NCT06863571

Reduction of Edema With a Specialized Cocktail for Ultra-early Management in Ischemic Stroke

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 68 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Large ischemic stroke is a severe subtype of acute ischemic stroke (AIS), often leading to malignant cerebral edema, elevated intracranial pressure, and poor functional outcomes. Despite early aggressive treatment, malignant cerebral edema remains a major determinant of prognosis, even in cases of successful recanalization. Preclinical studies suggest that a pharmacological cocktail (PPA) may alleviate cerebral edema by modulating extracellular potassium balance, maintaining aquaporin-4 expression, and enhancing lymphatic drainage. This multicenter, randomized controlled trial (RCT) aims to assess the safety and efficacy of PPA in reducing cerebral edema and improving outcomes in patients with large ischemic stroke. The study will enroll 68 patients with MCA-territory infarction (80-300 mL infarct volume or ASPECTS 1-5), who are not undergoing decompressive craniectomy. Participants will be randomized to receive PPA therapy or standard treatment. The primary outcome is cerebral edema at 5-7 days, with secondary outcomes including 90-day functional outcomes (mRS) and safety assessments.

Detailed description

Large ischemic stroke is a severe subtype of acute ischemic stroke (AIS), often leading to malignant cerebral edema, elevated intracranial pressure (ICP), and poor functional outcomes. Despite early aggressive treatment, malignant cerebral edema remains a major determinant of prognosis, even in cases of successful recanalization. Patients without endovascular therapy (EVT) also face significant risks of cerebral edema and intracranial hypertension, which contribute to high morbidity and mortality. Preclinical studies suggest that a pharmacological cocktail (PPA) may alleviate cerebral edema by modulating extracellular potassium balance, maintaining aquaporin-4 expression, and enhancing lymphatic drainage. In ischemic stroke models, PPA has demonstrated the potential to accelerate potassium homeostasis and mitigate edema formation, while in traumatic brain injury models, PPA has been shown to promote lymphatic clearance and reduce brain swelling. This multicenter, randomized controlled trial (RCT) aims to evaluate the safety and efficacy of PPA in reducing cerebral edema in patients with large ischemic stroke. A total of 68 patients with MCA-territory infarction (80-300 mL infarct volume or ASPECTS 1-5) who are not undergoing decompressive craniectomy will be enrolled and randomly assigned to receive PPA therapy or standard treatment in a 1:1 ratio. The primary endpoint is cerebral edema at 5-7 days, assessed by follow-up imaging. Secondary endpoints include functional outcomes at 90 days (mRS) and safety assessments, including adverse events such as hypotension and intracranial hypertension. The study intervention consists of a PPA regimen over five days, including terazosin or urapidil, and propranolol or esmolol, with individualized blood pressure management based on recanalization status. Imaging and safety monitoring will be conducted throughout the study, and adverse events will be closely tracked and analyzed quarterly. To ensure ethical compliance, informed consent will be obtained from patients or their legally authorized representatives, with mechanisms in place for reconfirmation if the patient regains decision-making capacity. This trial seeks to establish a novel pharmacological approach for cerebral edema management, with the ultimate goal of improving neurological outcomes in large ischemic stroke patients.

Conditions

• Ischemic Stroke

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: 2025-04-12
• Primary completion: 2026-03-10
• Completion: 2026-06-30
• First posted: 2025-03-07
• Last updated: 2025-04-18

Locations

1 site across 1 country: China