Statistical Analysis Plan for EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) trial

Abstract

Background: EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) is a randomized, multicenter, double-blinded, placebo-controlled phase 3 trial to test the hypothesis of extending the thrombolysis time window to 9 h from stroke onset and in wake-up stroke (WUS) patients.

Objective: To formulate the detailed statistical analysis plan for the EXTEND trial prior to database lock. This statistical analysis plan is based on the published and registered EXTEND trial protocol and is developed by the blinded steering committee and management team.

Results: The developed EXTEND statistical analysis plan is transparent, verifiable, and predetermined before the database lock. It is consistent with reporting standards for clinical trials and provides for clear and open reporting.

Conclusions: Publication of a statistical analysis plan serves to reduce potential trial analysis and reporting bias and outlines pre-specified analyses to quantify the benefits and harms of extending the thrombolysis time window to 9 h from stroke onset and in wake-up stroke patients. Trial registration: ClinicalTrials.gov number NCT00887328 registered 23/Apr/2009 and NCT01580839 (EXTEND International) registered 19/Apr/2012.

Keywords: alteplase; computed tomography perfusion imaging; ischemic stroke; penumbral mismatch; randomised trial; thrombolysis; thrombolytic therapy; time window; wake-up stroke.