RECRUITINGPhase 3INTERVENTIONAL

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

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - Age ≥18 years - Clinical diagnosis of acute ischemic stroke (AIS) in the middle cerebral artery (MCA) territory - Symptom onset within 3 days (≤72 hours) before randomization - Infarct volume of 80-300 mL or ASPECTS 1-5 involving at least two cortical regions - Not scheduled for decompressive craniectomy (either not indicated or declined by the patient/family) - Written willing to sign a consent form obtained from the patient or legally authorized representative Who Should NOT Join This Trial: - Baseline evidence of brain herniation or severe hypotension (SBP \<90 mmHg) - Contraindications to PPA medications (terazosin, urapidil, esmolol, propranolol), such as asthma or severe bradycardia - Severe comorbidities that may interfere with efficacy assessment or safety monitoring (e.g., end-stage organ failure, advanced malignancy) - Pregnancy or lactation - Participation in another interventional trial that may influence study outcomes Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Age ≥18 years * Clinical diagnosis of acute ischemic stroke (AIS) in the middle cerebral artery (MCA) territory * Symptom onset within 3 days (≤72 hours) before randomization * Infarct volume of 80-300 mL or ASPECTS 1-5 involving at least two cortical regions * Not scheduled for decompressive craniectomy (either not indicated or declined by the patient/family) * Written informed consent obtained from the patient or legally authorized representative Exclusion Criteria: * Baseline evidence of brain herniation or severe hypotension (SBP \<90 mmHg) * Contraindications to PPA medications (terazosin, urapidil, esmolol, propranolol), such as asthma or severe bradycardia * Severe comorbidities that may interfere with efficacy assessment or safety monitoring (e.g., end-stage organ failure, advanced malignancy) * Pregnancy or lactation * Participation in another interventional trial that may influence study outcomes

Treatments Being Tested

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)

Locations (1)

Second Affiliated Hospital of Zhejiang University, School of Medicine

Hangzhou, Zhejiang, China