We thank Drs Broderick and Tomsick for their insights regarding our editorial ‘The tribulations of stroke trials’.¹ As the title of the editorial implies, acute stroke trials are difficult to design and complete. Our editorial was not meant to discount the results of the Interventional Management of Stroke III (IMS III), or those of the Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR-RESCUE) and SYNTHESIS Expansion trials, but rather to temper the interpretation of the results and to emphasize potentially confounding methodological nuances that should be examined prior to designing future stroke trials.

In the first paragraph of their letter, Broderick and Tomsick refer to IMS III as a ‘failed’ endovascular stroke trial. With regard to the pre-trial hypothesis that the combination of a partial dose of tissue plasminogen activator (tPA) and endovascular therapy …