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

Inclusion Criteria:

Age ≥18 years at the time of screening

* Newly diagnosed supratentorial tumor with imaging characteristics consistent with high-grade glioma
* Candidate for craniotomy with planned resection of more than 50% of the contrast-enhancing tumor
* Midline shift ≤10 mm on preoperative imaging
* Limited pre-enrollment corticosteroid exposure (≤10 mg dexamethasone total and no chronic steroid use within 30 days)
* Karnofsky Performance Status ≥60
* Adequate organ function to undergo surgery and postoperative care as determined by the investigator
* Ability to provide informed consent and comply with study procedures
* Agreement to use effective contraception, when applicable

Exclusion Criteria:

* Participants meeting any of the following will be excluded:

  * Imaging or clinical features highly suggestive of primary CNS lymphoma or metastatic disease
  * Posterior fossa tumors or lesions associated with high risk of brainstem compression
  * Leptomeningeal or widely disseminated disease
  * Clinical conditions requiring immediate corticosteroid therapy
  * Prior exposure to high-dose corticosteroids (\>10 mg dexamethasone) or chronic steroid use within 30 days
  * Active systemic illness that increases surgical risk, including uncontrolled infection, coagulopathy, or severe cardiopulmonary disease
  * Pregnancy or breastfeeding
  * Known immunodeficiency or chronic infection requiring immunosuppressive therapy
  * Use of investigational agents within 30 days or concurrent use of immunosuppressive medications not permitted by protocol
  * Known hypersensitivity to azeliragon
  * Inability to undergo MRI due to contraindications such as incompatible implants or severe claustrophobia
  * Life expectancy less than 3 months as determined by the investigator
  * Participation in another interventional clinical trial prior to initiation of standard adjuvant therapy Vulnerable Populations: This study will not enroll children, pregnant or breastfeeding individuals, or prisoners. Individuals with impaired decision-making capacity may be enrolled only when a legally authorized representative is available to provide consent in accordance with institutional and regulatory requirements.