Transcript Slide 1

Protocol
Nichol McBee, MPH, CCRP
BIOS Coordinating Center
Johns Hopkins University
Protocol Overview
Schedule of Events
Registration/Screening
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Diagnostic CT
Blood pressure control
Pregnancy test
Toxicology screen
Lab assessments
Concomitant treatments
NIHSS
Barthel Index (historic)
Modified Rankin scale (historic)
Early Notification is Important
Diagnostic CT
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Within 24 hours of symptom onset
Time 0
CT or CTA
ICH > 30 cc
Infratentorial hemorrhage
– Brainstem involvement or third nerve palsy
• No underlying pathology
Blood Pressure Control
• SBP < 180 mmHg
• 6 hours
• Long-term goal: MAP < 100 or 140/80
Pregnancy Test
• Urine or serum
• Prior to consent: Review if done standard of
care
• Post consent: Order if not done per standard
of care
• Pregnancy during follow-up
Toxicology Screen
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Cocaine, barbiturates, etc
Contributor(s) to the bleed
As close to presentation to ED as possible
Standard of care?
Data collection only
Lab Assessments
• Screening:
– Plt count
– INR
– Pregnancy test (if applicable)
• Once prior to randomization:
– Plasma plasminogen activity
– Fibrinogen
• Daily through day 6:
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WBC
Hct
Plt count
aPTT
INR
Concomitant Treatments
• Concomitant medications
• Concomitant procedures
NIHSS
• ED presentation
• Certified examiner
• Day 7, 30, 180, and 365
Barthel Index
• Screening: historical
• Level of functioning prior to symptom onset
• Comparison of scores at days 30, 90, 180, 270,
and 365
Modified Rankin Scale
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Screening: historical
0-1
Level of functioning prior to symptom onset
Comparison of scores at days 30, 90, 180, 270,
and 365
Post Consent Screening
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• Medical history/review
Informed consent
of systems
Stability CT
Blood pressure control • MRI/MRA (or CTA)
Pregnancy test
Toxicology screen
Lab assessments
Concomitant treatments
NIHSS
Modified Rankin Scale
Inclusion Criteria
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ICH ≥ 30 mL on dCT
GCS ≤ 14 or a NIHSS ≥ 6
ICH stability
Symptom onset < 24 h prior to dCT
MIS 12-72h post dCT
1st dose up to 76h post dCT
SBP < 180 mmHg
Historical mRS 0 or 1
Age ≥ 18 and ≤ 80
Exclusion Criteria
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Infratentorial hemorrhage
Intraventricular hemorrhage requiring EVD
Thalamic bleeds with midbrain extension
Irreversible impaired brain stem function
Underlying pathology
Unstable mass or evolving intracranial
compartment syndrome
Exclusion Criteria (cont.)
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Coagulopathy
Long-term anti-coagulation required
Dabigatran use
Systemic bleeding
Pregnancy
Allergy/sensitivity to rt-PA
Prior enrollment
Other interventional trial
Survival to d365 is not expected
Exclusion Criteria (cont.)
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Concurrent illness
Mechanical heart valve
Known risk for embolization
Investigator judgment
Active drug or alcohol use or dependence
that would interfere with follow-up
• Unstable patient who needs specific
intervention
• No consent
Randomization
• Only after I/E criteria satisfied and informed
consent signed
• Adaptive design
• Timelines
Post-Randomization/Pre-Surgery
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Lab assessments
Concomitant treatments
NIHSS
Barthel Index
Modified Rankin Scale
MRI/MRA
Day 1
(Day of Randomization)
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Medical management
Image-guided catheter placement + aspiration
Post catheter placement CT
Review of systems (post surgery)
rt-PA administration
Daily CT
Vital signs
Neurocheck
Lab assessments
Concomitant treatments
Medical Management
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ICP management
Neurological status
Cardiovascular management
Respiratory care
Nutritional support
DVT and PE prophylaxis
Withdrawal of care
MIS Procedure
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Credentialed neurosurgeon
Trajectory determination
Surgical Center review
Antibiotic therapy
Catheter placement
Post catheter placement CT
Stabilization period
Catheter adjustment/replacement
Review of Systems
Post Surgery
• Neurological status
• 3 hours post MIS
• Clinical worsening or improvement
DOSING
• Who
– Certified investigator or designee
• What
– 1.0mg/1.0mL of Cathflo followed by 3.0 mL of flush
• Where
– At the bedside
– Into the clot system
DOSING
• When
– 1st dose no sooner than 12 hours and no
later than 76 hours post Diagnostic CT scan
and after stability is confirmed.
– Every 8 hours for up to 9 doses
• How
– Sterile field
– Monitor vital signs
DOSING ELIGIBILITY
• Daily CT scans
• Catheter tract stability
• Dosing endpoints
Days 2 and 3
(Post Randomization)
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rt-PA administration
Daily CT
Vital signs
Neurocheck
Lab assessments
Concomitant treatments
DAILY SAFETY LABS
• Serum
– White blood cell
count
– Hematocrit
– Platelet count
– INR
– PT
– aPTT
– Plasminogen
– Fibrinogen
– D-dimer
Days 4-6
(Post Randomization)
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Daily CT (day 4)
CT 24h post catheter removal
Vital signs
Neurocheck
Lab assessments
Concomitant treatments
Day 7
(Post Randomization)
• MRI
• NIHSS
Follow-up
(Post Symptom Onset)
Day 30
±7
days
Daily CT Scan
Day 90 Day 180 Day 270 Day 365
±7
± 14
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Concomitant treatments
SOC
NIHSS
Barthel Index
Modified Rankin Scale
Stroke Impact Scale
GOS-E Scale
Mini-Mental Exam
Euro-Quol-5D Scale
PBSI
Personal Health Utility
Assessment Interview
SOC
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RESOURCE UTILIZATION
• ICU stay
• Hospital stay
• Time at home
CONCOMITANT MEDICATIONS
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7 days prior to symptom onset
Acute treatment phase
Follow-up phase
Required interventions
Prohibited interventions
Precautionary interventions
AE & SAE REPORTING
• All AEs and SAEs through day 7
• All SAEs and neurological AEs through day
365
• SAEs must be reported using the EDC
system
– No paper worksheet!
FINAL VISIT
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Day 365 follow-up visit
CT scan
Outcome Scales
Record new AE/SAE or procedures
– Neurosurgical procedures
• Confirm ongoing or document resolution of
previously recorded events