Clinical trial NCT06940128: Direct Ischemic Conditioning for Endovascular Recanalization for Anterior Large Vessel Occlusion (DICER-aLVO)
Official title: Direct Ischemic Conditioning for Endovascular Recanalization for Anterior Large Vessel Occlusion (DICER-aLVO): a Prospective, Randomized, Open Label, Blinded-end Point, Phase 2, Multi-centre Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ischemic Stroke
Keywords: Direct Ischemic Conditioning
stroke
Endovascular Recanalization
Lead sponsor: General Hospital of Shenyang Military Region
Sponsor class: OTHER
First posted: 2025-04-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Acute ischemic stroke (AIS) is the most common type of stroke, with high incidence rate and mortality. Endovascular therapy is currently the most effective treatment for AIS with large vessel occlusion, but only about 50% of patients achieve good outcome after endovascular therapy, while 50% of patients have poor prognosis, commonly referred to as ineffective perfusion. Therefore, how to improve ineffective perfusion is currently a hot topic.

Numerous studies have shown that Remote Ischemic Therapy (RIC) has a protective effect on ischemic stroke. Our recent RICAMIS study has demonstrated that RIC can significantly improve the functional prognosis of moderate acute ischemic stroke. Furthermore, direct ischemic conditioning has also showed neuroprotective effect. For example, in a rat model, within 2 minutes after reperfusion, using three cycles of 30 s reperfusion and 10 s occlusion for direct ischemic conditioning can effectively alleviate hyperperfusion and reduce cerebral infarction volume. Meanwhile, in previous clinical exploration studies, it was found that even induction by 5-minute ischemia and 5-minute reperfusion for up to 4 cycles is safe, feasible, and well tolerated for AIS patients receiving endovascular treatment. Immediate control of bilateral carotid artery blood flow after ischemia-reperfusion can significantly reduce cerebral infarction area and brain edema, and improve neurological function recovery in rats. Subsequent molecular mechanism studies have shown that direct ischemic conditioning can reduce the production of free radicals after cerebral ischemia-reperfusion, inhibit inflammatory reactions and cell apoptosis, downregulate the expression of signaling molecules mediating brain edema, promote Akt survival pathway, and improve the integrity of the blood-brain barrier, thereby exerting neuroprotective effects. Recent studies have also confirmed the safety and feasibility of direct ischemic conditioning for stroke patients achieving successful recanalization. More importantly, a recent cohort study has shown that direct ischemic conditioning can reduce infarct growth and brain edema after reperfusion in patients with AIS who have undergone thrombectomy for occlusion of large blood vessels in the anterior circulation, and improve prognosis after 90 days.

Based on the above discussion, this trial aims to evaluate the effectiveness and safety of direct ischemic conditioning for patients with AIS who have undergone thrombectomy for occlusion of large blood vessels in the anterior circulation.


Eligibility criteria: Inclusion Criteria:

-1. Over 18 years old; 2. The time from onset to randomization is less than 24 hours; 3. Patients with acute anterior artery occlusion and receiving successful recanalization (mTICI 2b-3) after endovascular treatment and with residual stenosis ≤ 50%; 4. Cerebral circulation time after successful recanalization: affected side ≤ healthy side; 5. PH2 hemorrhage was excluded by immediate postoperative CT examination; 6. Re-onset patients with first onset or past onset without sequelae such as limb paralysis should not affect the score of this NIHSS, and mRS Score of patients with past onset should be less than 2 points; 7. Signed informed consent by patient or their legally authorized representative.

Exclusion Criteria:

- 1. Spherical enlargement of the lesion site twice or more; 2. Proximal residual stenosis \>50% for patients with tandem lesions; 3. Intracranial hemorrhagic diseases: cerebral hemorrhage, subarachnoid hemorrhage, etc.

4. Chronic liver disease, liver and kidney insufficiency, elevated ALT or AST (greater than 2 times the upper limit of normal), elevated serum creatinine (greater than 1.5 times the upper limit of normal) or dependent on kidney dialysis; 5. Women who are pregnant, have a pregnancy plan or are breastfeeding; 6. Combined with serious other diseases, life expectancy \< 6 months; 7. Other conditions deemed inappropriate for participation in this study.

Primary outcomes:
measure: Proportion of patients with modified Rankin Score (mRS) 0 to 2
timeFrame: at 90±7 days
Secondary outcomes:
measure: distribution of modified Rankin Score (mRS)
timeFrame: at 90±7 days
measure: Proportion of patients with modified Rankin Score (mRS) 0 to 1
timeFrame: at 90±7 days
measure: Proportion of early neurological improvement
timeFrame: at 24 (-6/+24) hours
measure: Change in National Institute of Health stroke scale (NIHSS) score
timeFrame: at 24 (-6/+24) hours
measure: Change in National Institute of Health stroke scale (NIHSS) score
timeFrame: at 10±2 days
measure: The amount of contrast exudation after treatment (CT assessment)
timeFrame: at 24 (-6/+24) hours
measure: The amount of midline shift of the brain on neuroimaging after treatmet
timeFrame: at 24 (-6/+24) hours
measure: Changes in brain circulation time after treatment (between healthy side and affected side, before and after treatment of affected side ischemia)
timeFrame: immediately after treatment
measure: Recurrent stroke and new cardiovascular and cerebrovascular events
timeFrame: at 90±7 days
measure: Proportion of balloon treatment-related complications (responsible vessel re-occlusion, vagal reflex, dissection, plaque shedding, and vasospasm during and after treatment)
timeFrame: immediately after treatment
measure: Proportion of symptomatic intracranial hemorrhage
timeFrame: at 24 (-6/+24) hours
measure: Proportion of occurrence of cerebral parenchymal hemorrhage types (PH1) and (PH2)
timeFrame: at 24 (-6/+24) hours
measure: Proportion of serious adverse events
timeFrame: at 24 (-6/+24) hours
measure: Proportion of all-cause deaths
timeFrame: at 10 days
Other outcomes:
measure: Changes in serum biomarkers
timeFrame: at 24 (-6/+24) hours
measure: Changes in cerebral blood flow autoregulation ability
timeFrame: at 24 (-6/+24) hours
Locations:
city: Shengyang
country: China
facility: General Hospital of Northern Theater Command
state: Liaoning
Study officials:
References: