Ischemic Post-conditioning in the Treatment of Acute Ischemic Stroke

Acute Ischemic Stroke Clinical Trial

Official title:

Ischemic Post-conditioning in the Treatment of Acute Ischemic Stroke--a Multicenter, Prospective Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06456437
• Other study ID #: TJHH-2023-WM26
• Status: Recruiting
• Start date: November 1, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2024
• Source: Tianjin Huanhu Hospital
• Contact: Ming Wei, PhD
• Phone: 13502182903
• Email: drweiming[@]163.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Post-ischemic adaptation is a physical brain protective treatment strategy in which an ischemic event in an organ or tissue is treated and blood flow is restored, and an ischemic stimulus is given to local tissues to induce the production of anti-ischemic damage factors and reduce the damage associated with reperfusion therapy . Relevant basic studies have confirmed that post-ischemic adaptation can reduce infarct volume and promote neurological function recovery in animal models of cerebral infarction. Therefore, it may be beneficial to the recovery of neurological function in patients with acute ischemic stroke undergoing mechanical thrombus extraction.

Based on the above background, the use of a balloon to repeatedly dilate-contract at the original occlusion site after revascularization to block and restore arterial flow may be an effective cerebroprotective treatment for patients with large-vessel occlusion who undergo thrombolysis. However, can this approach be safely used in patients with acute ischemic stroke treated with thrombolysis? What is the protocol for the length of time patients can tolerate post-ischemic adaptation? The application of this method in the treatment of acute ischemic stroke will be explored in this study.

Description:

Stroke has become the second leading cause of death in the world and the first cause of death and disability in adults in China; among them, ischemic stroke (AIS) accounts for about 80% of all strokes, and is the most important type of stroke . Ischemic stroke is usually caused by acute occlusion of cerebral blood vessels, therefore, opening the occluded blood vessels is the key to its treatment; at present, intravenous thrombolysis and endovascular mechanical thrombolysis are recommended by domestic and international guidelines for recanalization of blood vessels, and they have become the most effective treatment measures for ischemic stroke . However, due to the short therapeutic time window (<4.5 hours) and low recanalization rate of large vessel occlusion (less than 20%) of intravenous thrombolysis, endovascular mechanical thrombolysis is increasingly favored because of its long therapeutic time window, high recanalization rate of large vessel occlusion, and other advantages . However, although mechanical thrombolysis has a high rate of revascularization, the clinical prognosis of patients is not satisfactory, and both domestic and international studies have found that among patients treated with mechanical thrombolysis, the percentage of disability-free at 3 months is less than 30%, while the rate of death and disability is as high as more than 70% . The ischemia-reperfusion injury that occurs after revascularization may be the root cause of patients' still unsatisfactory prognosis . Therefore, trying to reduce ischemia-reperfusion injury after opening the occluded vessel to further improve the prognosis of patients is a scientific problem that needs to be solved urgently nowadays.

At present, scholars at home and abroad agree that effective neuroprotective therapy based on revascularization is expected to be an important treatment method to further improve the prognosis of patients with AIS, but there is no conclusion on how revascularization should be combined with neuroprotective therapy ; moreover, although a large number of studies have been carried out on neuroprotective therapy for acute ischemic stroke and hundreds of measures have been confirmed to have neuroprotective effects by animal experiments, the neuroprotective effects of such measures are not yet known. In addition, although a large number of studies have been conducted on neuroprotective therapy for acute ischemic stroke, and hundreds of measures have been demonstrated to be neuroprotective by animal experiments, there are still no clinically available neuroprotective measures .

Post-ischemic adaptation is a physical brain protective treatment strategy in which an ischemic event in an organ or tissue is treated and blood flow is restored, and an ischemic stimulus is given to local tissues to induce the production of anti-ischemic damage factors and reduce the damage associated with reperfusion therapy . This method has been widely studied in the field of coronary heart disease rescue, and the results suggest that in situ ischemic post-adaptation immediately after coronary revascularization can safely and effectively reduce ischemia-reperfusion myocardial injury, reduce the size of myocardial infarction, and improve clinical prognosis . The process of mechanical thrombolysis for acute ischemic stroke is similar to that of emergency recanalization for acute coronary syndromes, and relevant basic studies have confirmed that post-ischemic adaptation can reduce infarct volume and promote neurological function recovery in animal models of cerebral infarction. Therefore, it may be beneficial to the recovery of neurological function in patients with acute ischemic stroke undergoing mechanical thrombus extraction.

Based on the above background, the use of a balloon to repeatedly dilate-contract at the original occlusion site after revascularization to block and restore arterial flow may be an effective cerebroprotective treatment for patients with large-vessel occlusion who undergo thrombolysis. However, can this approach be safely used in patients with acute ischemic stroke treated with thrombolysis? What is the protocol for the length of time patients can tolerate post-ischemic adaptation? The application of this method in the treatment of acute ischemic stroke will be explored in this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2025
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1)Ischemic stroke confirmed by CT or MRI of the head;

• 2) Large vessel occlusion confirmed by CTA or MRA of the head, including: intracranial internal carotid artery (ICA), middle cerebral artery (MCA M1/M2), anterior cerebral artery (ACA A1/A2), basilar artery (BA), vertebral artery (VA), and posterior cerebral artery (PCA P1/P2);

• 3) Recanalization of the occluded vessel at eTICI grade 2b/3 as confirmed by DSA after thrombectomy;

• 4)The patient/legally authorized representative has signed an informed consent form.

Exclusion Criteria:

• 1) Inability to perform an MRI or CT scan for any reason;

• 2)The patient has any condition that would interfere with neurologic assessment or psychiatric disorders;

• 3)Stroke onset with seizures resulted in the inability to obtain an accurate NIHSS baseline;

• 4)Pregnancy

• 5)Other serious, advanced or terminal illness;

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Infarction
• Ischemia
• Ischemic Stroke
• Large Vessel Occlusion
• Stroke

Intervention

Device:
• Post-conditioning Balloon dilation and contraction
The balloon was filled at a pressure of no more than 4 atm at the original occlusion of the vessel to block blood flow for 2 minutes (confirmed by angiography), and then contracted to reperfuse the blood flow for 2 minutes, and the above steps were repeated 4 times to complete the in situ ischaemic post-acclimatisation intervention.

Locations

Country	Name	City	State
China	Tianjin Huanhu Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Ming Wei

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Infarct volume at 24(-6/+12) h postoperatively	Infarct volume at 24(-6/+12) h postoperatively (CT/DWI, preferred DWI)	24 (-6/+12) h postoperatively
Secondary	Change in final cerebral infarct volume relative to baseline at 24 (-2/+12) hours postoperatively on CT/MR	Change in final cerebral infarct volume relative to baseline at 24 (-2/+12) hours postoperatively on CT/MR	24 hours after thrombectomy
Secondary	Postoperative 90 d mRS score (0-2 vs 3-6)	Percentage of mRS scores 0-2 vs 3-6 at 90 d postoperatively	90 days after thrombectomy
Secondary	Postoperative 90 d mRS score (0-3 vs 4-6)	Percentage of mRS scores 0-3 vs 4-6 at 90 d postoperatively	90 days after thrombectomy
Secondary	Distribution of mRS scores at 90 d postoperatively	Distribution of mRS(modified Rankin scale)scores at 90 d postoperatively	90 days after thrombectomy
Secondary	NIHSS score at 24 h postoperatively	NIHSS(National Institute of Health stroke scale) score at 24 h postoperatively	24 hours after thrombectomy
Secondary	Proportion of patients with a good prognosis early after treatment	Decrease in NIHSS score = 8 or NIHSS score of 0-2 in 24 (-2/+12) hours	24 hours after thrombectomy
Secondary	NIHSS score at 7 d postoperatively/discharge	NIHSS(National Institute of Health stroke scale) score at 7 d postoperatively/discharge	7 days after thrombectomy/time of discharge
Secondary	Vascular recanalization	Postoperative revascularisation assessed by CTA/MRA/DSA using Arterial Occlusive Lesion (AOL) grading at 24 (-2/+12) hours postoperatively; Postoperative revascularisation assessed by CTA/MRA/DSA using modified Thrombolysis In Cerebral Infarction(mTICI) grading at 24 (-2/+12) hours postoperatively; Application of bedside TCD for assessment of revascularisation	24 hours after thrombectomy
Secondary	Haemodynamic assessment within 24 h postoperatively (confirmed by CTA, MRA, DSA or TCD)	This was defined as an exploratory outcome: primary measures included CT or MR perfusion, dynamic contrast contrast-enhanced magnetic resonance (DCE MRI) or permeability surface (PS) detection of the blood-brain barrier.	24 hours after thrombectomy