Ischemic Post-conditioning in Acute Ischemic Stroke Thrombectomy (PROTECT-2)

Efficacy and Safety of Ischemic Post-conditioning in Patients with Acute Ischemic Stroke After Mechanical Thrombectomy

Ischemic post-conditioning is a neuroprotective strategy that has been proven to attenuate reperfusion injury in animal models of stroke. The investigators have conducted a 3 + 3 dose-escalation trial to demonstrate the safety and tolerability of ischemic post-conditioning incrementally for a longer duration of up to 5 min × 4 cycles in stroke patients undergoing mechanical thrombectomy. The purpose of this study is to further determine the efficacy and safety of ischemic post-conditioning in patients with acute ischemic stroke who are treated with mechanical thrombectomy.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Procedure: Mechanical thrombectomy alone; Procedure: Mechanical thrombectomy combined with ischemic post-conditioning

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xunming Ji, MD; Phone Number: 010-83198952; Email: jixm@ccmu.edu.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300350
      • Recruiting
      • Tianjin Huanhu Hospital
      • Contact: Ming We, MD; Phone Number: +86-13502182903; Email: drweiming@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years;
2. Acute ischemic stroke within 24 hours from stroke onset (or from time last known well) to groin puncture;
3. Previous mRS ≤ 2;
4. Baseline NIHSS ≥ 6;
5. Baseline ASPECTS ≥ 6;
6. Unilateral middle cerebral artery occlusion with or without ipsilateral internal carotid artery occlusion;
7. Successful recanalization after mechanical thrombectomy (eTICI 2b-3);
8. Written informed consent provided by the patients or their legal relatives.

Exclusion Criteria:

1. Confirmed or clinically suspected cerebral vasculitis/fibromuscular dysplasia;
2. Difficulty in reaching the designated position of the balloon used for ischemic post-conditioning;
3. Complications related to thrombectomy, such as contrast agent extravasation, vascular perforation/rupture, dissection, and escape of thrombus;
4. Stenting in the middle cerebral artery M1 segment/distal intracranial carotid artery during thrombectomy;
5. > 2 times of balloon dilations as rescue therapy due to angioplasty during thrombectomy;
6. Patients with contraindications to MRI;
7. Other conditions that the investigator considered inappropriate for inclusion.

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
Experimental: Ischemic post-conditioning group; Mechanical thrombectomy combined with ischemic post-conditioning	Procedure: Mechanical thrombectomy combined with ischemic post-conditioning; Ischemic post-conditioning will be applied after successful recanalization of the culprit artery achieve by thrombectomy. Ischemic post-conditioning consists of briefly repeated 4 cycles × 2 minutes of occlusion and reperfusion (equal duration) of the initially occluded artery using a balloon.
Sham Comparator: Control group; Mechanical thrombectomy alone	Procedure: Mechanical thrombectomy alone; Successful recanalization was achieved by mechanical thrombectomy without subsequent ischemic post-conditioning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct volume at 24 hours	Infarct volume on MRI-DWI at 24 hours after randomization	24 hours after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression of infarct volume between baseline and 24 hours	Difference of infarct volume on MRI-DWI between baseline and 24 hours after randomization	Baseline and 24 hours after randomization
Progression of perfusion defect from baseline to 24 hours	The volume difference of Tmax > 6 s from baseline to 24 hours after randomization	Baseline and 24 hours after randomization
Progression of infarct volume between 2 hours and 24 hours	Difference of infarct volume on MRI-DWI between 2 h after randomization and 24 h after randomization	2 hours after randomization and 24 hours after randomization
Infarct volume at 5 days/at discharge	Infarct volume on CT/MRI-FLAIR at 5 days after randomization/at discharge	5 days after randomization or at discharge
The proportion of functional independence at 90 days	The modified Rankin Scale (mRS) score of 0-2 at 90 days after randomization; the mRS is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability, and 6=death)	90 days after randomization
The proportion of favorable outcome at 90 days	The mRS score of 0-3 at 90 days after randomization; the mRS is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability, and 6=death)	90 days after randomization
The distribution of mRS score at 90 days	The distribution of the mRS score at 90 days after randomization; the mRS is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability, and 6=death)	90 days after randomization
National Institute of Health Stroke Scale (NIHSS) score at 24 hours	NIHSS score at 24 hours after randomization; the NIHSS ranges from 0 to 42, with higher scores indicating more severe neurologic deficits	24 hours after randomization
The proportion of early neurological improvement	NIHSS 0-2 or ≥ 8 lower than baseline NIHSS score at 24 hours after randomization; the NIHSS ranges from 0 to 42, with higher scores indicating more severe neurologic deficits	Baseline and 24 hours after randomization
National Institute of Health Stroke Scale (NIHSS) score at 5 days/at discharge	NIHSS score at 5 days after randomization/at discharge; the NIHSS ranges from 0 to 42, with higher scores indicating more severe neurologic deficits	5 days after randomization or at discharge
Recanalization rate at 24 hours	Recanalization rate at 24 hours after randomization (eTICI 2b-3)	24 hours after randomization
Cerebral blood flow velocity of the culprit middle cerebral artery at 24 hours after randomization.	Cerebral blood flow will be assessed by transcranial Doppler ultrasound at 24 hours after randomization	24 hours after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedure-related complications	Vascular perforation/rupture, vessel dissection, severe vasospasm, rupture of the balloon used for post-conditioning	During the procedure
Safety outcome (mortality at 90 days)	90-day mortality	90 days after randomization
Safety outcome (the proportion of symptomatic intracranial hemorrhage within 24 hours)	The proportion of symptomatic intracranial hemorrhage within 24 hours after randomization	Within 24 hours after randomization
Safety outcome (the proportion of intracranial hemorrhage within 24 hours)	The proportion of intracranial hemorrhage within 24 hours after randomization	Within 24 hours after randomization
Safety outcome (the proportion of malignant brain edema within 24 hours)	The proportion of malignant brain edema within 24 hours after randomization	Within 24 hours after randomization

Collaborators and Investigators

• Sponsor: Capital Medical University

Publications and helpful links

General Publications

• Wu L, Zhang B, Zhao W, Ji X, Wei M. Ischemic post-conditioning in acute ischemic stroke thrombectomy: A phase-I duration escalation study. Front Neurosci. 2022 Dec 8;16:1054823. doi: 10.3389/fnins.2022.1054823. eCollection 2022.
• Wu L, Wei M, Zhang B, Zhang B, Chen J, Wang S, Luo L, Liu S, Li S, Ren C, Hess DC, Song H, Zhao W, Ji X. Safety and Tolerability of Direct Ischemic Postconditioning Following Thrombectomy for Acute Ischemic Stroke. Stroke. 2023 Sep;54(9):2442-2445. doi: 10.1161/STROKEAHA.123.044060. Epub 2023 Jul 27.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: March 16, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 21, 2025
• Last Verified: March 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; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Ischemic Stroke; Stroke; Cerebral Infarction; Ischemia
• Other Study ID Numbers: PROTECT-2

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
• product manufactured in and exported from the U.S.: No