Intracerebral HemorrhagePhase 3NCT06863558
Reduction of Edema With a Specialized Cocktail for Ultra-early Management in Intracerebral Hemorrhage
A Phase 3 study testing PPA Intervention in people with Intracerebral Hemorrhage, run by Second Affiliated Hospital, Zhejiang University, School of Medicine.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intracerebral Hemorrhage
- What is being tested?
- PPA Intervention
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- No sites listed yet
- Study dates
- 8 May 2025to 30 Jun 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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.
Read the 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
- Being tested
- PPA Intervention
- Medical subject headings
- Cerebral Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PPA InterventionDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| PPA Intervention Group | Experimental | 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) Receives: Drug: PPA Intervention |
| Standard Treatment Group | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 5-7 days post-treatment
Secondary outcomes (6)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 7 days
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.
Measured: 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.
Measured: Up to 90 days post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2025
- Study start8 May 2025 (estimated)
- Primary completion10 Mar 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intracerebral HemorrhageStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06863558
- Sponsor's protocol ID
- RESCUE-ICH
- Status last verified
- Feb 2025
- First submitted
- 3 Mar 2025
- Last updated
- 14 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduction of Edema With a Specialized Cocktail for Ultra-early Management in Intracerebral Hemorrhage
- ClinicalTrials.gov ID
- NCT06863558
- Acronym / sponsor ID
- RESCUE-ICH
- Conditions
- Intracerebral Hemorrhage
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 8 May 2025 (estimated)
- Primary completion
- 10 Mar 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 7 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PPA Intervention Group | Experimental | Drug: PPA InterventionParticipants 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 | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PPA InterventionParticipants 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 Group |
Primary outcome
Change in Cerebral Edema Volume at 5-7 Days
Time frame: Baseline and 5-7 days post-treatment
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.
6 secondary outcomes
90-Day Functional Outcome (Modified Rankin Scale, mRS)
Time frame: 90 days post-treatment
Incidence of Hypotension During the Treatment Period
Time frame: Time Frame: During the 5-day treatment period
Change in Hematoma Volume
Time frame: 5-7 days post-treatment
Need for Decompressive Craniectomy
Time frame: Up to 7 days
Mortality at 90 Days
Time frame: 90 days post-treatment
Incidence of Serious Adverse Events (SAEs)
Time frame: Up to 90 days post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PPA Intervention in people with Intracerebral Hemorrhage, run by Second Affiliated Hospital, Zhejiang University, School of Medicine.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Min Lou, PhD, MD (8613958007213, loumingxc@vip.sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cerebral Edema Volume at 5-7 Days (time frame: Baseline and 5-7 days post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.