Rapid Local Ischemic Postconditioning in Acute Ischemic Stroke
- Conditions
- Acute Ischemic StrokeIschemic PostconditioningMechanical ThrombectomyBrain Edema
- Interventions
- Procedure: rapid local ischemic postconditioning
- Registration Number
- NCT06307743
- Lead Sponsor
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital
- Brief Summary
The objective of this clinical trial is to determine whether rapid local ischemic postconditioning (RL-IPostC) is effective in preventing brain edema and safe in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy. In this trial, researchers will block antegrade cerebral blood flow temporarily by the way of balloon 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. Researchers will evaluate the protective role and safety of different duration of balloon inflation/deflation. The optimal postconditioning intervention dose will be determined for further confirmative investigation.
- Detailed Description
This will be an umbrella trial of testing the efficacy and safety of three postconditioning intervention doses. It will be a prospective, open-label, blinded endpoint, three-dose Bayesian Optimal Phase 2(BOP2) design trial with interim efficacy and safety monitoring. The maximum number of subjects for this trial is estimated as 135 patients. Eligible patients are 18 years or older with symptomatic large vessel occluded (LVO) AIS treated with mechanical thrombectomy (MT) achieving successful reperfusion defined as mTICI score 2b or 3. Patients will receive 5 cycles of balloon inflation/deflation at ipsilateral C1 segment of internal carotid artery (ICA) for the temporary occlusion of the restoration of antegrade blood flow. Three postconditioning intervention doses of 30s/30s, 60s/60s and 180s/180s were adopted for block and restore of blood blow. The primary outcome is a favorable binary outcome defined as no clinically meaningful brain swelling from baseline to 24 hours and no clinically meaningful infarction growth from baseline to 24 hours and no causally attributable serious adverse events (SAEs). It's a composite outcome of efficacy and safety outcome. Key secondary outcomes include efficacy outcome indicating no clinically meaningful brain swelling defined by cerebral spinal fluid (CSF) volume reduction≤5 mL from baseline to 24 hours and safety outcome indicating infarct volume growth\>10 mL from baseline to 24 hours or causally attributable SAEs. Other secondary outcomes include change of brain net water uptake, midline shift and functional outcome. For each intervention dose, we will perform the interim analyses following pre-defined optimized Bayesian rule for early stopping to make a go/no-go decision when the number of enrolled patients reaches 10, 20, 30. The optimal intervention dose will be determined according to the number of patients reach the primary endpoints in different groups.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 135
- Age ≥ 18 years old
- Presenting with symptoms consistent with acute ischemic stroke
- Pre-stroke mRS score 0-1
- Baseline 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(M1 or M2) confirmed by CTA or MRA, and is the culprit artery
- Alberta Stroke Program Early CT Score (ASPECTS) (based on non-contrast CT) >5 on noncontrast computed tomography (NCCT) for stroke onset time less than 6 hours, infarct Core < 70 ml (defined as rCBF <30% on CT perfusion) and mismatch ratio > 1.2 (penumbra defined as Tmax >6 seconds volume) for stroke onset time between 6 and 24 hours.
- Embolism verified as the etiology of occluded artery and mTICI 2b or 3 regained after mechanical thrombectomy
- Informed consent signed
- Stenosis of the proximal middle cerebral artery, internal carotid artery, or common carotid artery (≥50%) of the culprit artery
- Multiple vascular embolism on different pathways (not refers to the ipsilateral middle artery and anterior artery)
- Pre ischemic stroke or transient ischemic attack 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 RL-IPostC 30 rapid local ischemic postconditioning The RL-IPostC 30 protocol involved 5 cycles of blow block and restoration, each for 30 seconds. RL-IPostC 60 rapid local ischemic postconditioning The RL-IPostC 60 protocol involved 5 cycles of blow block and restoration, each for 60 seconds. RL-IPostC 180 rapid local ischemic postconditioning The RL-IPostC 180 protocol involved 5 cycles of blow block and restoration, each for 180 seconds.
- Primary Outcome Measures
Name Time Method Number of Participants without clinically meaningful cerebral swelling, significant increase in infarct volume from baseline and intervention-related serious adverse events. 24 hours after procedure No clinically meaningful cerebral swelling defined as volume reduction of cerebrospinal fluid ≤ 5 mL from baseline. No significant increase in infarct volume from baseline defined as an increase in infarct volume of ≤ 10 mL. Intervention-related serious adverse events defined as SAEs specifically related to RL-IPostC other than mechanical thrombectomy.
- Secondary Outcome Measures
Name Time Method Change of net water uptake (∆NWU72) at 72 hours 72 hours after procedure Change of net water uptake (∆NWU72) at 72 hours from baseline
Good outcome at 90 days 90 days after procedure Proportion of mRS score of 0 to 2 at 90 days
Rate of participants with significant increase in infarct volume from baseline or intervention-related serious adverse events. 24 hours after procedure Significant increase in infarct volume from baseline defined as an increase in infarct volume of more than 10 mL. Intervention-related serious adverse events defined as SAEs specifically related to RL-IPostC other than mechanical thrombectomy.
Midline shift at 72 hours 72 hours after procedure Distance of midline shift at 72 hours (in millimeters at the level of the septum pellucidum)
Rate of participants without clinically meaningful cerebral swelling 24 hours after procedure No clinically meaningful brain swelling defined by CSF volume reduction≤5 mL from baseline to 24 hours.
Change in volume of cerebrospinal fluid (∆CSF72) at 72 hours 72 hours after procedure Change in volume of cerebrospinal fluid (∆CSF72) at 72 hours from baseline
Change of net water uptake (∆NWU24) at 24 hours 24 hours after procedure Change of net water uptake (∆NWU24) at 24 hours from baseline
Change of NIHSS at 24 hours 24 hours after procedure Change of NIHSS at 24 hours from baseline
Early therapeutic response to treatment 24 hours after procedure Decrease in the NIHSS score of ≥8 from baseline or an NIHSS score of 0 to 2 at 24 hours)
Midline shift at 24 hours 24 hours after procedure Distance of midline shift at 24 hours (in millimeters at the level of the septum pellucidum)
Excellent outcome at 90 days 90 days after procedure Proportion of mRS score of 0 to 1 at 90 days