Ischemic StrokePhase 3NCT06863571
Reduction of Edema With a Specialized Cocktail for Ultra-early Management in Ischemic Stroke
A Phase 3 study testing PPA Intervention in people with Ischemic Stroke, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke
- 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
- 68 participants
- Where
- 1 siteChina
- Study dates
- 12 Apr 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 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Second Affiliated Hospital of Zhejiang University, School of Medicine
Hangzhou, Zhejiang, 310000
Min Lou
About this study
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.
Read the 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
- Being tested
- PPA Intervention
- Medical subject headings
- Ischemic Stroke
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.
Cerebral Edema at 5-7 Days
The primary outcome of this study is cerebral edema. Edema will be quantified using standardized imaging analysis techniques. The difference in cerebral edema 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: 5-7 days post-treatment
Secondary outcomes (5)
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: During the 5-day treatment period
Need for Decompressive Craniectomy
The proportion of patients who require decompressive craniectomy (DC) due to worsening cerebral edema and refractory intracranial hypertension will be recorded and compared between the study groups. This will serve as an indicator of treatment efficacy in preventing severe brain swelling.
Measured: Up to 7 days post-treatment
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 start12 Apr 2025
- 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 Ischemic StrokeStudies 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
- 68 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06863571
- Sponsor's protocol ID
- RESCUE-IS
- Status last verified
- Feb 2025
- First submitted
- 3 Mar 2025
- Last updated
- 18 Apr 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 18 Apr 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 Ischemic Stroke
- ClinicalTrials.gov ID
- NCT06863571
- Acronym / sponsor ID
- RESCUE-IS
- Conditions
- Ischemic Stroke
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 12 Apr 2025 (actual)
- 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.
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.
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 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)
Key exclusion criteria (5 listed)
- 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
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
Cerebral Edema at 5-7 Days
Time frame: 5-7 days post-treatment
The primary outcome of this study is cerebral edema. Edema will be quantified using standardized imaging analysis techniques. The difference in cerebral edema 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.
5 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: During the 5-day treatment period
Need for Decompressive Craniectomy
Time frame: Up to 7 days post-treatment
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 18 Apr 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PPA Intervention in people with Ischemic Stroke, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
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 5 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: looking for participants now, as of the sponsor's last update on 18 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Cerebral Edema at 5-7 Days (time frame: 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 18 Apr 2025.