Transcript Document

MISTIE III - Inservice
Protocol v3.1
Inclusion/Exclusion Criteria
Randomization
Event Table and Timeline
Agenda
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Inclusion and exclusion criteria
Temporary inclusion criteria
Protocol timeline
Protocol activities by protocol period
Waiting periods for safety
Concomitant therapies
Medical Protocol At-A-Glance
Surgical Protocol At-A-Glance
BP control
MRI/MRA or CTA to
rule out underlying
pathology
ICH
MISTIE III
6+ hrs
CT to Demonstrate ICH Stability
& acquire images for Surgical
Planning and Image Guidance
Consent &
Randomization
Surgical Management:
Initiate surgery and give
1.0 mg rt-PA Q8hr for up
to 9 doses
Randomization
Dosing
MIS
Surgery
Diagnostic
Stability
Catheter
Removal
PostSurgery
Day: 1
24hr postremoval
2
3
4
5
6
7
30
90
180 270
Follow-up
= CT scan
= MRI
= Dose
*green indicates surgical patients only
365
Screening
BP control
MRI/MRA or CTA to
rule out underlying
pathology
ICH
MISTIE III
6+ hrs
CT to Demonstrate ICH Stability
& acquire images for Surgical
Planning and Image Guidance
Consent &
Randomization
Surgical Management:
Initiate surgery and give
1.0 mg rt-PA Q8hr for up
to 9 doses
Randomization
Dosing
MIS
Surgery
Diagnostic
Stability
Catheter
Removal
PostSurgery
Day: 1
24hr postremoval
2
3
4
5
6
7
30
90
180 270
Follow-up
= CT scan
= MRI
= Dose
*green indicates surgical patients only
365
Call the PI or Coordinator
INCLUSION CRITERIA
Inclusion
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Age 18-80
Spontaneous ICH ≥ 30 cc
GCS ≤ 14 or a NIHSS ≥ 6
Historical Rankin of 0-1
SBP < 180 mmHg for 6o
Dx CT scan within 24o symptom onset
Randomized within 72o of Dx CT
THE MISTIE TEAM WILL SCREEN ALL ICH
ADMISSIONS
….and decide further eligibility
EXCLUSION CRITERIA
Exclusion: Clot location
• Infratentorial hemorrhage
• IVH-related mass effect requiring EVD
• Thalamic bleeds with apparent midbrain
extension with third nerve palsy or dilated and
non-reactive pupils
• Irreversible impaired brain stem function:
Exclusion: Underlying Pathology
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Untreated ruptured cerebral aneurysm
Ruptured intracranial AVM
Treated aneurysm or AVM within 90 days
Tumor
Vascular malformations
Unstable mass or evolving intracranial
compartment syndrome
Exclusion: Screening Labs
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Bleeding w/in last 12o
Platelet count < 100,000
INR > 1.4
Elevated PT or aPTT
Known allergy/sensitivity to rt-PA
Dabigatran at symptom onset
Requiring long-term anticoagulation
Permitted: Reversing OAT*
• Pre-randomization & Post
– FFP (fresh frozen plasma)
– PCC (prothrombin complex concentrate)
– Vitamin K
– NovoSeven (Factor VII)
*oral anticoagulation therapy
Exclusion: Concurrent Illness
• Mechanical heart valve
• Known risk for embolization
BASELINE
EVENT TABLE & TIMELINE
Screening Period
Screening
Diagnostic CT
Diagnostic MRI/MRA
(or CTA/routine Angio)
Stability CT
X
Medical/Treatment History
X
Pregnancy Testing
X
Toxicology Screen
X
Barthel Index - Historical
X
Modified Rankin - Historical
X
Lab Assessments
X
Pre-Randomization
(Baseline)
X
X
X
Informed Consent
X
Blood pressure (over 6 hours)
X
NIHSS (to capture deterioration)
AE/SAE capture
Randomization
X
(capture if done)
X
Start recording
AE/SAEs
ACUTE TREATMENT PERIOD
Acute Treatment
BP control
MRI/MRA or CTA to
rule out underlying
pathology
ICH
MISTIE III
6+ hrs
CT to Demonstrate ICH Stability
& acquire images for Surgical
Planning and Image Guidance
Consent &
Randomization
Surgical Management:
Initiate surgery and give
1.0 mg rt-PA Q8hr for up
to 9 doses
Randomization
Dosing
MIS
Surgery
Diagnostic
Stability
Catheter
Removal
PostSurgery
Day: 1
24hr postremoval
2
3
4
5
6
7
30
90
180 270
Follow-up
= CT scan
= MRI
= Dose
*green indicates surgical patients only
365
Acute Treatment
ACUTE TX PERIOD
Days 1-6
Catheter Removal
Surgical Center Catheter
Review
X
X
Dosing: Q8Hr (+ / - 2 hrs)
Up to 9 doses
Open to drain for
24-36 hr post last dose
CT Scans
Days 1-4
24 hr post catheter
removal
Vital Signs: Q6Hr
X
Lab Assessments
X
AE/SAE capture
X
Neurological AEs, all
SAEs, and all Medical
Events of Interest
DOSING
Dosing Training
• Video link:
https://www.youtube.com/watch?v=wykMTk
duEeU
WAITING PERIODS FOR SAFETY
Hold Drug 24 Hours
• Clot expansions
• New catheter placements
• Catheter repositioning
After Dosing
• Leave catheter open
• Wait 24 – 36 hours between last dose and
catheter removal
• Obtain CT scan 24 hours after catheter
removal
FOLLOW UP PERIOD
Follow-up
BP control
MRI/MRA or CTA to
rule out underlying
pathology
ICH
MISTIE III
6+ hrs
CT to Demonstrate ICH Stability
& acquire images for Surgical
Planning and Image Guidance
Consent &
Randomization
Surgical Management:
Initiate surgery and give
1.0 mg rt-PA Q8hr for up
to 9 doses
Randomization
Dosing
MIS
Surgery
Diagnostic
Stability
Catheter
Removal
PostSurgery
Day: 1
24hr postremoval
2
3
4
5
6
7
30
90
180 270
Follow-up
= CT scan
= MRI
= Dose
*green indicates surgical patients only
365
Follow-up
Day 7
NIHSS and MRI
X
CT Scans
Days 30 & 180
Modified Rankin (video)
Days 30, 180, 365
Modified Rankin (no video)
Days 90 & 270
Functional outcomes
AE/SAE capture
Day30-365
X
X
Neurological AEs, all
SAEs, and all Medical
Events of Interest
Your Site # Here
24/7 Study Mobile Phone:
410-736-1368
Image Reading Center:
410-502-2949