There have been myriad attempts to establish the efficacy of pharmacological and nonpharmacological interventions with putative neuroprotective action in acute stroke that have failed when tested in human clinical trials. Since the 2013 AIS Guidelines, there have been several more trials testing putative neuroprotective agents that have been negative. The FAST-MAG trial (Field Administration of Stroke Therapy Magnesium) of prehospital magnesium infusion was the first acute stroke neuroprotection drug trial to enroll participants during ambulance transport, but no differences were seen between the intervention group and placebo control subjects.235 The ALIAS trials parts I and II failed to show the efficacy of IV albumin infusion in AIS.232,233 See Table LII in online Data Supplement 1. 3.13. Emergency Carotid Endarterectomy Carotid Angioplasty and Stenting Without Intracranial Clot 3.13. Emergency Carotid Endarterectomy/Carotid Angioplasty and Stenting Without Intracranial Clot COR LOE New, Revised, or Unchanged The usefulness of emergent or urgent carotid endarterectomy (CEA)/carotid angioplasty and stenting when clinical indicators or brain imaging suggests a small infarct core with large territory at risk (eg, penumbra), compromised by inadequate flow from a critical carotid stenosis or occlusion, or in the case of acute neurological deficit after CEA, in which acute thrombosis of the surgical site is suspected, is not well established. IIb B-NR Recommendation reworded for clarity from 2013 AIS Guidelines. COR unchanged. LOE amended to conform with the ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. In patients with unstable neurological status (eg, stroke-in-evolution), the efficacy of emergency or urgent CEA /carotid angioplasty and stenting is not well established. IIb B-NR Recommendation reworded for clarity from 2013 AIS Guidelines. COR unchanged. LOE amended to conform with the ACC/AHA 2015 Recommendation Classification System. See Table XCV in online Data Supplement 1 for original wording. 3.14. 