1. PI and Coordinator Webinar
August 28, 2018

2. Site startup 112 → 116 completed trial agreements
94 → 108 CIRB submissions
91 → 102 CIRB approvals
79 → 89 readiness calls
78 → 87 sites released to enroll
28 → 33 sites with at least one randomization

3. Enrollment 264 patients consented 42% eligible for randomization
73 randomized
20 more eligible but NOT yet randomized

4. Days Since Last Randomized#
Site Name
Consented
Total Randomized
Monthly Randomized
Days Since Last Randomized
Total
264 73
0.24 3 1
United Hospital, St. Paul, MN 18 6
1.53 25 2
Oregon Health & Science University Hospital, Portland, OR 17
1.56
University of Iowa Hospitals & Clinics, Iowa City, IA 15
1.23 28 4
Medical University of South Carolina University Hospital, Charleston, SC 13
0.58 5
University of Cincinnati Medical Center, Cincinnati, OH 12
0.72
Intercoastal Medical Group - Hyde Park, Sarasota, FL
0.52 7
UF Health Shands Hospital, Gainesville, FL 8
0.57 48
UPMC Presbyterian Hospital, Pittsburgh, PA
0.31 41 9
Hospital of the University of Pennsylvania, Philadelphia, PA
0.6 38 10
Los Angeles County + USC Medical Center, Los Angeles, CA
0.56 11
Northwestern Memorial Hospital, Chicago, IL
0.18
Memorial Hermann Texas Medical Center, Houston, TX
0.35
143
Harborview Medical Center, Seattle, WA 14
OSU Wexner Medical Center, Columbus, OH
0.29
NYP Weill Cornell Medical Center, New York, NY
0.39 84 16
Intermountain Medical Center, Murray, UT
0.2 49
Massachusetts General Hospital, Boston, MA 39
University of Kentucky Hospital, Lexington, KY 19
Vanderbilt University Hospital, Nashville, TN
0.49 20
University of Illinois Hospital, Chicago, IL
1.5

5. Randomizations

6. Superlatives Most Randomizations Last Week: (2 Randomized)
University of Cincinnati Medical Center, Cincinnati, OH
Top Randomizer: (6 randomizations)
University of Iowa Hospitals & Clinics, Iowa City, IA
United Hospital, St. Paul, MN
Oregon Health & Science University Hospital, Portland, OR
First Randomization for the Site:
Northwestern Memorial Hospital, Chicago, IL

7. Coordinator heroes
Vicki Streets (and Dr. Holmstedt) at MUSC for consenting 3 ARCADIA patients in one day (end of July)
Julie Bishop, coordinator at Mercy Health St. Mary’s
Was having challenges in that ECG had been done on admission, and stroke occurred 2 days later
Tried to see if could get ECG off Holter, no-go
Then saw a follow up visit with a cardiologist, arranged for ECG then

8. “Failure to enroll” warning notices
Some sites may begin to see warning notices ( s)
The original Clinical Trial Agreement specifies that sites can be put on probation for:
Failure to randomize a patient for three months
Failure to complete required documents/approvals/processes
Continued failure to enroll can lead to:
Retraining requirement
Termination of participation
We will focus initially on sites that have not CONSENTED any patients (rather than randomized)
We want all sites to succeed!

9. Further Recruitment Efforts
Recruitment Innovation Center (NIH Center, part of National Center for Advancing Translational Science [NCATS])
Will be calling top and bottom performing sites to get more information about successful and unsuccessful strategies
Consider surveying patients who consent but then decide not to be randomized after eligible (this should not happen!)
May also consider surveying those who elect not to enroll at all
Plan to have Site PIs educate local/referring physicians/hospitals
Grand Rounds, Lunch and Learn, etc.
Will make slides available
Patient-facing
Patient brochure
Video: will appear on-line for patients who may search after a stroke for information
Website
Other ideas?

10. Irene’s slides…

11. ARCADIA Pharmacy Reminders
When study kits are shipped to your site they need to be “accepted” in webDCU™ before they are able to be dispensed.
Please talk to your pharmacists about the importance of accepting study drug in WebDCU in a timely manner.
You can add additional pharmacists to your study team/DOA so more people will have access to do this.
The pharmacy training video should be viewed by anyone accepting study drug. It is located on the webdcu campus training site:

12. ARCADIA Core Lab Reminders
Core lab tubes must be labeled with the Subject ID and the date
Don’t forget to include a copy of Form 503 v1: Biosample Collection/Shipping
If you are not able to ship specimens the same day, you will need to spin them down and refrigerate them. (Instructions are in section 12 of the Lab MOP)
Fill the tubes as much as possible.
For Core Lab Questions call the CALM Lab at: (212) or

13. ARCADIA Regulatory reminders & updates
All StrokeNet sites should be using ICF v5 now.
Any subject who consented on ICF v4 and who is still active in the study, should be re-consented at their next follow-up visit.
They will need to sign the Biobanking section again and the new consent should be uploaded to webDCU™ for monitoring.
If you edit your Delegation Log (DOA) in webDCU™ we do need to submit the changes to the CIRB as an administrative amendment.
Please bundle changes in personnel when possible. New study team members should not conduct study activities until the CIRB approves the DOA change.

14. DCU slides…

15. Lab Kit Requests
Lab kit re-supply will now be completed automatically based on a site’s inventory – no need to request via fax request form.
Please check your site’s inventory in WebDCU:
Please contact Erin Klintworth about any discrepancies

16. F288: Concomitant Medication Log

18. F288: Concomitant Medication Log
Concomitant medications will now be collected only for randomized subjects.
We will soon be asking you to review and confirm your F288 CRFs for randomized subjects are accurate.
The new concomitant medications CRF will only be posted at the baseline visit.
When a new visit is added, F288 will automatically be un-submitted. You will need to assess each medication and dosage at each visit, and mark if the medication and dosage is continuing or stopped and enter the corresponding date.
If a medication is continuing, but the dosage has changed, please mark the original medication and dosage as stopped, and enter the medication and new dosage on a new row with the start date for that dosage.
If a medication is taken twice a day, add the dosage together to receive a total “daily dose” which will be entered in column B.

19. Data-Related Reminders
Modified Rankin Scale score on F101: Inclusion and Exclusion Criteria is the mRS at the time of consent, not a pre-stroke mRS.
Please complete all CRFs for a visit within 5 days of the visit date. This includes all baseline CRFs for subjects that are consented but not eligible for randomization.
Please remember to add the End of Study visit and complete the relevant CRFs when a subject is found to be not eligible for randomization.
If a subject says they want to stop study medication, please confirm whether they are happy to continue to be followed otherwise, or if they want to withdraw consent completely.

20. Who to Contact?
Erin Klintworth at NDMC When to contact: If you have WebDCU-related DOA or regulatory database questions Faria Khattak at NDMC When to contact: Any other WebDCU-related or CRF-related questions
Holly Pierce at NDMC
When to contact: Any other WebDCU-related or CRF-related questions
Jocelyn Anderson at NDMC
When to contact: Any other WebDCU-related or CRF-related questions

21. FAQs

22. FAQ
Q: Is a patient with a central retinal artery occlusion eligible? A: Yes, if there is no other specific identifiable cause of the occlusion (e.g., carotid stenosis, giant cell arteritis, etc). Why? According to the 2013 AHA/ASA statement on the definition of an stroke, an ischemic stroke is “An episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction.” (italics added) Stroke. 2013;44(7): Plus, this definition is the same one used in our outcome definition of stroke, so it makes sense to include it as a criterion for enrollment as well.

23. FAQ
Q: We are hoping for some clarification on the type of hemorrhages that would exclude a patient. There is 1 chronic microhemorrhage in the right cerebellum, and some likely chronic petechial hemorrhagic conversion of R cerebellar infarcts. Is there a threshold for excluding patients with chronic ICH or multiple microhemorrhages suggestive of cerebral amyloid angiopathy? A: There is no formal exclusion based on asymptomatic microbleeds or asymptomatic chronic hemorrhages. This would be up to PI judgment. If there is a strong suspicion of amyloid angiopathy then that might be a patient to exclude. One way to think about this might be that if this is someone you would NOT anticoagulate if you found AF (and would instead place a WATCHMAN, for instance) then you probably shouldn't enroll them in the trial. If you would feel comfortable anticoagulating for AF, then you could probably consider them for ARCADIA.

24. FAQ
Q: I have a patient who had a colon resection for cancer in April of this year. Since he is called cryptogenic, it seems our doctor doesn’t see any concern for hypercoagulability due to the ca. Surprisingly to me, there isn’t any exclusion for ca in the protocol regardless of date. A1: There’s no doubt that cancer-related hypercoagulable contributes to stroke risk but these strokes still often meet criteria for cryptogenic or ESUS, so active cancer isn’t on its own an exclusion. A2: The other crucial factor is whether the treating primary MDs and oncologists are willing to have the patient randomized to apixaban vs aspirin. We don’t want the patient to be randomized only to have the oncologist insist on anticoagulation.

25. Hotline Calls – tracking in RedCap database
Caller Typecaller_type
Caller's Question:caller_q
Answer Given:q_answer
Site Coordinator (1)
Patient was interested but wanted to know how quickly unblinding could occur in case of emergency.
Within minutes.
After consenting patient, they realized that the echo was from 2 months prior. OK to proceed? They are planning to repeat the echo anyway.
As long as investigator feels it is ESUS based on the definition, OK to consent. If new echo obtained within 120 days of stroke, could be used as basis of randomization.
They consented a patient but were having trouble getting access to draw blood. They asked what to do in this case.
I told them to upload the ECG and review the echo for now, and to try to draw blood whenever they could as long as it's within the 120 day window.
Wanted to clarify if they should just fill the NT-proBNP tube if patient declined consent for biobank.
Yes.
Patient's cardiologist put her on aspirin 325 for stroke prevention. OK to enroll?
I advised them to speak with the cardiologist, explain lack of evidence supporting 325 over 81, and making sure there is buy in before consenting.
Patient is on two SSRIs--okay to consent?
SSRIs are discouraged but not prohibited. Up to site investigator and treating physicians how to handle.
Other (4)
Patient being seen for evaluation by a cardiologist who wanted to know whether on aspirin or apixaban. Not an emergency situation.
I explained that unblinding was reserved for emergency situations.
Site PI (2)
Patient had only carotid ultrasound, no intracranial imaging--eligible?
Unfortunately not. They are planning to get a CTA for clinical purposes anyway, so hopefully will enroll later.
Randomized subject was assigned to 2.5 mg apixaban kit and they wanted to confirm this was okay.
Seems correct since she met 2 criteria: age > 80 and weight < 60.
He was asking about which dose patient would get at time of randomization
I referred him to MOP which spells out criteria for possible low dose apixaban
Stroke fellow from UCSD wondering whether they could consent a patient with baseline creatinine of ~2 who came in with Cr of 2.8 and then it downtrended to 1.9.
Yes, eligible.
there was hemorrhagic conversion, asking if that was exclusion
NO, but does require delay until randomization if eligible for such. At least 14 days or more; should be clinically comfortable starting anticoagulation.
can patient with recent spontaneous SAH and aneurysms, most of which have been treated, be enrolled.
I answered NO. excluded by hx of spontaneous intracranial hemorrhage

28. Hotline 24-hour telephone hotline
Please use it for any urgent questions
Eligibility, randomization, unblinding, etc
( AR-CADI): useful to save in your cell phone
The hotline automatically calls the four PIs in succession
Please let it ring
And call back if no luck—one of us will pick up!
Please with non-urgent questions

29. Recruitment materials and study tools
Video
Patient brochure
Newsletters
Toolbox for minority recruitment

30. Open mike… Who is having challenges? Tell us what/how/where/why
High enrolling sites may have suggestions…

31. Thank you so much for your efforts to make ARCADIA a success!!
Next steps
Actively screen
Bring back randomization-eligible patients
Look for recruitment video
Send us feedback—we will make changes as needed to make this trial successful!
Thank you so much for your efforts to
make ARCADIA a success!!