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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Drug: PPA Intervention

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.

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Min Lou, PhD, MD; Phone Number: 8613958007213; Email: loumingxc@vip.sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Clinical diagnosis of supratentorial intracerebral hemorrhage (ICH)
• Symptom onset within 3 days (≤72 hours) before randomization
• Baseline CT-confirmed hematoma volume ≥3 mL
• Not scheduled for hematoma evacuation surgery (either not indicated or declined by the patient/family)
• Written informed consent obtained from the patient or legally authorized representative

Exclusion Criteria:

• Baseline 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 pose a high safety risk (e.g., end-stage organ failure, advanced malignancy)
• Presence of secondary causes of ICH (e.g., arteriovenous malformation, aneurysm rupture, hemorrhagic transformation of ischemic stroke)
• Pregnancy or lactation
• Participation in another interventional trial that may influence study outcomes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: 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.
Experimental: 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)	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cerebral Edema Volume at 5-7 Days	The primary outcome of this study is the change in cerebral edema volume, as assessed by non-contrast CT imaging at baseline (pre-treatment) and 5-7 days after treatment initiation. Edema volume will be quantified using standardized imaging analysis techniques. The difference in cerebral edema volume between the PPA intervention group and the standard treatment group will be compared to evaluate the efficacy of the pharmacological cocktail in reducing brain swelling.	Baseline and 5-7 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality at 90 Days	All-cause mortality will be recorded and compared between the PPA intervention and standard treatment groups to evaluate the impact of the intervention on survival.	90 days post-treatment
Incidence of Serious Adverse Events (SAEs)	All serious adverse events (SAEs), including cardiovascular complications, major bleeding, and severe drug reactions, will be recorded and compared between groups.	Up to 90 days post-treatment
Incidence of Hypotension During the Treatment Period	The occurrence of clinically significant hypotension (defined as systolic blood pressure <90 mmHg) will be monitored throughout the intervention period. The frequency, severity, and need for medical intervention will be compared between the two study groups.	Time Frame: During the 5-day treatment period
Change in Hematoma Volume	Assessment of hematoma volume on CT imaging at baseline and 5-7 days post-treatment to evaluate any changes in bleeding size.	5-7 days post-treatment
Need for Decompressive Craniectomy	The proportion of patients who require decompressive craniectomy due to increased intracranial pressure or neurological deterioration.	Up to 7 days
90-Day Functional Outcome (Modified Rankin Scale, mRS)	Functional outcomes will be assessed using the modified Rankin Scale (mRS) at 90 days post-treatment, mRS: minimum value = 0, maximum value = 6, and lower scores mean a better outcome	90 days post-treatment

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): May 8, 2025
• Primary Completion (Estimated): March 10, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: March 3, 2025
• First Posted (Actual): March 7, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 11, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: RESCUE-ICH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No