This trial has been designed with subject safety in mind, as a seamless Phase II (feasibility) / Phase III (pivotal) adaptive design, in order to address the concerns around potential unknown harms to enrolled subjects. This study will help to answer the question of whether carefully selecting subjects by using Clinical Imaging Mismatch will allow acute ischemic stroke patients who present at or beyond 6 hours from Time Last Seen Well (TLSW) to be considered for intra-arterial intervention. If Trevo thrombectomy plus medical management leads to better clinical outcomes over medical management alone, more patients in the future could receive endovascular treatment (either in addition to or in lieu of IV tPA).