Local Ischemic Postconditioning in Acute Ischemic Stroke

Not Applicable

Recruiting

• Conditions: Brain Edema; Mechanical Thrombectomy; Ischemic Postconditioning; Neuroprotection; Acute Ischemic Stroke
• Interventions: Procedure: rapid local ischemic postconditioning

• Registration Number: NCT06526429
• Lead Sponsor: Shanghai Jiao Tong University Affiliated Sixth People's Hospital

Brief Summary

This study aims to determine the safety and optimal dose of rapid local ischemic postconditioning in acute ischemic stroke(AIS) patients received successful thrombectomy reperfusion. In this trial, investigators will halt antegrade cerebral blood flow temporarily by the way of balloon guiding catheter (BGC) 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. The optimal postconditioning intervention dose will be determined for further investigation.

Detailed Description

This will be an Bayesian Optimal Interval Phase I/II (BOIN12) trial design to determine the safety and optimal dose of ischemic postconditioning intervention. The BOIN12 design makes the decision of dose escalation and de-escalation by simultaneously taking account of toxicity and efficacy and it quantifies the desirability of a dose in terms of toxicity-efficacy trade off. Under BOIN12, patients are adaptively assigned to the most desirable dose with the optimal toxicity-efficacy trade-off.

Eligible patients are 18 years or older with symptomatic large vessel occluded (LVO) AIS treated with mechanical thrombectomy (MT) achieving successful reperfusion defined as modified thrombolysis in cerebral infarction (mTICI) score 2b or 3. Participants will receive balloon inflation/deflation at ipsilateral C1 segment of internal carotid artery (ICA) for the temporary occlusion of the antegrade blood flow.

Six postconditioning intervention doses were adopted for blocking and restoration of blood blow. This study will include 6 doses with the start dose set at dose 180. Dose 15: 15s/15s, 5 cycles; Dose 60: 60s/60s, 4 cycles; Dose 120: 120s/120s, 4 cycles; Dose 180: 180s/180s, 4 cycles; Dose 240: 240s/240s, 4 cycles; Dose 300: 300s/300s, 4 cycles. In this trial, a maximum number of 60 participants will be enrolled with a cohort size of 5 and cohort number of 12. The maximum sample size of each dose is set at 20.

The safety outcome within 7 days (dose limiting toxicity, DLT) including any one of: 1) malignant middle cerebral artery (MCA) infarction defined as midline shift ≥5 mm at the level of septum pellucidum, or anisocoria attributable to herniation, or death attributable to herniation; 2) procedure related serious adverse events(SAEs); 3) other causally attributable SAEs. Efficacy outcome was patients without clinically meaningful infarction growth at 72 hours (defined as infarction growth\<10 mL from baseline to 72 hours).

Study Timeline

• Study First Submitted: 2024-07-24
• Study First Submitted QC: 2024-07-27
• Study First Posted: 2024-07-29
• Status Verified: 2024-10
• Study Start: 2024-10-14
• Last Update Submitted: 2024-10-14
• Last Update Posted: 2024-10-16
• Primary Completion: 2026-01-31
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Age ≥ 18 years old
• Presenting with symptoms and signs consistent with acute anterior circulation ischemic stroke
• Pre-stroke modified Rankin Score 0-1
• Baseline National Institute of Health Stroke Scale (NIHSS) score≥6
• Endovascular treatment can be initiated (femoral puncture) within 24 hours from stroke onset (stroke onset time is defined as last known well time)
• Occlusion of the intracranial internal carotid artery, or the middle cerebral artery (MCA) (M1 or M2) and is the culprit artery
• Ischemic core volume is < 70 ml, mismatch ratio is >1.8 and mismatch volume is >15 ml as determined by CT perfusion imaging
• Embolism verified as the etiology of occluded artery and modified Thrombolysis in Cerebral Infarction Score (mTICI) 2b or 3 achieved after mechanical thrombectomy.
• Time from CT perfusion to reperfusion < 2 hours
• Informed consent signed

Exclusion Criteria

• Stenosis of the proximal middle cerebral artery, internal carotid artery, or common carotid artery (≥50%) of the culprit artery
• Evidence of internal carotid artery lesion that precludes the access and application of balloon guide catheter
• Multiple vascular embolism on different pathways (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion)
• Pre ischemic stroke within past 3 months
• The expected survival time is less than 6 months, could not be followed at 90 days (such as patient with malignant tumor)
• Currently pregnant, mental disease, advanced hepatic and renal insufficiency, severe heart failure
• Participation in other interventional randomized clinical trials that may confound the outcome assessment of the trial
• Other circumstances that the investigator considers inappropriate for this trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose 120	rapid local ischemic postconditioning	Dose 120 involved 4 cycles of blow block and restoration, each for 120 seconds.
Dose 180	rapid local ischemic postconditioning	Dose 180 involved 4 cycles of blow block and restoration, each for 180 seconds.
Dose 15	rapid local ischemic postconditioning	Dose 15 involved 5 cycles of blow block and restoration, each for15 seconds.
Dose 300	rapid local ischemic postconditioning	Dose 300 involved 4 cycles of blow block and restoration, each for 300 seconds.
Dose 60	rapid local ischemic postconditioning	Dose 60 involved 4 cycles of blow block and restoration, each for 60 seconds.
Dose 240	rapid local ischemic postconditioning	Dose 240 involved 4 cycles of blow block and restoration, each for 240 seconds.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	within 7 days	Treatment-Emergent Adverse Events including any one of below: 1. Malignant middle cerebral artery infarction defined as midline shift ≥5 mm at the level of septum pellucidum, or anisocoria attributable to herniation, or death attributable to herniation.; 2. Complications related to ischemic postcondition intervention that require treatment including distal vascular embolism, local arterial dissection, and local vascular spasm at the intervention site of the internal carotid artery.; 3. Other causally attributable serious adverse events (SAEs)

Trial Locations

Locations (1)

Shanghai Jiao Tong University Affiliated Sixth People's Hospital; 🇨🇳 Shanghai, China