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

NCT ID: NCT06863571

Last Updated: 2025-04-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-12
• Study Completion Date: 2026-06-30

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

PPA Intervention Group

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)

Group Type: EXPERIMENTAL

PPA Intervention

Intervention Type: DRUG

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)

Standard Treatment Group

Participants in this group will receive standard medical treatment for acute ischemic stroke without the PPA intervention. This includes appropriate supportive care, blood pressure management according to clinical guidelines, and symptomatic treatment as required.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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)

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Second Affiliated Hospital of Zhejiang University, School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Min Lou, PhD, MD

Role: CONTACT

loumingxc@vip.sina.com

8613958007213

Facility Contacts

Min Lou

Role: primary

Other Identifiers

RESCUE-IS

Identifier Type: -

Identifier Source: org_study_id