Question special
Resident

Congratulations to the authors on presentation of this important study of extending thrombolysis upto 9 hours for patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. Re-pefusion based on tissue based approach rather than a time based approach offers a much more objective assessment.

I had two questions:
1. Do you think the benefit of improved primary outcome of score of 0 or 1 on modified Rankin scale at 90 days (adjusted risk ratio 1.44) outweighs the harms of symptomatic intracranial hemorrhage (adjusted risk ratio 7.22). Especially as there was no significant difference in the secondary outcome of functional improvement. And do you think the risks of intracranial hemorrhage would have been higher if more patients were recruited as had been initially planned?

2. My second question is about the premature termination of the trial. As the authors conclude, this is one of the limitations of the trial. The authors mention, as does the accompanying editorial, that the WAKE UP trial was not truly equivalent to the EXTEND trial as it targeted patients who were likely to be eligible for thrombolysis at the standard times and did not use penumbra based image guidance. Given the difference in patient population, imaging selection and severity of stroke would it not have been appropriate to complete the trial as was originally planned?