Effectiveness and Biological Mechanism of Direct Ischemic Post-conditioning for Acute Stroke Patients Due to Large Vessel Occlusion

Effectiveness and Biological Mechanism of Direct Ischemic Post-conditioning for Acute Stroke Patients Due to Large Vessel Occlusion: A Randomized Controlled Pilot Trial

The goal of this clinical trial is to determine if direct ischemic post-conditioning (IPostC) can alleviate ischemic-reperfusion injury (I/R) in patients who have undergone endovascular thrombectomy (EVT). Additionally, the study aims to explore the underlying mechanisms of direct IPostC.

The primary questions this trial seeks to answer are:

1. Is direct IPostC effective for acute stroke patients with large vessel occlusion?
2. What are the underlying mechanisms of direct IPostC?

Participants will be randomly assigned to one of two groups: an EVT alone group or an EVT plus direct IPostC group. Direct IPostC will be administered immediately after EVT through four cycles of mechanical interruptions of reperfusion. We will evaluate outcomes based on final infarct volume, infarct volume growth, clinical parameters, and I/R-related imaging and laboratory biomarkers. Additionally, an exploratory multi-omics analysis will be conducted to uncover the detailed mechanisms of direct IPostC.

Study Overview

• Status: Completed
• Conditions: Stroke, Acute; Neuroprotection; Ischemic Conditioning
• Intervention / Treatment: Procedure: Endovascular therapy; Procedure: Direct Ischemic Post-conditioning

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300070
      • Tianjin Huanhu Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Ischemic stroke confirmed by CT or MRI.
2. Large vessel occlusion confirmed by CTA or MRA, including the intracranial internal 3. carotid artery (ICA) and middle cerebral artery (MCA M1/M2).

4. Recanalization of the occluded vessel at eTICI grade 2b/3, confirmed by DSA after thrombectomy.

5. The patient or legally authorized representative has signed an informed consent form.

Exclusion Criteria:

1. Inability to perform an MRI or CT scan for any reason.
2. Presence of any condition that would interfere with neurological assessment or any psychiatric disorders.
3. Stroke onset accompanied by seizures, resulting in the inability to obtain an accurate NIHSS baseline.
4. Pregnancy.
5. Presence of other serious, advanced, or terminal illnesses.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Endovascular therapy	Procedure: Endovascular therapy; Thrombectomy alone.
Experimental: Endovascular therapy plus direct ischemic post-conditioning	Procedure: Endovascular therapy; Thrombectomy alone.; Procedure: Direct Ischemic Post-conditioning; After thrombectomy, the balloon was inflated to a pressure of no more than 4 atm at the occlusion site to block blood flow for 2 minutes, as confirmed by angiography. The balloon was then deflated, allowing blood flow to resume for 2 minutes. These steps were repeated four times.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct Volume Growth	Infarct volume at 48 (-12/+24) hours - Infarct volume at baseline	48 (-12/+24) hours after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in modified Rankin Scale distribution	The modified Rankin Scale (mRS) is a 7-point ordinal scale ranging from 0 (no disability) to 6 (death). Higher scores indicate worse outcomes. The distribution of mRS scores (0-6) will be compared between treatment groups.	At 90 days post-randomization.
Difference in modified Rankin Scale of 0-1	The modified Rankin Scale (mRS) is a 7-point ordinal scale ranging from 0 (no disability) to 6 (death). Higher scores indicate worse outcomes. The proportion of mRS 0-1 will be compared between treatment groups.	At 90 days post-randomization.
Difference in modified Rankin Scale of 0-2	The modified Rankin Scale (mRS) is a 7-point ordinal scale ranging from 0 (no disability) to 6 (death). Higher scores indicate worse outcomes. The proportion of mRS 0-2 will be compared between treatment groups.	At 90 days post-randomization.
Longitudinal Change of NIHSS Scores	The National Institutes of Health Stroke Scale (NIHSS) is a 42-point ordinal scale ranging from 0 (no stroke symptoms) to 42 (severe stroke). Higher scores indicate worse neurological deficits. NIHSS scores will be serially assessed at specified intervals.	At 24 hours, 3 days, and 5-7 days post-randomization or at discharge.
Final infarct volume	Infarct volume at 48 (-12/+24) hours post-randomization.	48 (-12/+24) hours after randomization
Immediate postprocedural infarct volume	Infarct volume measured within 2 hours after procedure.	Within 2 hours after procedure.
Occurrence of early neurological improvement	The National Institutes of Health Stroke Scale (NIHSS) is a 42-point ordinal scale ranging from 0 (no stroke symptoms) to 42 (severe stroke). Higher scores indicate worse neurological deficits. Early neurological improvement is defined as a reduction in NIHSS score by ≥8 points.	Within 24 hours post-randomization.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood brain barrier permeability as measured by K-trans value using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)	Ktrans reflects the rate at which contrast agent passes from the intravascular space into the brain tissue and serves as an indicator of BBB disruption. Higher Ktrans values indicate greater BBB permeability and more severe BBB injury.	At 48 (-12/+24) hours post-randomization.
Multi-omics analysis of protein and metabolite quantitative changes using mass spectrometry-based proteomics and metabolomics	Protein and metabolite abundances will be normalized and compared between study groups to identify differentially expressed molecules and biological pathways associated with treatment response.	Within 6 hours after randomization
Percentage of platelet-neutrophil aggregates (CD41+CD66b+ cells) measured by flow cytometry	Higher percentages indicate increased platelet-neutrophil interactions and enhanced thrombo-inflammatory activity.	Within 30 minutes after the procedure.
Percentage of activated platelets (CD41+CD62+ cells) measured by flow cytometry	Higher percentages indicate increased platelet activation and prothrombotic potential.	Within 30 minutes after the procedure.
Percentage of activated neutrophils (CD11b+ cells) measured by flow cytometry	Higher percentages indicate greater neutrophil activation and inflammatory response.	Within 30 minutes after the procedure.
R time (reaction time) measured by thromboelastogram (TEG)	Quantitative assessment of clot initiation dynamics using TEG. R time measures the latency to initial fibrin formation (reported in seconds). Lower values indicate faster clot initiation, while higher values suggest delayed clotting.	Within 30 minutes after the procedure.
K time (clot kinetics) measured by thromboelastogram (TEG)	Quantitative assessment of clot formation speed using TEG. K time reflects the time from clot initiation to a fixed clot strength (reported in seconds). Lower values indicate faster clot kinetics, while higher values suggest slower clot formation.	Within 30 minutes after the procedure.
Alpha angle measured by thromboelastogram (TEG)	Quantitative assessment of fibrin polymerization rate using TEG. The alpha angle (reported in degrees) represents the slope of clot strengthening. Higher values indicate faster fibrin cross-linking and clot stability.	Within 30 minutes after the procedure.
MA (maximum amplitude) measured by thromboelastogram (TEG)	Quantitative assessment of clot strength using TEG. MA (reported in millimeters) measures the maximum clot firmness. Higher values indicate stronger clot structure, while lower values suggest weaker clot integrity.	Within 30 minutes after the procedure.
EPL (estimated percent lysis) measured by thromboelastogram (TEG)	Quantitative assessment of clot lysis potential using TEG. EPL (reported as a percentage) estimates the percentage of clot lysed after maximum amplitude is reached. Higher values indicate greater fibrinolysis activity.	Within 30 minutes after the procedure.
LY30 (lysis at 30 minutes) measured by thromboelastogram (TEG)	Quantitative assessment of late-stage clot lysis using TEG. LY30 measures the percentage of clot lysed 30 minutes after maximum amplitude. Higher values indicate increased fibrinolysis over time.	Within 30 minutes after the procedure.

Collaborators and Investigators

• Sponsor: Tianjin Huanhu Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2024
• Primary Completion (Actual): August 15, 2025
• Study Completion (Actual): August 15, 2025

Study Registration Dates

• First Submitted: August 1, 2024
• First Submitted That Met QC Criteria: August 8, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 10, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Stroke, Acute; Large Vessel Occlusion; Neuroprotection
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: TJHH-2024-WM28

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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