PICASSO (Proximal Internal Carotid Artery Acute Stroke Secondary to Tandem Lesion or Local Occlusion)  Thrombectomy Randomized Trial: Study Protocol and Rationale.

Background: The optimal treatment of acute large vessel occlusion with concomitant extracranial steno-occlusive disease of the internal carotid artery remains unclear. The PICASSO (Proximal Internal Carotid Artery Acute Stroke Secondary to Tandem or Local Occlusion Thrombectomy Trial) randomized clinical trial is designed to answer the question whether acute carotid stenting is superior to a nonacute stenting approach in the setting of a tandem lesion or tandem occlusion. Methods: PICASSO is a prospective, randomized, controlled, multicenter, open label, assessor-blinded acute ischemic stroke trial with pragmatic design enrolling up to 404 patients at up to 60 sites. Patients with anterior circulation large vessel occlusion with severe stenosis or complete occlusion (70%-100%) of the extracranial carotid artery who meet the imaging and clinical eligibility criteria will be randomized in a 1:1 ratio to undergo mechanical thrombectomy of the intracranial lesion plus emergent stenting of the extracranial lesion versus mechanical thrombectomy plus no stenting up to 16 hours from last known well. Results: The primary efficacy outcome is the ordinal shift of 90-day modified Rankin Scale (mRS) score. The primary analysis will be based on the intention-to-treat principle stratified by the Alberta Stroke Program Early CT [Computed Tomography] Score (7-8 versus 9-10), degree of proximal carotid stenosis (70%-90% versus 91%-100%), NIHSS (≤ 10 versus > 10), and use of intravenous thrombolysis. The primary safety outcome is symptomatic intracranial hemorrhage. Secondary outcomes include 1-year mRS (dichotomized and ordinal), successful reperfusion, and vessel patency at follow-up. Subgroup analyses will include comparison of intravenous versus oral antiplatelets in the stenting arm, and treatment of proximal intracranial occlusion first versus a simultaneous approach. Conclusion: PICASSO is a pragmatic randomized trial, designed to address the safety and efficacy of mechanical thrombectomy with acute carotid stenting versus nonacute stenting with or without delayed revascularization treatment in patients with anterior circulation large vessel occlusion and concomitant extracranial severe stenosis or complete occlusion. Clinical Trial Registration: NCT05611242.