Presented at the Third Annual Barsan Emergency Medicine Research Forum

1. Post-tPA ICH
INSTINCT Community Hospitals Vs Pooled Analysis
Rosemarie B Diaz, Benjamin D Hume, Darin B Zahuranec,
Lewis B Morgenstern, Cemal B Sozener, William J Meurer, Phillip A Scott

2. Intracerebral Hemorrhage
The threat of intracerebral hemorrhage is a significant
risk factor limiting the use of tPA in acute stroke.
Department of Emergency Medicine
(Von Kummer et al, 2002)

3. Settings with Low Rates of
Postthrombolytic Intracerebral Hemorrhage
Department of Emergency Medicine
Hospitals participating
in Clinical research
trials
Community Hospitals
with Primary Stroke
Centers Certification
Community Hospitals who
Participate in Get with the
Guideline Stroke Program
(Lees et al, 2010)

4. Department of Emergency Medicine
The INSTINCT Trial
Safety of IV tPA use in typical Community ED’s
and Hospitals had yet to be investigated until…
(Scott et al, 2013)

5. Rates of Post-tPA ICH
INSTINCT TRIAL vs. Pooled Analysis Data
Department of Emergency Medicine
INSTINCT EPITHET
ATLANTIS
ECASS
NINDS
(Scott et al, 2013)

6. Methods
Selection of Community Hospitals
Department of Emergency Medicine
(Scott et al, 2013)

7. Methods
Identification of ICH in tPA treated patients
Department of Emergency Medicine
Independent physician
panel reviewed complete
medical records of all tPA
treated strokes from
2007-2010
Any evidence
of possible ICH
Primary Review Secondary Review
Two vascular neurologists
blinded to original
interpretation of all
clinical data classified
each possible ICH using
ECASS criteria
(Scott et al, 2013)

8. Department of Emergency Medicine
ECASS Criteria
(Hacke et al, 1998)

9. Department of Emergency Medicine
ECASS Criteria
(Hacke et al, 1998)

10. Data Collection
Department of Emergency Medicine
• We located, de-identified, abstracted, and analyzed medical
records for all 557 patients treated with alteplase after
randomization according to protocol (100% capture).
• Overall 99,066 of 100,260 (99%) individual data fields sought were
obtained.
• Inter-rater agreement for coordinator abstracted elements was
94% (2049 of 2170) overall and 96% (374 of 390) for a-priori
identified critical elements.
• Inter-rater agreement between physician reviewers was 98%
(17,383 of 17,824).
(Scott et al, 2013)

11. INSTINCT
Results
Department of Emergency Medicine
ECASS 2
Category
Total ICH
Identified on
review
Parenchymal
Hemorrhage
Type 2 (PH2)
n 63 17
%
n/462
13.6% 3.7%
95% CI 10.8 – 17.1 2.3- 5.9
ECASS 2
Category
Total ICH
Identified on
review
Parenchymal
Hemorrhage
Type 2 (PH2)
n 161 22
%
n/464
37.4% 4.7%
95% CI 30.5– 39.1 3.1 – 7.1
Pooled Analysis
Cohort Results
(Scott et al, 2013)

12. INSTINCT
Results
Department of Emergency Medicine
ECASS 2
Category
Total ICH
Identified on
review
Parenchymal
Hemorrhage
Type 2 (PH2)
n 63 17
%
n/462
13.6% 3.7%
95% CI 10.8 – 17.1 2.3- 5.9
ECASS 2
Category
Total ICH
Identified on
review
Parenchymal
Hemorrhage
Type 2 (PH2)
n 161 22
%
n/464
37.4% 4.7%
95% CI 30.5– 39.1 3.1 – 7.1
Pooled Analysis
Cohort Results
There was no difference in the PH2 rate between INSTINCT Community Hospitals and
Pooled Analysis Cohort Hospitals
Absolute Difference: 1 %
95% CI: 1.6 - 3.8
p = 0.42
(Scott et al, 2013)

13. Conclusion
• The overall ICH rate was lower in community hospitals
participating in the INSTINCT trial compared to pooled
analysis hospitals from NINDS, ECASS, ATLANTIS and
EPITHET trials
.
• The incidence of PH2 in hospitals in participating in the
INSTINCT trial was not different from rates reported in large
clinical research trials of IV thrombolysis.
• Confidence intervals are narrow supporting the safety of
community treatment of stroke
Department of Emergency Medicine

14. References
Department of Emergency Medicine
•Berger C et al. Hemorrhagic Transformation of Ischemic Brain Tissue. Stroke.
2001; 32: 1330-1335.
•Hacke, Werner, et al. "Randomized double-blind placebo-controlled trial of
thrombolytic therapy with intravenous alteplase in acute ischemic stroke
(ECASS II)." The Lancet 352.9136 (1998): 1245-1251.
•Lees KR et al. Time to treatment with intravenous alteplase and outcome in
stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS and
EPITHET trials. Lancet. 2010; 375: 1695-1703.
•Scott PA et al. A multilevel intervention to increase community hospital use of
alteplase for acute stroke (INSTINCT): a cluster randomized trial. Lancet
Neurol. 2013; 12: 139-148.
•Von Kummer, R. (2002). Cerebral hemorrhage following thrombolysis in
stroke. Update on stroke therapy, 2003, 271-7.

15. Questions?
Department of Emergency Medicine