Rapid Local Ischemic Postconditioning in Acute Ischemic Stroke (RAPID-SAVE)

A Multicenter, Open Label, Blind Endpoint, Clinical Trial to Evaluate the Efficacy and Safety of Rapid Local Ischemic Postconditioning in Acute Ischemic Stroke Patients Received Successful Thrombectomy Reperfusion

The objective of this clinical trial is to determine whether rapid local ischemic postconditioning (RL-IPostC) is effective in preventing brain edema and safe in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy. In this trial, researchers will block antegrade cerebral blood flow temporarily by the way of balloon inflation/deflation in AIS patients immediately after revascularization. It makes the ischemic reperfusion brain tissue have a capacity of adaptation through intermittent blood flow restoration. Researchers will evaluate the protective role and safety of different duration of balloon inflation/deflation. The optimal postconditioning intervention dose will be determined for further confirmative investigation.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke; Brain Edema; Mechanical Thrombectomy; Ischemic Postconditioning
• Intervention / Treatment: Procedure: rapid local ischemic postconditioning

Detailed Description

This will be an umbrella trial of testing the efficacy and safety of three postconditioning intervention doses. It will be a prospective, open-label, blinded endpoint, three-dose Bayesian Optimal Phase 2(BOP2) design trial with interim efficacy and safety monitoring. The maximum number of subjects for this trial is estimated as 135 patients. Eligible patients are 18 years or older with symptomatic large vessel occluded (LVO) AIS treated with mechanical thrombectomy (MT) achieving successful reperfusion defined as mTICI score 2b or 3. Patients will receive 5 cycles of balloon inflation/deflation at ipsilateral C1 segment of internal carotid artery (ICA) for the temporary occlusion of the restoration of antegrade blood flow. Three postconditioning intervention doses of 30s/30s, 60s/60s and 180s/180s were adopted for block and restore of blood blow. The primary outcome is a favorable binary outcome defined as no clinically meaningful brain swelling from baseline to 24 hours and no clinically meaningful infarction growth from baseline to 24 hours and no causally attributable serious adverse events (SAEs). It's a composite outcome of efficacy and safety outcome. Key secondary outcomes include efficacy outcome indicating no clinically meaningful brain swelling defined by cerebral spinal fluid (CSF) volume reduction≤5 mL from baseline to 24 hours and safety outcome indicating infarct volume growth>10 mL from baseline to 24 hours or causally attributable SAEs. Other secondary outcomes include change of brain net water uptake, midline shift and functional outcome. For each intervention dose, we will perform the interim analyses following pre-defined optimized Bayesian rule for early stopping to make a go/no-go decision when the number of enrolled patients reaches 10, 20, 30. The optimal intervention dose will be determined according to the number of patients reach the primary endpoints in different groups.

• Study Type: Interventional
• Enrollment (Estimated): 135
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yueqi Zhu, MD; Phone Number: 0086-21-64844183; Email: zhuyueqi@hotmail.com
• Study Contact Backup: Name: Jiangshan Deng, MD; Phone Number: 0086-21-24058404; Email: johnson120@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years old
2. Presenting with symptoms consistent with acute ischemic stroke
3. Pre-stroke mRS score 0-1
4. Baseline NIHSS score≥6
5. Endovascular treatment can be initiated (femoral puncture) within 24 hours from stroke onset (stroke onset time is defined as last known well time)
6. Occlusion of the intracranial internal carotid artery, or the middle cerebral artery(M1 or M2) confirmed by CTA or MRA, and is the culprit artery
7. Alberta Stroke Program Early CT Score (ASPECTS) (based on non-contrast CT) >5 on noncontrast computed tomography (NCCT) for stroke onset time less than 6 hours, infarct Core < 70 ml (defined as rCBF <30% on CT perfusion) and mismatch ratio > 1.2 (penumbra defined as Tmax >6 seconds volume) for stroke onset time between 6 and 24 hours.
8. Embolism verified as the etiology of occluded artery and mTICI 2b or 3 regained after mechanical thrombectomy
9. Informed consent signed

Exclusion Criteria:

1. Stenosis of the proximal middle cerebral artery, internal carotid artery, or common carotid artery (≥50%) of the culprit artery
2. Multiple vascular embolism on different pathways (not refers to the ipsilateral middle artery and anterior artery)
3. Pre ischemic stroke or transient ischemic attack within past 3 months
4. The expected survival time is less than 6 months, could not be followed at 90 days (such as patient with malignant tumor)
5. Currently pregnant, mental disease, advanced hepatic and renal insufficiency, severe heart failure
6. Participation in other interventional randomized clinical trials that may confound the outcome assessment of the trial
7. Other circumstances that the investigator considers inappropriate for this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: RL-IPostC 30; The RL-IPostC 30 protocol involved 5 cycles of blow block and restoration, each for 30 seconds.	Procedure: rapid local ischemic postconditioning; Rapid local ischemic postconditioning (RL-IPostC) is performed immediately (within 5 minutes) after revascularization. A balloon guiding catheter (BGC) positioned on ipsilateral C1 segment of internal carotid artery is inflated and deflated for the temporary occlusion of the antegrade flow.
Other: RL-IPostC 60; The RL-IPostC 60 protocol involved 5 cycles of blow block and restoration, each for 60 seconds.	Procedure: rapid local ischemic postconditioning; Rapid local ischemic postconditioning (RL-IPostC) is performed immediately (within 5 minutes) after revascularization. A balloon guiding catheter (BGC) positioned on ipsilateral C1 segment of internal carotid artery is inflated and deflated for the temporary occlusion of the antegrade flow.
Other: RL-IPostC 180; The RL-IPostC 180 protocol involved 5 cycles of blow block and restoration, each for 180 seconds.	Procedure: rapid local ischemic postconditioning; Rapid local ischemic postconditioning (RL-IPostC) is performed immediately (within 5 minutes) after revascularization. A balloon guiding catheter (BGC) positioned on ipsilateral C1 segment of internal carotid artery is inflated and deflated for the temporary occlusion of the antegrade flow.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants without clinically meaningful cerebral swelling, significant increase in infarct volume from baseline and intervention-related serious adverse events.	No clinically meaningful cerebral swelling defined as volume reduction of cerebrospinal fluid ≤ 5 mL from baseline. No significant increase in infarct volume from baseline defined as an increase in infarct volume of ≤ 10 mL. Intervention-related serious adverse events defined as SAEs specifically related to RL-IPostC other than mechanical thrombectomy.	24 hours after procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of participants without clinically meaningful cerebral swelling	No clinically meaningful brain swelling defined by CSF volume reduction≤5 mL from baseline to 24 hours.	24 hours after procedure
Rate of participants with significant increase in infarct volume from baseline or intervention-related serious adverse events.	Significant increase in infarct volume from baseline defined as an increase in infarct volume of more than 10 mL. Intervention-related serious adverse events defined as SAEs specifically related to RL-IPostC other than mechanical thrombectomy.	24 hours after procedure
Change in volume of cerebrospinal fluid (∆CSF72) at 72 hours	Change in volume of cerebrospinal fluid (∆CSF72) at 72 hours from baseline	72 hours after procedure
Change of net water uptake (∆NWU24) at 24 hours	Change of net water uptake (∆NWU24) at 24 hours from baseline	24 hours after procedure
Change of net water uptake (∆NWU72) at 72 hours	Change of net water uptake (∆NWU72) at 72 hours from baseline	72 hours after procedure
Midline shift at 24 hours	Distance of midline shift at 24 hours (in millimeters at the level of the septum pellucidum)	24 hours after procedure
Midline shift at 72 hours	Distance of midline shift at 72 hours (in millimeters at the level of the septum pellucidum)	72 hours after procedure
Change of NIHSS at 24 hours	Change of NIHSS at 24 hours from baseline	24 hours after procedure
Early therapeutic response to treatment	Decrease in the NIHSS score of ≥8 from baseline or an NIHSS score of 0 to 2 at 24 hours)	24 hours after procedure
Good outcome at 90 days	Proportion of mRS score of 0 to 2 at 90 days	90 days after procedure
Excellent outcome at 90 days	Proportion of mRS score of 0 to 1 at 90 days	90 days after procedure

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University Affiliated Sixth People's Hospital
• Collaborators: First People's Hospital of Hangzhou; RenJi Hospital; Shanghai East Hospital; Zhangzhou Municipal Hospital of Fujian Province
• Investigators: Principal Investigator: Yueqi Zhu, MD, Shanghai Jiao Tong University Affiliated Sixth People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2024
• Primary Completion (Estimated): June 15, 2025
• Study Completion (Estimated): September 15, 2025

Study Registration Dates

• First Submitted: March 4, 2024
• First Submitted That Met QC Criteria: March 9, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 9, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Brain Edema
• Other Study ID Numbers: RAPID-SAVE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No