NCT06863558

Reduction of Edema With a Specialized Cocktail for Ultra-early Management in Intracerebral Hemorrhage

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 58 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Intracerebral hemorrhage (ICH) is a severe stroke subtype with high mortality and disability rates, often worsened by perihematomal edema (PHE), which increases intracranial pressure and leads to poor outcomes. Preclinical studies suggest that a pharmacological cocktail (PPA) may help reduce cerebral edema by modulating potassium balance, preserving aquaporin-4 expression, and enhancing lymphatic drainage. This multicenter, randomized controlled trial (RCT) aims to evaluate the safety and efficacy of PPA in ICH patients. A total of 58 patients with supratentorial ICH (≥3 mL hematoma volume) who are not undergoing surgical evacuation will be randomized to receive either PPA therapy or standard treatment. The primary outcome is the change in cerebral edema volume at 5-7 days, assessed by CT imaging. Secondary outcomes include 90-day functional outcomes (mRS), need for decompressive craniectomy, and safety assessments. This study seeks to explore PPA as a potential treatment strategy for cerebral edema in ICH patients.

Detailed description

Intracerebral hemorrhage (ICH) is a severe subtype of stroke, accounting for 15-20% of all strokes. Compared to ischemic stroke, ICH has a higher mortality and disability rate, with its incidence steadily rising worldwide, imposing a substantial burden on families and healthcare systems. A key factor contributing to poor prognosis in ICH is perihematomal edema (PHE), which rapidly progresses during the acute phase, leading to increased intracranial pressure (ICP), brain tissue displacement, and potential brain herniation. Even in patients who survive the acute phase, persistent cerebral edema can cause long-term neurological deficits and impair quality of life. Therefore, effective management of cerebral edema is critical for improving outcomes in ICH patients. Preclinical studies suggest that a pharmacological cocktail (PPA), consisting of adrenergic antagonists, may help reduce cerebral edema by modulating extracellular potassium homeostasis, maintaining aquaporin-4 (AQP-4) expression, and enhancing lymphatic drainage. In both traumatic brain injury and ischemic stroke models, PPA has shown potential in alleviating cerebral edema and improving neurological recovery. Based on these findings, this multicenter, randomized controlled trial (RCT) aims to evaluate the safety and efficacy of PPA in reducing cerebral edema in ICH patients. The study will enroll 58 patients diagnosed with supratentorial ICH (≥3 mL hematoma volume) who are not undergoing surgical evacuation. Participants will be randomly assigned to receive PPA therapy or standard treatment. The primary outcome is change in cerebral edema volume at 5-7 days, assessed by CT imaging. Secondary outcomes include functional outcomes at 90 days (mRS), need for decompressive craniectomy, incidence of hypotension, and adverse events. This study aims to explore PPA as a novel pharmacological approach for managing cerebral edema in ICH, potentially improving patient prognosis and clinical outcomes.

Conditions

• Intracerebral Hemorrhage

Interventions

Type	Name	Description
DRUG	PPA Intervention	Participants in this group will receive a pharmacological cocktail (PPA) for five days in addition to standard medical treatment for acute ischemic stroke. The regimen includes terazosin or urapidil, and propranolol or esmolol, with individualized blood pressure management. The specific protocol is as follows: * Terazosin (no less than 1 mg orally or via nasogastric tube, nightly) or Urapidil (100 mg in 30 mL saline, IV infusion at no less than 2 mL/h) * Propranolol (10 mg orally or via nasogastric tube, three times daily) or Esmolol (1 g in 40 mL saline, IV infusion at no less than 2 mL/h; use for no more than 48 hours. Beyond 48 hours, switch to Propranolol)

Timeline

• Start date: 2025-05-08
• Primary completion: 2026-03-10
• Completion: 2026-06-30
• First posted: 2025-03-07
• Last updated: 2025-05-14