STEP is a Randomized, Multifactorial, Adaptive Platform trial that seeks to optimize the care of patients with acute ischemic stroke (AIS) due to large or medium vessel occlusions (LVOs and MVOs). This Master Protocol describes trial procedures, data collection, data monitoring, follow-up visits, and safety procedures that will be employed in all Domain-Specific Appendices.

STEP is a registry-based trial; it uses data from existing registries to record information for a subset of the trial Case Report Form (CRF). Additional registry data from non-randomized STEP patients may be used for trial screening, planning, and generalizability assessment purposes.

In the Master Protocol we define the general outcomes of interest. Individual domains may define additional endpoints of interest.

Clinical Efficacy Measures

• 90 (+/-15)-day global disability assessed with the modified Rankin Scale
• Global disability assessed with the modified Rankin Scale at discharge
• Neurologic deficit [NIH Stroke Scale (NIHSS)], at 24 (+/-12) hours

Safety Endpoint Measures

The following safety endpoints will be analyzed in both EVT and MM patients:

• Symptomatic intracranial hemorrhage within 36 hours of randomization
• Any radiologic intracranial hemorrhage within 36 hours of randomization
• Mortality by 90 (+/-15) days
• Serious adverse events within 90 (+/-15) days

Additional trial-specific protocol endpoints may be defined in individual Domain-Specific Appendices and will only be collected in individuals enrolled in those particular domains.