Intracranial Artery Occlusion With Infarction
Conditions
Keywords
standard medical therapy, symptomatic non-acute intracranial artery occlusion, endovascular recanalization
Brief summary
Background The management of patients with symptomatic nonacute intracranial artery occlusion (sNA-ICAO), which is a special subset with high morbidity and a high probability of recurrent serious ischemic events despite standard medical therapy (SMT), has been clinically challenging. Some small-sample clinical studies have also discussed endovascular recanalization for sNA-ICAO; however, there is currently a lack of evidence from multicenter, prospective, large-sample cohort trials. The aim of our present study was to evaluate the technical feasibility and safety of endovascular recanalization for sNA-ICAO. Methods and analysis: Our group is currently undertaking a multisite, nonrandomized cohort, prospective registry study enrolling consecutive patients presenting with sNA-ICAO at 15 centers in China between May 1, 2020, and April 30, 2023. A cohort of patients who received SMT and a cohort of similar patients who received ER plus SMT were constructed and followed up for 2 years. The primary outcome is the composite of stroke/TIA within 2 years following enrollment and stroke/TIA ipsilateral to the target vessel. The secondary efficacy outcome includes the following two parts: 1) the incidence of stroke/TIA ipsilateral to the target vessel within 30 days and 90 days in both groups; 2) the all-cause mortality, mRS score, NIHSS score and cognitive function at 30 days, 90 days, 8 months, 12 months and 24 months for both groups, including the MRI, CTA/MRA, CTP or MRP results in patients with internal carotid artery or middle cerebral artery occlusion as well as CTA in patients with basilar or vertebral artery occlusion at 90 days, 12 months and 24 months. Descriptive statistics and linear/logistic multiple regression models will be generated. Clinical relevance will be measured as relative risk reduction, absolute risk reduction and the number needed to treat. Ethics and dissemination This study protocol was reviewed and approved primarily by Beijing Tiantan Hospital, the Capital Medical University Medical Ethics Committee, and the institutional review boards of all partner sites. The study is being externally monitored, and the results will be published in open-access peer-reviewed scientific journals and presented to academic and policy stakeholders.
Interventions
BIOLOGICALendovascular recanalization
to recanalize the occlusion cerebral artery with intravascular intervention
Sponsors
Feng Gao
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient age ≥ 18 years old and life expectancy of 5 years or more. 2. Symptomatic sNA-ICAO defined as:diagnosed by CTA or MRA and confirmed by angiography; Vascular occlusion time more than 24 hours;TIA or ischemic stroke (confirmed by CT or MRI) related to the LCAO despite SMT \< 90 days prior to enrollment. 3. Modified Rankin scale score 0-2 at the time of informed consent. 4. More than one risk factor for atherosclerosis. 5. For patients with ICA or MCA M1 segment occlusion, ipsilateral hypoperfusion confirmed by CTP or MRI perfusion imaging prior to enrollment and analysis by the RAPID system. 6. For patients with intracranial segment occlusion of the vertebral artery, severe stenosis or occlusion of the contralateral vertebral artery. 7. Among women, no childbearing potential; or if a woman with childbearing potential, a negative pregnancy test result prior to randomization. 8. Agreement of the patient to comply with all protocol-specified follow-up appointments. 9. Signature by a patient of a consent form that has been approved by the local governing institutional review board (IRB)/medical ethics committee (MEC) of the respective clinical site.
Exclusion criteria
1. Intolerance or allergic reaction to a study medication without a suitable management alternative. 2. No atherosclerotic intracranial vasculopathies, such as dissection, moyamoya disease and vasculitis. 3. Concomitant intracranial aneurysms or any bleeding disorder. 4. Life expectancy \<1 year due to other medical conditions. 5. Large infarction core, defined as an ASPECTS \< 6 in anterior circulation and pc-ASPECTS \< 6 points in posterior circulation. 6. For patients with MCA M1 segment occlusion, concomitant ≥50% stenosis of the proximal internal carotid artery or other intracranial arteries. 7. For patients with intracranial segment occlusion of the vertebral artery, continuance of the occluded vertebral artery to the posterior inferior cerebellar artery with no stump. 8. Incomplete clinical and imaging data. 9. Coexistent cardioembolic source (e.g., atrial fibrillation, mitral stenosis, prosthetic valve, MI within six weeks, intracardiac clot, ventricular aneurysm and bacterial endocarditis). 10. Occlusive lesions with severe calcification. 11. Platelet count \<100,000/ml or history of heparin-induced thrombocytopenia. 12. Left ventricular ejection fraction \<30% or admission for heart failure in the prior 6 months. 13. Extreme morbid obesity that would compromise patient safety during the procedure or the periprocedural period. 14. Coronary artery disease with two or more proximal or major diseased coronary arteries with 70% stenosis that have not or cannot be revascularized. 15. Anticoagulation with Marcumar, warfarin or direct thrombin inhibitors or anti-XA drugs. 16. Chronic atrial fibrillation. 17. Any history of atrial fibrillation or paroxysmal atrial fibrillation in the past 6 months that is considered to require long-term anticoagulant therapy. 18. Other high-risk cardiogenic embolisms, including left ventricular aneurysm, severe cardiomyopathy, aortic or mitral mechanical heart valve, severe calcified aortic stenosis (valve area \< 1.0 cm2), endocarditis, moderate to severe mitral stenosis, left atrial thrombus or any intracardiac mass or known paradoxical embolism of unrepaired PFO. 19. Unstable angina defined as rest angina with ECG changes that is not amenable to revascularization (patients should undergo planned coronary revascularization at least 30 days before randomization). 20. Any major surgery, major trauma, revascularization procedure or acute coronary syndrome within the past 1 month. 21. serum creatinine \>2.5 mg/dl or estimated GFR \<30 cc/min. 22. Major surgery planned within 3 months after enrollment. 23. Currently listed or being evaluated for major organ transplantation (i.e., heart, lung, liver and kidney). 24. Participation in other trials and may affect the results of this study. 25. Inability to understand and cooperate with research procedures or provide informed consent. 26. Endarterectomy, bypass or stent implantation performed on the proximal end of the occlusion vessel.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome | One year | The primary outcome was a composite of any stroke or death within 30 days after enrollment or ischemic stroke in the territory of the qualifying artery from 30 days to 1 year after enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality, mRS Score, NIHSS Score and Cognitive Function | t 30 days, 90 days, 8 months, 12 months and 24 months for both groups | to evaluate the change in all-cause mortality, mRS score, NIHSS score and cognitive function in the two groups |
| Incidence of Stroke/ TIA Ipsilateral to the Target Vessel | within 30 days and 90 days in both groups | stroke/ TIA ipsilateral to the target vessel will be defined according to the World |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Endovascular Recanalization Plus Standard Medical Treatment patients with symptomatic non-acute intracranial artery occlusion treated by endovascular recanalization and standard medical treatment after procedure
endovascular recanalization: to recanalize the occlusion cerebral artery with intravascular intervention | 154 |
| Standard Medical Treatment Patients take aspirin 100 mg/day or clopidogrel 75mg/day for the entire follow-up period (EVR patients take aspirin 100 mg/day and clopidogrel 75mg/day for 30-90 days after procedure)
endovascular recanalization: to recanalize the occlusion cerebral artery with intravascular intervention | 299 |
| Total | 453 |
Baseline characteristics
| Characteristic | Endovascular Recanalization Plus Standard Medical Treatment | Standard Medical Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 35 Participants | 81 Participants | 116 Participants |
| Age, Categorical Between 18 and 65 years | 113 Participants | 207 Participants | 320 Participants |
| Age, Continuous | 57 years | 58 years | 57 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 154 Participants | 299 Participants | 453 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 42 Participants | 72 Participants | 114 Participants |
| Sex: Female, Male Male | 106 Participants | 216 Participants | 322 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 148 | 5 / 288 |
| other Total, other adverse events | 0 / 148 | 0 / 288 |
| serious Total, serious adverse events | 9 / 148 | 0 / 288 |
Outcome results
Primary
Primary Outcome
The primary outcome was a composite of any stroke or death within 30 days after enrollment or ischemic stroke in the territory of the qualifying artery from 30 days to 1 year after enrollment.
Time frame: One year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Endovascular Recanalization Plus Standard Medical Treatment | Primary Outcome | 27 Participants |
| Standard Medical Treatment | Primary Outcome | 21 Participants |
Secondary
All-cause Mortality, mRS Score, NIHSS Score and Cognitive Function
to evaluate the change in all-cause mortality, mRS score, NIHSS score and cognitive function in the two groups
Time frame: t 30 days, 90 days, 8 months, 12 months and 24 months for both groups
Secondary
Incidence of Stroke/ TIA Ipsilateral to the Target Vessel
stroke/ TIA ipsilateral to the target vessel will be defined according to the World
Time frame: within 30 days and 90 days in both groups