Steroid Avoidance, Dexamethasone, and RAGE Inhibition for Perioperative Cerebral Edema Management in High-Grade Gliomas

This study is a randomized Phase II trial because it is designed to evaluate thepreliminary efficacy, safety, and feasibility of steroid avoidance and azeliragon asalternatives to dexamethasone for perioperative cerebral edema management in high‐gradeglioma. The trial uses an intermediate imaging‐based efficacy endpoint, enrolls a modestsample size, and is intended to identify promising strategies for subsequent confirmationin a definitive Phase III study.The trial compares three perioperative strategies‐standard dexamethasone, completesteroid avoidance, and RAGE inhibition with azeliragon‐to determine their relative safetyand effectiveness in controlling cerebral edema following tumor resection. In addition toedema control, the study evaluates clinical, functional, and immunologic outcomesassociated with perioperative corticosteroid exposure.Despite widespread use, dexamethasone lacks prospective evidence defining its optimalperioperative role in glioma patients. This study addresses that gap by rigorouslyevaluating steroid avoidance and a mechanistically targeted alternative, with the goal ofimproving patient outcomes while minimizing treatment‐related toxicity.