Clinical trial NCT06307743: Rapid Local Ischemic Postconditioning in Acute Ischemic Stroke
Official title: A Multicenter, Open Label, Blind Endpoint, Clinical Trial to Evaluate the Efficacy and Safety of Rapid Local Ischemic Postconditioning in Acute Ischemic Stroke Patients Received Successful Thrombectomy Reperfusion
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Acute Ischemic Stroke
Mechanical Thrombectomy
Ischemic Postconditioning
Brain Edema
Lead sponsor: Shanghai Jiao Tong University Affiliated Sixth People's Hospital
Sponsor class: OTHER
Collaborators: name: Zhangzhou Municipal Hospital of Fujian Province
name: Shanghai East Hospital
name: First People's Hospital of Hangzhou
name: RenJi Hospital
First posted: 2024-03-13
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years old
2. Presenting with symptoms consistent with acute ischemic stroke
3. Pre-stroke mRS score 0-1
4. Baseline NIHSS score≥6
5. Endovascular treatment can be initiated (femoral puncture) within 24 hours from stroke onset (stroke onset time is defined as last known well time)
6. 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
7. 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.
8. Embolism verified as the etiology of occluded artery and mTICI 2b or 3 regained after mechanical thrombectomy
9. Informed consent signed

Exclusion Criteria:

1. Stenosis of the proximal middle cerebral artery, internal carotid artery, or common carotid artery (≥50%) of the culprit artery
2. Multiple vascular embolism on different pathways (not refers to the ipsilateral middle artery and anterior artery)
3. Pre ischemic stroke or transient ischemic attack within past 3 months
4. The expected survival time is less than 6 months, could not be followed at 90 days (such as patient with malignant tumor)
5. Currently pregnant, mental disease, advanced hepatic and renal insufficiency, severe heart failure
6. Participation in other interventional randomized clinical trials that may confound the outcome assessment of the trial
7. Other circumstances that the investigator considers inappropriate for this trial

Primary outcomes:
measure: Number of Participants without clinically meaningful cerebral swelling, significant increase in infarct volume from baseline and intervention-related serious adverse events.
timeFrame: 24 hours after procedure
Secondary outcomes:
measure: Rate of participants without clinically meaningful cerebral swelling
timeFrame: 24 hours after procedure
measure: Rate of participants with significant increase in infarct volume from baseline or intervention-related serious adverse events.
timeFrame: 24 hours after procedure
measure: Change in volume of cerebrospinal fluid (∆CSF72) at 72 hours
timeFrame: 72 hours after procedure
measure: Change of net water uptake (∆NWU24) at 24 hours
timeFrame: 24 hours after procedure
measure: Change of net water uptake (∆NWU72) at 72 hours
timeFrame: 72 hours after procedure
measure: Midline shift at 24 hours
timeFrame: 24 hours after procedure
measure: Midline shift at 72 hours
timeFrame: 72 hours after procedure
measure: Change of NIHSS at 24 hours
timeFrame: 24 hours after procedure
measure: Early therapeutic response to treatment
timeFrame: 24 hours after procedure
measure: Good outcome at 90 days
timeFrame: 90 days after procedure
measure: Excellent outcome at 90 days
timeFrame: 90 days after procedure
Other outcomes:
Locations:
Study officials:
affiliation: Shanghai Jiao Tong University Affiliated Sixth People's Hospital
name: Yueqi Zhu, MD
role: PRINCIPAL_INVESTIGATOR
References: