Clinical trial NCT04864691: Endovascular Recanalization and Standard Medical Management for Symptomatic Nonacute Intracranial Artery Occlusion Trial
Official title: Department of Interventional Neurology, Beijing Tiantan Hospital, Capital Medical University
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Intracranial Artery Occlusion With Infarction
Keywords: standard medical therapy
symptomatic non-acute intracranial artery occlusion
endovascular recanalization
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2021-04-29
Enrollment: 453
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Primary Outcome
timeFrame: One year
Secondary outcomes:
measure: Incidence of Stroke/ TIA Ipsilateral to the Target Vessel
timeFrame: within 30 days and 90 days in both groups
measure: All-cause Mortality, mRS Score, NIHSS Score and Cognitive Function
timeFrame: t 30 days, 90 days, 8 months, 12 months and 24 months for both groups
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Anzhen Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing You 'anmen Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tiantan Hospital
state: Beijing
city: Beijing
country: China
facility: Liangxiang Hospital
state: Beijing
city: Handan
country: China
facility: Handan Central Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: Hebei Provincial People's Hospital
state: Hebei
city: Ordos
country: China
facility: ORDOS Central Hospital
state: Inner Mongolia Autonomous Region
city: TongLiao
country: China
facility: TongLiao City Hospital
state: Inner Mongolia
city: Jingjiang
country: China
facility: Jingjiang people's Hospital
state: Jiangsu
city: Dalian
country: China
facility: Dalian Municipal Central Hospital
state: Liaoning
city: Tai'an
country: China
facility: Tai'an Hospital of Traditional Chinese Medicine
state: Shandong
city: Shanghai
country: China
facility: Tong Ren Hospital Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Taiyuan Central Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Taizhou
country: China
facility: Taizhou first people's Hospital
state: Zhejiang
Study officials:
affiliation: Beijing Tiantan Hospital
name: feng feng, professor
role: STUDY_CHAIR
References:
citation: Zhang H, Han J, Sun X, Miao Z, Guo X, Xu G, Sun Y, Wen C, Wang C, Wu Y, Xu Y, Jiang Y, Zhang S, Liu C, Li D, Liu Y, Xu C, Gao F. Endovascular Recanalization and Standard Medical Management for Symptomatic Non-acute Intracranial Artery Occlusion: Study Protocol for a Non-randomized, 24-Month, Multicenter Study. Front Neurol. 2021 Sep 28;12:729534. doi: 10.3389/fneur.2021.729534. eCollection 2021.