ask the physician if patient is ESETT eligible Follow step-by-step poster ESETT box will be kept at recording nursing desk

5 ESETT HUM Study Title: Established Status Epilepticus Treatment Trial (ESETT) A multicenter, randomized, blinded, comparative effectiveness study of fosphenytoin, valproic acid, or levetiracetam in the emergency department treatment of patients with benzodiazepine-refractory status epilepticus. PI PEDS: A. Rogers, MD PI Adult: R. Silbergleit, MD o Pharmacy will then collect box if RC has not arrived in time. CALL THE STUDY TEAM AT !!! o This number will be located with the step-by-step poster, on your pocket cards, and ESETT box. If there has been no word from study team that they are on their way, you are to call this number again. Don t Forget! Explain dose administration at max dose. Watch the training video located on your pocket cards. o Keep your pocket cards on you at all times. o Explain pocket cards. Show opt-out bracelet. o Patients can also opt out of ESETT with their medical alert bracelets. Take Home Message FAQs If an ESETT pt appears to be eligible, ask physician if pt is ESETT eligible. Q. What entails adequate dose of benzos? A. Subject received adequate cumulative dose(s) of benzodiazepines (may be administered in two or more divided doses): For all adults, and children 32 kg, adequate doses are at least: diazepam 10 mg IV or PR or lorazepam 4 mg IV or midazolam 10 mg IV or IM For children < 32 kg, adequate doses are at least: diazepam 0.3 mg/kg IV or PR or lorazepam 0.1 mg/kg IV or midazolam 0.3mg/kg IM - or 0.2 mg/kg IV Q. Does the exclusion criterion metabolic disease refer to patients with diabetes? A. No. Metabolic disease does not refer to either diabetes nor to the socalled pre-diabetic metabolic syndrome. Rather, the term metabolic disease is an exclusion based upon a warning on the FDA label for VPA referring to certain rare inborn errors of metabolism in children less than 2 years old.

6 HUM Last Updated: Drug Infusion Guide

7 Step 1: Preparation by ED Pharmacist If dose volume is 60mL: Obtain appropriate size syringe depending on dosing volume e.g., doses between 9-20mL, use 20mL syringe; doses between 21-30mL, use 30mL syringe; doses between 31 to 60mL, use 60mL syringe Attach tubing Draw-up volume of dose based on weight (from dosing chart) plus at least (more is fine) 1.1mL (fill volume of tubing = 1.1mL) Prime line with drug by adjusting volume in syringe to dose volume (from the chart) This should result in a syringe that reflects the correct dose volume and a primed line If dose volume is >60mL: Pharmacy to dispense full vials ED RN will attach tubing (fill volume of this tubing is approximately 6mL)

8 Nursing Staff Step 2: If Dose Volume is 60mL (Patient weight <60Kg) via Syringe Infuse IV over 10 minutes Program infusion pump to deliver the volume/rate indicated on the dose administration chart The volume and rate should be confirmed by a second nurse Do not flush Alaris tubing after dose is infused Disconnect line from T-Connector and discard before administering anything else to patient. Keep vial for study team Note: T-Connector does not need to be disconnected. The 0.55mL of fluid in T-Connector is okay.

9 Nursing Staff Step 2: If Dose Volume is >60mL (Patient weight 60Kg) via Drug Vial Open fill chamber vent for glass vial Spike vial, prime line with drug Prime line upside down as not to waste any drug Connect study drug vial as primary infusion line Note: Patient already have a line? Connect ESETT drug as primary line so patient gets drug as soon as infusion starts!

10 Nursing Staff Step 3: If Dose Volume is >60mL (Patient weight 60Kg) via Drug Vial Program pump to deliver the volume/rate indicated on the dose administration chart Second nurse confirm volume and rate Infuse IV over 10 minutes, no pause Note: Picture shows pump set to max dose of 90mL over 10 minutes

11 Nursing Staff Step 4: If Dose Volume is >60mL (Patient weight 60Kg) via Drug Vial When study drug bottle is empty and fill chamber running low/to keep the line from running dry: *Un-spike drug vial, spike line with saline still using same primary infusion line *Clinical team can use the Y or piggyback method when administering chase This will need to be done to chase correct infusion dose through tubing Do not flush Alaris tubing after dose is infused Disconnect line from T-Connector and discard before administering anything else to patient. Keep vial for study team Note: T-Connector does not need to be disconnected. The 0.55mL of fluid in T-Connector is okay.

12 For routine questions, contact study team at For Immediate questions contact the ESETT study on-call at

13 STEP 1: E S E T T Procedure Demonstration of Max Dose if patient weighs 75Kg: 90mL over 10 minutes (rate of 540 ml/h) Open vent on primary IV pump tubing Spike study drug glass vial Prime line with drug STEP 2: Feed primed line into Alaris pump Connect infusion line to patient STEP 3: STEP 1 Study Drug (100mL) STEP 4 Saline Program pump to deliver volume/rate indicated on dose administration chart o Second nurse confirm volume and rate o 90mL at rate of 540 ml/h if patient weighs 75Kg o Correlates to an infusion over 10 minutes STEP 2 Alaris tubing STEP 4: STEP 5: Near end of 10 min infusion when study drug bottle is empty: o *Un-spike drug vial, spike line with saline using same primary infusion line This will need to be done to chase correct infusion dose through tubing at same rate 90mL can then go into patient STEP 3 Alaris Pump To patient Do NOT Flush Alaris tubing Disconnect line from T-Connector and discard Keep vial for study team Note: T-Connector does not need to be disconnected. The 0.55mL of fluid in T-Connector is okay. *Clinical team can use the Y or piggyback method when administering chase HUM Last updated:

14 ESETT HUM Study Title: Established Status Epilepticus Treatment Trial (ESETT) A multicenter, randomized, blinded, comparative effectiveness study of fosphenytoin, valproic acid, or levetiracetam in the emergency department treatment of patients with benzodiazepine-refractory status epilepticus. PI PEDS: A. Rogers, MD PI Adult: R. Silbergleit, MD RC Contact Information Study Purpose Social Work Guide to ESETT Office phone: Pager: On-Call: (Please leave name and number) Most seizures either stop on their own without treatment or stop with initial emergency treatments (medications such as Valium). Seizures that persist even with initial medications are more dangerous. The purpose of this study is to find out which of three commonly used medicines is most effective in patients who have seizures that continue despite initial emergency treatments. The three medicines are fosphenytoin (also called Cerebyx, similar to Dilantin), levetiracetam (also called Keppra) and valproic acid (also called Depacon or Depakote). Study Participation Risks Financial Information All three medications are regularly used by doctors currently to treat this type of severe seizures but doctors do not know which one works the best. This is the purpose of this study, doctors usually choose one of the three drugs based on their own experience this study also randomly chooses on of the three drugs to give. No other aspect of routine care was affected by enrollment in the study. Someone from the research team will be here shortly to explain more in detail. Continued study participation is completely voluntary. Participation lasts until hospital discharge no further medications or testing will be required. The medical risks and discomforts of receiving the study medications are similar to the risks of getting standard care. This is because by being in the study and receiving one of the three drugs does not deviate from the standard care you would have otherwise received. The study medicines are provided free of charge. You or your health plan will pay for all the things you would have paid for even if you were not in the study, like: Health care given during the study as part of your regular care Items or services needed to give you study drugs or devices Monitoring for side effects or other problems Deductibles or co-pays for these items or services. You will not receive payment for being in the study. Privacy To protect your privacy, the information about you gathered for this study will be coded with a special study number rather than your name (example: subject #2 ). Your name and information that could identify you will be stored separately in a secure study database. Information about you stored in your medical records and in the study database will only be reviewed by those overseeing this project.

15 - Inclusion - Seizing for >5 min Continued despite adequate benzo - Last dose of benzos given 5-30 min ago - Age 2 yrs Charge Nurses: - PEDS: ( ) (0974) - Adult: ( ) (9458) PIs: - Rogers: (C: ) (P:15364) - Silbergleit: (C: ) (P:10703) -Cator: (C: ) (P:11914) RCs: - Google Voice: ( ) - Inclusion - Seizing for >5 min Continued despite adequate benzo - Last dose of benzos given 5-30 min ago - Age 2 yrs Charge Nurses: - PEDS: ( ) (0974) - Adult: ( ) (9458) PIs: - Rogers: (C: ) (P:15364) - Silbergleit: (C: ) (P:10703) -Cator: (C: ) (P:11914) RCs: - Google Voice: ( ) - Inclusion - Seizing for >5 min Continued despite adequate benzo - Last dose of benzos given 5-30 min ago - Age 2 yrs Charge Nurses: - PEDS: ( ) (0974) - Adult: ( ) (9458) PIs: - Rogers: (C: ) (P:15364) - Silbergleit: (C: ) (P:10703) -Cator: (C: ) (P:11914) RCs: - Google Voice: ( ) PI Hotline: ESETT-PI ( ) - Inclusion - Seizing for >5 min Continued despite adequate benzo - Last dose of benzos given 5-30 min ago - Age 2 yrs Charge Nurses: - PEDS: ( ) (0974) - Adult: ( ) (9458) PIs: - Rogers: (C: ) (P:15364) - Silbergleit: (C: ) (P:10703) -Cator: (C: ) (P:11914) RCs: - Google Voice: ( ) PI Hotline: ESETT-PI ( ) - Inclusion - Seizing for >5 min Continued despite adequate benzo - Last dose of benzos given 5-30 min ago - Age 2 yrs Charge Nurses: - PEDS: ( ) (0974) - Adult: ( ) (9458) PIs: - Rogers: (C: ) (P:15364) - Silbergleit: (C: ) (P:10703) -Cator: (C: ) (P:11914) RCs: - Google Voice: ( ) PI Hotline: ESETT-PI ( ) - Inclusion - Seizing for >5 min Continued despite adequate benzo - Last dose of benzos given 5-30 min ago - Age 2 yrs Charge Nurses: - PEDS: ( ) (0974) - Adult: ( ) (9458) PIs: - Rogers: (C: ) (P:15364) - Silbergleit: (C: ) (P:10703) -Cator: (C: ) (P:11914) RCs: - Google Voice: ( ) PI Hotline: ESETT-PI ( ) - Inclusion - Seizing for >5 min Continued despite adequate benzo - Last dose of benzos given 5-30 min ago - Age 2 yrs Charge Nurses: - PEDS: ( ) (0974) - Adult: ( ) (9458) PIs: - Rogers: (C: ) (P:15364) - Silbergleit: (C: ) (P:10703) -Cator: (C: ) (P:11914) RCs: - Google Voice: ( ) PI Hotline: ESETT-PI ( ) - Inclusion - Seizing for >5 min Continued despite adequate benzo - Last dose of benzos given 5-30 min ago - Age 2 yrs Charge Nurses: - PEDS: ( ) (0974) - Adult: ( ) (9458) PIs: - Rogers: (C: ) (P:15364) - Silbergleit: (C: ) (P:10703) -Cator: (C: ) (P:11914) RCs: - Google Voice: ( ) PI Hotline: ESETT-PI ( ) - Inclusion - Seizing for >5 min Continued despite adequate benzo - Last dose of benzos given 5-30 min ago - Age 2 yrs Charge Nurses: - PEDS: ( ) (0974) - Adult: ( ) (9458) PIs: - Rogers: (C: ) (P:15364) - Silbergleit: (C: ) (P:10703) -Cator: (C: ) (P:11914) RCs: - Google Voice: ( ) PI Hotline: ESETT-PI ( ) - Inclusion - Seizing for >5 min Continued despite adequate benzo - Last dose of benzos given 5-30 min ago - Age 2 yrs Charge Nurses: - PEDS: ( ) (0974) - Adult: ( ) (9458) PIs: - Rogers: (C: ) (P:15364) - Silbergleit: (C: ) (P:10703) -Cator: (C: ) (P:11914) RCs: - Google Voice: ( ) PI Hotline: ESETT-PI ( ) RC/Attending Pocket Card (FRONT)

16 - Exclusion - Known pregnancy, severe metabolic/liver/renal disease - Known allergy or contraindication to: phenytoin (Dilantin), fosphenytoin (Cerebyx), levetiracetam (Keppra), or valproic acid (Depakote) - For this episode of status epilepticus: already given intravenous 2 nd line anticonvulsant or non-benzo sedatives with anticonvulsant properties (propofol, etomidate, ketamine, etc) or endotracheally intubated - Status epilepticus thought to be caused by: hypoglycemia <50mg/dL, hyperglycemia >400mg/dL, acute traumatic brain injury, cardiac arrest/post anoxia - Exclusion - Known pregnancy, severe metabolic/liver/renal disease - Known allergy or contraindication to: phenytoin (Dilantin), fosphenytoin (Cerebyx), levetiracetam (Keppra), or valproic acid (Depakote) - For this episode of status epilepticus: already given intravenous 2 nd line anticonvulsant or non-benzo sedatives with anticonvulsant properties (propofol, etomidate, ketamine, etc) or endotracheally intubated - Status epilepticus thought to be caused by: hypoglycemia <50mg/dL, hyperglycemia >400mg/dL, acute traumatic brain injury, cardiac arrest/post anoxia - Exclusion - Known pregnancy, severe metabolic/liver/renal disease - Known allergy or contraindication to: phenytoin (Dilantin), fosphenytoin (Cerebyx), levetiracetam (Keppra), or valproic acid (Depakote) - For this episode of status epilepticus: already given intravenous 2 nd line anticonvulsant or non-benzo sedatives with anticonvulsant properties (propofol, etomidate, ketamine, etc) or endotracheally intubated - Status epilepticus thought to be caused by: hypoglycemia <50mg/dL, hyperglycemia >400mg/dL, acute traumatic brain injury, cardiac arrest/post anoxia - Prisoner - Opt-out identification - Exclusion - Known pregnancy, severe metabolic/liver/renal disease - Known allergy or contraindication to: phenytoin (Dilantin), fosphenytoin (Cerebyx), levetiracetam (Keppra), or valproic acid (Depakote) - For this episode of status epilepticus: already given intravenous 2 nd line anticonvulsant or non-benzo sedatives with anticonvulsant properties (propofol, etomidate, ketamine, etc) or endotracheally intubated - Status epilepticus thought to be caused by: hypoglycemia <50mg/dL, hyperglycemia >400mg/dL, acute traumatic brain injury, cardiac arrest/post anoxia - Prisoner - Opt-out identification - Exclusion - Known pregnancy, severe metabolic/liver/renal disease - Known allergy or contraindication to: phenytoin (Dilantin), fosphenytoin (Cerebyx), levetiracetam (Keppra), or valproic acid (Depakote) - For this episode of status epilepticus: already given intravenous 2 nd line anticonvulsant or non-benzo sedatives with anticonvulsant properties (propofol, etomidate, ketamine, etc) or endotracheally intubated - Status epilepticus thought to be caused by: hypoglycemia <50mg/dL, hyperglycemia >400mg/dL, acute traumatic brain injury, cardiac arrest/post anoxia - Prisoner - Opt-out identification - Exclusion - Known pregnancy, severe metabolic/liver/renal disease - Known allergy or contraindication to: phenytoin (Dilantin), fosphenytoin (Cerebyx), levetiracetam (Keppra), or valproic acid (Depakote) - For this episode of status epilepticus: already given intravenous 2 nd line anticonvulsant or non-benzo sedatives with anticonvulsant properties (propofol, etomidate, ketamine, etc) or endotracheally intubated - Status epilepticus thought to be caused by: hypoglycemia <50mg/dL, hyperglycemia >400mg/dL, acute traumatic brain injury, cardiac arrest/post anoxia - Prisoner - Opt-out identification - Exclusion - Known pregnancy, severe metabolic/liver/renal disease - Known allergy or contraindication to: phenytoin (Dilantin), fosphenytoin (Cerebyx), levetiracetam (Keppra), or valproic acid (Depakote) - For this episode of status epilepticus: already given intravenous 2 nd line anticonvulsant or non-benzo sedatives with anticonvulsant properties (propofol, etomidate, ketamine, etc) or endotracheally intubated - Status epilepticus thought to be caused by: hypoglycemia <50mg/dL, hyperglycemia >400mg/dL, acute traumatic brain injury, cardiac arrest/post anoxia - Prisoner - Opt-out identification - Exclusion - Known pregnancy, severe metabolic/liver/renal disease - Known allergy or contraindication to: phenytoin (Dilantin), fosphenytoin (Cerebyx), levetiracetam (Keppra), or valproic acid (Depakote) - For this episode of status epilepticus: already given intravenous 2 nd line anticonvulsant or non-benzo sedatives with anticonvulsant properties (propofol, etomidate, ketamine, etc) or endotracheally intubated - Status epilepticus thought to be caused by: hypoglycemia <50mg/dL, hyperglycemia >400mg/dL, acute traumatic brain injury, cardiac arrest/post anoxia - Prisoner - Opt-out identification - Exclusion - Known pregnancy, severe metabolic/liver/renal disease - Known allergy or contraindication to: phenytoin (Dilantin), fosphenytoin (Cerebyx), levetiracetam (Keppra), or valproic acid (Depakote) - For this episode of status epilepticus: already given intravenous 2 nd line anticonvulsant or non-benzo sedatives with anticonvulsant properties (propofol, etomidate, ketamine, etc) or endotracheally intubated - Status epilepticus thought to be caused by: hypoglycemia <50mg/dL, hyperglycemia >400mg/dL, acute traumatic brain injury, cardiac arrest/post anoxia - Prisoner - Opt-out identification - Exclusion - Known pregnancy, severe metabolic/liver/renal disease - Known allergy or contraindication to: phenytoin (Dilantin), fosphenytoin (Cerebyx), levetiracetam (Keppra), or valproic acid (Depakote) - For this episode of status epilepticus: already given intravenous 2 nd line anticonvulsant or non-benzo sedatives with anticonvulsant properties (propofol, etomidate, ketamine, etc) or endotracheally intubated - Status epilepticus thought to be caused by: hypoglycemia <50mg/dL, hyperglycemia >400mg/dL, acute traumatic brain injury, cardiac arrest/post anoxia - Prisoner - Opt-out identification RC/Attending Pocket Card (BACK)

17 Established Status Epilepticus Treatment Trial (ESETT) Inclusion: Any ESE patient and is: 2 yrs Continued/recurring seizure for >5 min. Adequate dose of benzos given 5-30 min. ago Purpose: Which of these drugs: fosphenytoin, valproic acid, and levetiracetam is safer and more effective. ESETT Study Team On-Call: (outside #) Training Videos: nett.umich.edu/clinical-trials/esett/clinicians-only Established Status Epilepticus Treatment Trial (ESETT) Inclusion: Any ESE patient and is: 2 yrs Continued/recurring seizure for >5 min. Adequate dose of benzos given 5-30 min. ago Purpose: Which of these drugs: fosphenytoin, valproic acid, and levetiracetam is safer and more effective. ESETT Study Team On-Call: (outside #) Training Videos: nett.umich.edu/clinical-trials/esett/clinicians-only Established Status Epilepticus Treatment Trial (ESETT) Inclusion: Any ESE patient and is: 2 yrs Continued/recurring seizure for >5 min. Adequate dose of benzos given 5-30 min. ago Purpose: Which of these drugs: fosphenytoin, valproic acid, and levetiracetam is safer and more effective. ESETT Study Team On-Call: (outside #) Training Videos: nett.umich.edu/clinical-trials/esett/clinicians-only Established Status Epilepticus Treatment Trial (ESETT) Inclusion: Any ESE patient and is: 2 yrs Continued/recurring seizure for >5 min. Adequate dose of benzos given 5-30 min. ago Purpose: Which of these drugs: fosphenytoin, valproic acid, and levetiracetam is safer and more effective. ESETT Study Team On-Call: (outside #) Training Videos: nett.umich.edu/clinical-trials/esett/clinicians-only Established Status Epilepticus Treatment Trial (ESETT) Inclusion: Any ESE patient and is: 2 yrs Continued/recurring seizure for >5 min. Adequate dose of benzos given 5-30 min. ago Purpose: Which of these drugs: fosphenytoin, valproic acid, and levetiracetam is safer and more effective. ESETT Study Team On-Call: (outside #) Training Videos: nett.umich.edu/clinical-trials/esett/clinicians-only Established Status Epilepticus Treatment Trial (ESETT) Inclusion: Any ESE patient and is: 2 yrs Continued/recurring seizure for >5 min. Adequate dose of benzos given 5-30 min. ago Purpose: Which of these drugs: fosphenytoin, valproic acid, and levetiracetam is safer and more effective. ESETT Study Team On-Call: (outside #) Training Videos: nett.umich.edu/clinical-trials/esett/clinicians-only Established Status Epilepticus Treatment Trial (ESETT) Inclusion: Any ESE patient and is: 2 yrs Continued/recurring seizure for >5 min. Adequate dose of benzos given 5-30 min. ago Purpose: Which of these drugs: fosphenytoin, valproic acid, and levetiracetam is safer and more effective. ESETT Study Team On-Call: (outside #) Training Videos: nett.umich.edu/clinical-trials/esett/clinicians-only Established Status Epilepticus Treatment Trial (ESETT) Inclusion: Any ESE patient and is: 2 yrs Continued/recurring seizure for >5 min. Adequate dose of benzos given 5-30 min. ago Purpose: Which of these drugs: fosphenytoin, valproic acid, and levetiracetam is safer and more effective. ESETT Study Team On-Call: (outside #) Training Videos: nett.umich.edu/clinical-trials/esett/clinicians-only Established Status Epilepticus Treatment Trial (ESETT) Inclusion: Any ESE patient and is: 2 yrs Continued/recurring seizure for >5 min. Adequate dose of benzos given 5-30 min. ago Purpose: Which of these drugs: fosphenytoin, valproic acid, and levetiracetam is safer and more effective. ESETT Study Team On-Call: (outside #) Training Videos: nett.umich.edu/clinical-trials/esett/clinicians-only Established Status Epilepticus Treatment Trial (ESETT) Inclusion: Any ESE patient and is: 2 yrs Continued/recurring seizure for >5 min. Adequate dose of benzos given 5-30 min. ago Purpose: Which of these drugs: fosphenytoin, valproic acid, and levetiracetam is safer and more effective. ESETT Study Team On-Call: (outside #) Training Videos: nett.umich.edu/clinical-trials/esett/clinicians-only

18 Company Name Employee Name Position Title Street Address Address 2 City, ST ZIP Co de Phone: Fax: E - m a i l a d d r e s s Company Name Employee Name Position Title Company Name Employee Name Position Title Street Address A ddress 2 City, ST ZIP Co de Phone: Fax: E - m a i l a d d r e s s Street Address Address 2 City, ST ZIP Co de Phone: Fax: E - m a i l a d d r e s s Company Name Employee Name Position Title Company Name Employee Name Position Title Street Address A ddress 2 City, ST ZIP Co de Phone: Fax: E - m a i l a d d r e s s Street Address Address 2 City, ST ZIP Co de Phone: Fax: E - m a i l a d d r e s s Company Name Employee Name Position Title Company Name Employee Name Position Title Street Address Address 2 City, ST ZIP Co de Phone: Fax: E - m a i l a d d r e s s Street Address Address 2 City, ST ZIP Co de Phone: Fax: E - m a i l a d d r e s s Company Name Employee Name Position Title Company Name Employee Name Position Title Street Address Address 2 City, ST ZIP Co de Phone: Fax: E - m a i l a d d r e s s Street Address Address 2 City, ST ZIP Co de Phone: Fax: E - m a i l a d d r e s s

19 ESETT HUM Study Title: Established Status Epilepticus Treatment Trial (ESETT) A multicenter, randomized, blinded, comparative effectiveness study of fosphenytoin, valproic acid, or levetiracetam in the emergency department treatment of patients with benzodiazepine-refractory status epilepticus. PI Adult: R. Silbergleit, MD, PI PEDS: A. Rogers, MD RESEARCH COORDINATOR ENROLLMENT GUIDE E N R O L L M E N T P R O C E D U R E 1. Ensure ESETT box is in resus bay Press Start Protocol on PAD AT SAME TIME as drug infusion! (If this window is missed, do not Start Protocol ) Verbalize status and ask recording nurse to note in patient s chart: When seizure stopped and if seizure resumes 2. Complete Drug Administration Card (located front, inside cover) Put Patient ID sticker on ESETT Drug Admin Card Write down vial number. Once done, dispose vial in black plastic bin for glass. 3. Check: Ensure ED Patient Timeline depicts accurate drug infusion start time should be 10 minutes before medication stop time. If you know for a fact when drug infusion started, ask recording nurse to correct in timeline. 4. Be sure recording nurse notes pt s status in chart at the 20 and 60 min assessments time points! After 60 min assessment: if unblinding is needed press Unblind; on PAD if not, press Complete Protocol. (Unblinding will not be an option through the PAD after pressing Complete Protocol must then call hotline. Unblinding before 60 min is a protocol violation) 5. When calm, approach family for consent (may consult with social work if they have already met w/family). Give family copy of consent and signature page Ask the subject or surrogate to complete the ESETT survey after consent or withdraw (Highlight Q4b only needs one answer response) Complete the Demographics CRF (Form 505) Complete the Prior Relevant Home Medications CRF (Form 108) and ask family if pt had taken any current medications listed in EMR in the last 24 hrs. If a child (7-14 yo) is enrolled, continue to monitor for assent. If they are not able (cognitive impairment, medically unstable up to discharge, etc.) write a NTF as to why assent was not obtained. If they refuse, complete withdrawal form that is attached to consent form 6. Complete the Informed Consent Log CRF (Form 211) Be thorough! (If LAR is not at bedside at time of infusion: document where they are, and if a significant amount of time has passed between start of infusion and approach for consent document why, document every attempts/contacts.) 7. PAD and back-up vial: Select Submit Results option, exit out of app and charge device. Retrieve back-up vial from Adult ED pharmacy to reload the use-next box. Sign in when entering pharm fridges. Set up device: Open app Scan back-up vial code. Log in to WebDCU Drug Tracking Drug Receiving Click blue number next to back-up vial Scan code on computer screen. Touch Continue Setup. Contact info stays the same. Save. (This needs to be repeated once replacement vial comes in!) Ensure device is off and wifi is still connected. Disinfect PAD. 1

20 C O N S E N T I N T R O D U C T I O N NOTE: Subjects who are deemed competent and have no LAR present can consent and complete the Survey. Subjects who are not deemed competent and have no LAR present, follow-up with social work on what attempts have been made to contact LAR and status. Document your efforts on Form 211. Introduce yourself as a member of the research staff: I was asked to tell you about a research study we are doing of medications for seizures that don t stop with initial treatment. When the seizure did not stop, [Prefix last name] was entered into the ESETT Study. Introduce Study: The purpose of the study is to find out which of three commonly used medicines is safer and more effective at stopping a prolonged seizure that does not stop after receiving a full dose of medicine (like Valium). This condition is known as Established Status Epilepticus. The study is called ESETT or Established Status Epilepticus Treatment Trial. When patients have seizures that do not stop after treatment with benzodiazepines, doctors commonly use one of three meds: fosphenytoin (Cerebyx) levetiracetam (Keppra) valproic acid (Depacon) Despite being commonly used, we do not have any scientific evidence on which is most effective. Therefore, we (UMich) are involved in a study to systematically study the drugs. Because seizures require immediate treatment and any delay can be dangerous, we have permission to obtain informed consent after the seizure has been treated. Your loved one has been treated under the study protocol. The FDA has asked us to continue collecting information from the medical record to help determine which medicine is the safest and most effective. We do require your consent as the LAR to continue to collect this information. If you agree to continue to participate we will: Collect medical information until discharge from the hospital No aspect of your medical care will be affected by the study enrollment No further medications or tests will be required. We will collect: Demographics Info on your condition and treatment in the emergency department, Medical history, Information on recurrent seizures in the hospital, Some tests and laboratory results during your hospitalization, Adverse events, Dates of hospital admission and discharge. Your participation will end when you are discharged from the hospital. If you decide not to continue, no further information will be collected about you. Data collected prior to withdraw will remain in the study in order that we can monitor the safety of these medications. Do you have any questions for me at this time? 2

21 Consent Checklist Study explanation and enrollment Standard care vs. study procedure EFIC explanation Participation is voluntary Risks and benefits C O N S E N T T A L K I N G P O I N T S Talking points for each page of consent form: P1. Study Explanation and Enrollment: This study is being done at about 40 hospitals around the country. As noted, [Prefix last name] was enrolled in the study at the time of seizure treatment and the outcome of the treatment has been noted for the study. Standard care vs. study procedure: The drugs used in this study are all commonly and routinely used for treatment of seizures that do not respond to benzodiazepines (valium) P2. All people over the age of 2 who come to these hospitals with an ongoing seizure that has not responded to initial treatments are being given medication that is systematically chosen by the study. P3. Risks and Benefits: The risks and benefits are comparable to that of normal clinical treatment for a seizure like this. The different medications used by doctors that we are testing have different side effects, which you can read more about here. But they are all thought to be safe for clinical use and have a low incidence of serious side effects. The only risk to allowing us to continue collecting information from the medical record is the low risk of breach of confidentiality. Any time information is recorded somewhere, there s a chance it could end up somewhere it s not supposed to be; but we have many security measures in place, and only HIPAA-certified study team members will handle [Prefix last name] information for this study. P4. Participation is Voluntary: You can ask us to stop collecting medical data at any time. Some of his/her data may still be used just to help us know if the medicine he/she was given was safe and effective. If you agree to continue in the study, we will only collect his/her information until the end of the hospital visit. P5. The medicine we are studying was provided free of charge. There will be no costs to you related to being in the study. P6. All of the information we collect in this study is protected by HIPAA, the Health Insurance Portability Act, which is the same set of regulations that govern your medical record. This means that no one will see your information except for study team members who are trained in privacy laws. Now, if you would like to continue in the study and give us permission to collect [Prefix last name] medical information until he/she is out of the hospital, I will have you sign this page. If you do not want to continue in the study and you would like to withdraw now, I will have you sign this page. 3

22 NOTE: Paper DCFs are to be completed first. Hierarchy of initial source information: 1.) Discussion with treatment team (also live observation), 2.) Patient s electronic medical record, and 3.) PAD. 1. Check the survey after it is returned for 1) completion and 2) Q4b has only one answer selected. 2. If a child (7-14 yo) is enrolled, continue to monitor for assent until end-of-study. If they are not able (cognitive impairment, medically unstable up to discharge, etc.) be sure to write a NTF as to why assent was not obtained. If subject refuses (regardless if consent was signed from LAR previously), complete withdrawal form (attached to consent form), no further data will be collected. 3. Enter patient information in MBECT. (MBECT batch loads to MiChart every few hours, cannot associate patient with research study until this happens. You CAN, however, upload the research note.) P O S T E N R O L L M E N T 4. Go to WebDCU Add New Subject, complete information, save record, click green arrow for Subject CRF Binder. Most other DCFs can wait (based on CRF Completion Timeline on back) if necessary. 5. Complete F102 Randomization. Once submitted, this will trigger a drug resupply. 6. Complete F108 Prior Home Medications in case there is anything you need to ask the patient. 7. Enter Research Note and upload Informed Consent Document (ICD) to MiChart ASAP. Follow instructions! Located in S:// drive MiChart Training. Save scanned ICDs to S:// drive under POST Enrollment. If Sherry or PI enrolls a patient: Contact RC coming into office next 8. Upload Patient/Surrogate survey to the PECARN-Michigan folder in MBox. Alternatively, you can the completed survey to: upload.pecarn_.lpcciollku@u.box.com. Save uploaded survey in S://drive under POST Enrollment. 9. Enter enrollment in ESETT Internal Log excel spreadsheet and any notes located in S:// drive under POST Enrollment. 10. Recognize any outstanding RNs and pharmacists to receive Making a Difference award at: Add to GCal 24 hour mark: Check for any S/AEs and schedule 24 hour audit Check if replacement vial has come in. Continually check for this!! When it does, program device with new vial immediately and place back-up back in Adult pharm fridge. Ensure receipt of drug has been documented in WebDCU by IDS pharmacy. Log this information in ESETT Internal Log spreadsheet. 12. Audit patient at 24 hours and End of Study. All S/AEs are to be documented in paper DCFs, WebDCU, and ESETT Internal Log. Refer to AE Reporting Guidelines by the IRB located in S/AE tab under POST Enrollment. 13. End of Study: Complete Clinical Summary Packet. Folder with instructions located in S:// drive POST Enrollment. Upload to WebDCU and save to S:// drive. PI after all DCFs completed and folder audited to sign Form 126: End of Study in WebDCU. Be sure this information is documented in the paper DCF. Upload incomplete clinical summary packet if waiting on a physician to sign off on a note. Have PI sign form in order to submit it before the 5 day deadline. Write in notes the form is incomplete. 4

23 5

24 UNBLINDING Unblinding is an option on the PAD after 60 minute questions have been answered. If after 60 minutes and the device is no longer available, call PI Hotline (855-ESETT-PI) Emergency unblinding (unblinding prior to 60 minutes): Call PI Hotline(855-ESETT-PI) o Unblinding should be performed by clinical team rather than study team if possible. Study team should remain blinded. o Unblinding prior to the 60 minute primary outcome is a protocol violation. If interpreter is coming, wait to approach family until arrival. Refer to S:// drive Consent Non-English speaking short forms. If no interpreter is coming, approach clerk (maroon scrubs), ask to connect with language line or consent line on portable phone. Consent is recorded. Make NTF. o Save NTF in folder under POST Enrollment. NON-ENGLISH WORKFLOW: o Use short forms saved in the S:// drive (location above). If specific language is not offered in the S:// drive, search online resources for the specific short form needed. o Conduct the subject's informed consent process with the researcher and a translator fluent in English and the foreign-language present (a family member or others may also attend as long as no concerns regarding undue coercion from them on the subject is known). o The subject signs a 'short form' informed consent document written in the appropriate language if agreeing to participate o The researcher signs the currently approved informed consent document [ICD] in English o The witness (fluent in both languages) signs BOTH the short form and the English ICD. (Note, the translator may also serve as the witness or the investigator, but not as the investigator and the witness and the translator). o The subject is given a copy of BOTH the signed short form and signed English ICD o Provide the English ICD even though the subject may not understand English. o Copies of BOTH signed documents are maintained in the study records. Copies of both signed documents are uploaded in the subject's medical record. 6

25 A subject is considered enrolled and randomized at the same time point, defined as the time that study drug infusion is initiated. LAR: Legally Authorized Representative. An LAR is typically defined as: a.) Health-care agent; b.) Adult child (18 yrs or older); c.) Parent; d.) Adult sibling; e.) Grandparent; f.) Adult grandchild (18 yrs or older). When more than one LAR is present, the closest relative, as defined above, should give consent. MoP: Manual of Procedures found here: t?pli=1 WebDCU: Enter new subject here: Definitions and Locations MBECT: Enter new subject here: Non-English-speaking consent forms and SOP: S:// drive ESETT Consent Non-Englishspeaking short forms S/AE reporting: See CTCAE and Safety Monitoring Plan under S:// drive ESETT MoP Supporting documents. Research Notes and upload Informed Consent Documents to MiChart instructions: S:// drive MiChart Training PAD Instructions: S:// drive ESETT MoP Supporting documents PAD User Manual Change vial codes in PAD: S:// drive ESETT Training Materials PAD Training 7

26 Google Voice: C O N T A C T S Charge Nurse Desks: CES (phone: ) (page: 0974) AES (phone: ) (page: 9458) Paging Number: PIs: Alex Rogers (cell: ) (page: 15364) alexroge@med.umich.edu Allison Cator (cell: ) (page: 11914) acator@med.umich.edu Robert Silbergleit (cell: ) (page: 10703) robie@med.umich.edu RCs: Office Pager Sherry Goldfarb (cell: ) (office: ) Goldfarb@med.umich.edu Noelle Herzog (cell: ) noellel@med.umich.edu Stephanie Johnson (cell: ) nuseigus@med.umich.edu Cate Flechsig (cell: ) cflechsi@med.umich.edu PI Hotline: 855-ESETT-PI ( ) Pharmacy: CES (mobile phone: ) (page: 35942) AES (mobile phone: ) (page: 32818) If an emergency comes up and there is NO coverage: SUSPEND STUDY 1.) First try contacting other RCs and/or PIs to cover 2.) If no coverage: a. Call CES and AES mobile phones (CES: ; AES: ) i. Give instruction to place the ESETT Study Suspended sign on the box. 1. Sign is located in the research binder. ii. Let them know time/day of study stop and time/day of suspected study start this information will need to be written on the sign. 1. Be sure to follow-up when study starts that the sign is taken off. iii. Pam Walker plada@med.umich.edu this information. 1. She will then send a notification to all of pharmacy staff. iv. Text ESETT Group and to let the team know the study has been suspended and for how long. 1. any PI not on ESETT Group text this information. 8