StrokeNet Thrombectomy Endovascular Platform (STEP)

ABSTRACT Stroke is the fourth leading cause of disability within the United States. Large vessel occlusion (LVO) subtype of acute ischemic stroke (AIS) is the most devastating among all. Recent pivotal trials demonstrated endovascular thrombectomy (EVT) to be highly beneficial in selected subsets of AIS patients. In the wake of these breakthrough studies, an urgent need exists to assess the benefit of EVT in broader populations that are likely to benefit and determine the limits of this therapy, and to address multiple pressing related issues of management and concomitant therapies, in formal clinical trials. To answer multiple EVT management questions efficiently and concurrently, the NIH StrokeNet National Data Management Center (NDMC) at the Medical University of South Carolina, along with the National Coordinating Center and StrokeNet Thrombectomy Endovascular Platform (STEP) Executive Committee, will develop a robust EVT clinical trial platform within NIH StrokeNet. STEP will be optimized to definitely answer EVT-related questions under an overarching Master Protocol, providing an inferentially integrated framework and shared infrastructure, as a randomized, multi-factorial, Bayesian, adaptive platform trial. The STEP trial team will develop operational cores and scientific advisory groups designed to support three broad categories of trials: expansion of EVT indications, innovative EVT devices and concomitant medical therapies, and novel pre- and early-hospital technologies and systems of care. The foundational STEP Master Protocol will define the largest set of inclusion/exclusion criteria to allow study of all consecutive AIS patients with a visible large or medium intracranial vessel occlusion. It also will outline overall study procedures and terminologies, and the unifying statistical inferential model. As a registry-leveraged trial, STEP will minimize burden on the sites by collecting data using an automated transfer mechanism from existing robust, high-quality national clinical registries. Assessment of distinct interventions will be feasible on the platform concurrently or in tandem, and co-enrollment in multiple interventions and sharing of controls will be allowed to maximize efficiency. Details of a mutually exclusive set of interventions are called Domains. The details of patients eligible for a given domain, details of intervention, rules for randomization and adaptation would subsequently be detailed in domain-specific Appendices to the STEP master protocol. The primary endpoint of the STEP trial is favorable global disability level at 90 days, assessed using utility-weighted analysis of the modified Rankin scale (mRS). The STEP trial will allow most efficient testing of treatment strategies and allow rapid optimization of endovascular treatment landscape and acute stroke care.