Ischemic Post-conditioning in Acute Ischemic Stroke Thrombectomy (PROTECT-1b) (PROTECT)

Effect of Ischemic Post-conditioning on Infarct Volume in Patients With Acute Ischemic Stroke After Mechanical Thrombectomy

Ischemic post-conditioning is a neuroprotective strategy attenuating reperfusion injury in animal stroke models. 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. This study aims to assess the infarct volume after ischemic post-conditioning in patients with acute ischemic stroke who are treated with mechanical thrombectomy.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xunming Ji, MD; Phone Number: +86-10-83198952; Email: jixm@ccmu.edu.cn
• Study Contact Backup: Name: Wenbo Zhao, M.D.; Phone Number: 861083199086; Email: zhaowb@xwh.ccmu.edu.cn

Study Locations

• China
  • Tianjin, China, 300350
    • Recruiting
    • Tianjin Huanhu Hospital
    • Contact: Ming Wei, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years;
• Acute ischemic stroke within 24 hours from stroke onset (or from time last known well) to groin puncture;
• Previous mRS ≤ 2;
• Baseline NIHSS ≥ 6;
• Baseline ASPECTS ≥ 6;
• With an occlusion of unilateral middle cerebral artery M1 segment/distal intracranial carotid artery;
• Successful recanalization (mTICI ≥ 2b) after thrombectomy confirmed by DSA;
• Written informed consent provided by the patients or their legal relatives.

Exclusion Criteria:

• Confirmed or clinically suspected cerebral vasculitis/fibromuscular dysplasia;
• Difficulty in reaching the designated position of the balloon used for ischemic post-conditioning;
• Stenting in the middle cerebral artery M1 segment/distal intracranial carotid artery during thrombectomy;
• > 2 times balloon dilations as rescue therapy due to angioplasty during thrombectomy;
• Moderate/severe residual stenosis (≥ 50%) in the offending artery after thrombectomy;
• Patients with contraindications to MRI;
• Other conditions that the investigator considered inappropriate for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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 by thrombectomy. Ischemic post-conditioning consists of briefly repeated four cycles × 2 minutes of occlusion and reperfusion (equal duration) of the initially occluded artery using a balloon.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct volume	Infarct volume at 72 hours after procedure	72 hours after procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The progression of infarct volume	Difference of infarct volume between baseline and 72 hours after procedure	Baseline and 72 hours after procedure
National Institute of Health Stroke Scale (NIHSS) score	NIHSS score at 24 hours after procedure; the NIHSS ranges from 0 to 42, with higher scores indicating more severe neurologic deficits	24 hours after procedure
The proportion of early neurological improvement	NIHSS 0-2 or ≥8 lower than baseline NIHSS score at 24 hours after procedure; the NIHSS ranges from 0 to 42, with higher scores indicating more severe neurologic deficits	24 hours after procedure
NIHSS score at 7 days after procedure/discharge	NIHSS score at 7 days after procedure/discharge; the NIHSS ranges from 0 to 42, with higher scores indicating more severe neurologic deficits	7 days after procedure/discharge
Recanalization rate	Recanalization rate at 24 hours after procedure (mTICI ≥2b)	24 hours after procedure
The proportion of functional independence at 90 days	The modified Rankin Scale (mRS) score of 0-2 at 90 days after procedure; the mRS is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability, and 6=death)	90 days after procedure
The proportion of favorable outcome at 90 days	The mRS score of 0-3 at 90 days after procedure; the mRS is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability, and 6=death)	90 days after procedure
The distribution of the mRS score at 90 days	The distribution of the mRS score at 90 days after procedure; the mRS is an ordinal disability score of 7 categories (0=no symptoms to 5=severe disability, and 6=death)	90 days after procedure
Hemodynamic assessment	Hemodynamic assessment within 24 hours after procedure	Within 24 hours after procedure

Other Outcome Measures

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

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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): March 31, 2024

Study Registration Dates

• First Submitted: June 9, 2023
• First Submitted That Met QC Criteria: June 9, 2023
• First Posted (Estimated): June 19, 2023

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

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; Postoperative Complications; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Reperfusion Injury
• Other Study ID Numbers: PROTECT-1b

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