EPITHET: Positive Result After Reanalysis Using Baseline Diffusion-Weighted Imaging/Perfusion-Weighted Imaging Co-Registration.
OBJECTIVE
the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a prospective, randomized, double-blinded, placebo-controlled, phase II trial of alteplase between 3 and 6 hours after stroke onset. The primary outcome of infarct growth attenuation on MRI with alteplase in mismatch patients was negative when mismatch volumes were assessed volumetrically, without coregistration, which underestimates mismatch volumes. We hypothesized that assessing the extent of mismatch by coregistration of perfusion and diffusion MRI maps may more accurately allow the effects of alteplase vs placebo to be evaluated.


METHODS
patients were classified as having mismatch if perfusion-weighted imaging divided by coregistered diffusion-weighted imaging volume ratio was >1.2 and total coregistered mismatch volume was ≥ 10 mL. The primary outcome was a comparison of infarct growth in alteplase vs placebo patients with coregistered mismatch.


RESULTS
of 99 patients with baseline diffusion-weighted imaging and perfusion-weighted imaging, coregistration of both images was possible in 95 patients. Coregistered mismatch was present in 93% (88/95) compared to 85% (81/95) with standard volumetric mismatch. In the coregistered mismatch patients, of whom 45 received alteplase and 43 received placebo, the primary outcome measure of geometric mean infarct growth was significantly attenuated by a ratio of 0.58 with alteplase compared to placebo (1.02 vs 1.77; 95% CI, 0.33-0.99; P=0.0459).


CONCLUSIONS
when using coregistration techniques to determine the presence of mismatch at study entry, alteplase significantly attenuated infarct growth. This highlights the necessity for a randomized, placebo-controlled, phase III clinical trial of alteplase using penumbral selection beyond 3 hours.
National Stroke Research Institute, University of Melbourne, Australia.
Yoshinari
Y
Nagakane
Soren
S
Christensen
Caspar
C
Brekenfeld
Henry
H
Ma
Leonid
L
Churilov
Mark W
MW
Parsons
Christopher R
CR
Levi
Kenneth S
KS
Butcher
Andre
A
Peeters
P Alan
PA
Barber
Christopher F
CF
Bladin
Deidre A
DA
De Silva
John
J
Fink
Thomas E
TE
Kimber
David W
DW
Schultz
Keith W
KW
Muir
Brian M
BM
Tress
Patricia M
PM
Desmond
Stephen M
SM
Davis
Geoffrey A
GA
Donnan
D000368:Aged; D000369:Aged, 80 and over; D020520:Brain Infarction / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011859:Radiography; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator